Abstract:Therapeutic drug monitoring (TDM) is crucial for preserving vancomycin efficacy and avoiding adverse effects, and it is helpful to develop individualized dosing regimens. With the update of China and US criteria for TDM indexes, the TDM guided by the area under the 24 h drug-time curve (AUC_{24 h}) has gradually become a focus. Compared with trough concentration-guided TDM, AUC_{24 h}-guided TDM can decrease the incidence of vancomycin-induced acute kidney injury. Clinical implementation of AUC_{24 h}-guided TDM is possible using Bayesian and linear pharmacokinetic techniques. Both approaches can achieve AUC_{24 h} prediction and provide early intervention. It is essential for healthcare organizations to select appropriate methods of monitoring based on their actual situation.

Abstract:The immune system is characterized by complexity, diversity, and plasticity. Current research on the composition and dynamic changes of the immune system is limited to its population effects, and cannot fully reflect its heterogeneity. The emergence of single-cell technology has revolutionized our understanding of immunology. Single-cell RNA sequencing (scRNA-seq) is currently the most widely used single-cell technology, capable of analyzing a single cell or molecule to reveal the immune response under physiological or pathological conditions. This article provides a comprehensive review of the general process, development, and application of scRNA-seq in immunology, and discusses its future development in immunology.

Abstract:Melanoma is the most lethal type of malignant tumor among skin cancers. The mechanism of its development and progression is complex, and it is highly invasive, metastatic and lethal, with a poor prognosis. Therefore, it is particularly important to strengthen the basic research on this disease. Single-cell transcriptome sequencing, a rapidly developing new technology in recent years, has greatly promoted the basic and clinical research of melanoma with its unique advantages, such as exploring the heterogeneity of cellular subpopulations, identifying rare cells, and using bioinformatics algorithms to reveal the differentiation trajectories of different tissue and cells. This article reviews the progress in single-cell transcriptome sequencing studies of melanoma in terms of tumor heterogeneity and tumor immunity.

Abstract:Single-cell multiomics, involving various biological techniques for multifaceted analysis and research on a single cell to generate more comprehensive and accurate single-cell datasets, includes single-cell genomics, single-cell transcriptomics, single-cell proteomics, single-cell epigenetics, etc. Single-cell multiomics technology provides a more precise way to comprehend the complex cell types and functions, particularly for the more specialised cell types within the heterogeneous cell populations, such as stem cells or rare cancer cells, which have very important application value. By integrating information from different technologies, single-cell multiomics can more accurately characterise the state and changes of a single cell during multiple life events and processes, providing a more comprehensive and in-depth perspective for life science research. This article provides a systematic overview of the current representative single-cell multiomics technologies and summarizes their important application and potential in biological research.

Abstract:Pathology reveals the complex changes of biological tissue development, differentiation, maturation, and apoptosis from a micro perspective. Single-cell analysis technology provides more information for the study of complex system of pathology. Tumor is a complex ecosystem composed of tumor cells and their surrounding microenvironment. In pathology, the cells in tumors are different, with different distribution and physiological functions, and are regulated by themselves, their surrounding environment and treatment methods, forming a complex system. Using the causal determination method in complex systems, we can reveal the complex regulatory role of a single cell, and the causal relationships between different types of tumor cells and patient treatment regimens, treatment effects, recurrence, and survival time. Taking tumor as an example, in this article we expound the significance and research methods of single-cell pathology based on causality in complex systems.

Abstract:Objective To explore the relationships between peripheral blood inflammatory markers and acute ischemic stroke (AIS). Methods A total of 80 AIS patients in Neurovascular Center of The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Aug. to Dec. 2022 were enrolled. According to the National Institutes of Health stroke scale (NIHSS) score, the patients were categorized into mild AIS group (NIHSS＜4, n=50) or moderate-to-severe AIS group (NIHSS≥4, n=30). According to the 90-day modified Rankin scale (mRS) score, the patients were categorized into favorable outcome group (mRS 0-2, n=74) or unfavorable outcome group (mRS 3-6, n=6). The basic clinical data, peripheral blood inflammatory markers (including monocyte to lymphocyte ratio ［MLR］, neutrophil to lymphocyte ratio ［NLR］, platelet to lymphocyte ratio ［PLR］, systemic immune-inflammation index ［SII］, and systemic inflammatory response index ［SIRI］), and other laboratory data of the patients in each group were collected and compared. Results Compared with the mild AIS group, the moderate-to-severe AIS group had a significantly higher proportion of hyperlipidemia history (43.3% ［13/30］vs 18.0% ［9/50］, P=0.014) and significantly higher NLR (2.81 ［1.93, 5.97］ vs 2.01 ［1.64, 3.37］, P=0.028). Compared with the favorable outcome group, the unfavorable outcome group had a significantly higher proportion of hyperlipidemia history (83.3% ［5/6］ vs 23.0% ［17/74］, P=0.007), but there were no differences in MLR, NLR, PLR, SII, or SIRI (all P＞0.05). Conclusion Moderate-to-severe AIS patients have higher NLR.

Abstract:Objective To explore the expression levels of cytokines in serum of treatment-naive chronic hepatitis B (CHB) patients and its relationships with viral load and liver inflammation, so as to provide new ideas for dynamic assessment of disease and prognosis of CHB.Methods A total of 68 treatment-naive patients with chronic hepatitis B virus (HBV) infection, who were admitted to Department of Infectious Diseases of The First Hospital Affiliated to Naval Medical University (Second Military Medical University) from Oct. 2018 to Nov. 2019, and 12 healthy controls were enrolled. The expression levels of cytokines interleukin (IL)-17A, IL-2, IL-21, and IL-4 in serum were tested by enzyme-linked immunosorbent assay (ELISA). Chemiluminescence method was used to detect HBV serological markers, quantitative polymerase chain reaction (qPCR) was used to detect serum HBV DNA quantification, and automatic biochemical analyzer was used to detect liver function indexes. Spearman correlation analysis was used to evaluate the correlations of serum cytokines with viral load and degree of liver inflammation. Receiver operating characteristic (ROC) curves were drawn to evaluate the efficacy of serum cytokines in judging liver inflammation. Results Compared with the healthy controls, the serum IL-17A and IL-21 levels in the treatment-naive CHB patients were significantly higher (17.50 ［11.99, 25.36］ pg/mL vs 13.74 ［9.07, 16.94］ pg/mL, Z=-2.001, P=0.045; 37.12 (23.85, 77.66) pg/mL vs 20.30［17.9, 24.19］ pg/mL, Z=-3.485, P＜0.01), the IL-2 level was significantly lower (57.19 ［31.10, 79.92］ pg/mL vs 73.06 ［62.41, 105.84］ pg/mL, Z=-2.509, P=0.012), and there was no significant difference in IL-4 level (11.40 ［5.79, 18.62］ pg/mL vs 10.84 ［8.05, 25.20］ pg/mL;Z=-0.681, P=0.496). The expression levels of IL-17A in CHB patients with different disease courses were significantly different (H=8.870, P=0.031). Compared to the patients with inflammatory inactive CHB, the serum IL-17A and IL-21 levels were significantly higher (17.71 ［12.25, 27.92］ pg/mL vs 16.51 ［6.29, 20.22］ pg/mL and 39.29 ［24.71, 83.19］ pg/mL vs 25.06 ［19.37, 49.43］ pg/mL), the IL-2 level was significantly lower (57.19 ［31.10, 77.68］ pg/mL vs 71.24 ［48.07, 117.39］ pg/mL) (allP＜0.05), and there was no significant difference in IL-4 level (11.40 ［5.94, 18.12］ pg/mL vs 14.57 ［3.12, 24.49］ pg/mL,P＞0.05) in the patients with inflammatory active CHB. The levels of serum IL-17A (15.34 ［10.65, 25.04］, 19.98 ［15.55, 34.14］ pg/mL vs 13.74 ［9.07, 16.94］ pg/mL, H=10.061, P=0.007) and IL-21 (37.74 ［25.06, 82.87］, 51.74 ［23.32, 83.82］ pg/mL vs 20.30 ［17.90, 24.19］ pg/mL, H=12.444, P=0.002) in hepatitis B e antigen (HBeAg)-positive CHB patients and HBeAg-negative CHB patients were significantly higher than those in healthy controls, while the level of IL-2 (57.19 ［37.45, 79.92］, 37.45 ［18.32, 73.06］ pg/mL vs 73.06 ［62.41, 105.84］ pg/mL, H=6.576, P=0.037) was significantly lower than that in healthy controls. There were no correlations between serum IL-17A, IL-21, IL-4 levels and HBV DNA quantification in treatment-naive CHB patients (r=0.02, 0.23, 0.07, all P＞0.05), while the level of IL-2 was weakly correlated with HBV DNA quantification (r=0.32, P=0.01). There were correlations between serum IL-17A, IL-21 and alanine transaminase (ALT) (r=0.59, 0.49, both P＜0.01), aspartate transaminase (AST) (r=0.47, 0.36, both P＜0.01) in treatment-naive CHB patients, while IL-2 and IL-4 had no significant correlations with ALT or AST (all P＞0.05). There were statistically significant differences in serum levels of IL-17A, IL-2, and IL-21 among the treatment-naive CHB group with ALT≥300 U/L, the treatment-naive CHB group with ALT＜300 U/L, and healthy control group (all P＜0.05). Specifically, the levels of IL-17A and IL-21 in the treatment-naive CHB group with ALT≥300 U/L were significantly higher than those in the treatment-naive CHB group with ALT＜300 U/L and healthy control group (all P＜0.01). The level of IL-2 in the treatment-naive CHB group with ALT＜300 U/L was significantly lower than that in healthy control group, while the level of IL-21 was significantly higher than that in healthy control group (all P＜0.01). ROC curve analysis results showed that the area under curve (AUC) values of IL-17A and IL-21 to judge the degree of liver inflammation were 0.893 3 (95% confidence interval ［CI］ 0.793 0-0.993 6) and 0.760 0 (95% CI 0.622 7-0.897 3), respectively. Conclusion IL-17A, IL-2, and IL-21 are involved in the progression of chronic HBV infection. Regardless of whether HBeAg is positive or not or the degree of inflammation, the serum levels of IL-17A and IL-21 in the treatment-naive CHB patients are increased, while the level of IL-2 is decreased. IL-2 has a certain correlation with HBV DNA quantification. IL-17A and IL-21 are positively correlated with ALT and AST. Detection of IL-17A and IL-2 is helpful for disease assessment and prognosis.

Abstract:Objective To investigate the correlations of polymorphisms and mutations of osteoprotegerin (OPG) gene rs4355801 and rs6993813 loci with bone metabolism in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods From Oct. 2020 to Oct. 2021, 200 postmenopausal women who visited The First Affiliated Hospital of Shihezi University were enrolled and divided into normal glucose tolerance and bone mass group (group A, n=52), normal glucose tolerance but abnormal bone mass group (group B, n=43), T2DM with normal bone mass group (group C, n=47), and T2DM with abnormal bone mass group (group D, n=58). The baseline data such as age, height, weight, and years since menopause (YSM) were collected, and body mass index (BMI) and waist-hip ratio (WHR) were calculated. Biochemical indicators such as triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), blood calcium, blood phosphorus, alkaline phosphatase (ALP), and fasting blood glucose (FBG) were measured by Roche automatic biochemical analyzer. Glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography. Bone mineral densities (BMDs) of the lumbar spine (L_1-4) and neck of femur (NOF) were measured by dual energy X-rays. Polymorphism and genotyping of OPG gene rs4355801 and rs6993813 loci were determined by time-of-flight mass spectrometry. Multiple linear regression analysis was used to analyze the influencing factors of BMD. Linkage disequilibrium analysis and haplotype analysis of single nucleotide polymorphism loci were performed using SHEsis software. Results There were significant differences in age, BMI, and WHR among the 4 groups (P＜0.05). Compared with groups A and B, the levels of FPG and HbA1c in groups C and D were significantly increased (all P＜0.05). Compared with group B, the level of HDL-C in group C was significantly increased, while the level of ALP was significantly decreased (P＜0.05). Compared with group C, the level of ALP in group D was significantly increased (P＜0.05). The BMD (L_1-4) and BMD (NOF) in groups B and D were significantly decreased compared with groups A and C (all P＜0.05). The OPG gene rs4355801 and rs6993813 loci were in line with Hardy-Weinberg equilibrium. There were no significant differences between groups in rs4355801 genotype or allele frequency distribution (all P＞0.05). Compared with group A, there was a difference in rs6993813 genotype distribution in groups C and D (both P＜0.05), and there was no significant difference in allele frequency distribution among groups (all P＞0.05). The FPG and HbA1c levels of the patients with rs4355801 mutant type were both significantly lower than those with the wild type in group C (both P＜0.05). In group D, the BMD (L_1-4) of rs4355801 mutant type was significantly higher than that with the wild type (P＜0.05). The patients with rs6993813 mutant type in group D had significantly lower blood phosphorus levels and higher BMD (NOF) compared to the wild type (both P＜0.05). Multiple linear regression analysis showed that the increase of YSM and the decreases of BMI, TG, LDL-C, and HDL-C were the risk factors for the decrease of BMD (L_1-4); the increase of YSM and the decreases of HDL-C and blood phosphorus were the risk factors for the decrease of BMD (NOF); and rs4355801 AG genotype was a protective factor for the increases of BMD (L_1-4) and BMD (NOF) in postmenopausal women (both P＜0.05). There was no significant difference in BMD between wild-type and mutant rs4355801 or rs6993813 loci in postmenopausal women (both P＞0.05). There was a significant linkage disequilibrium relationship between the OPG gene rs4355801 and rs6993813 loci (D’＞0.9, r²＞0.3), and the risk of abnormal bone mass in postmenopausal women with GT haplotype was significantly higher (P＜0.05) and the risk of abnormal bone mass in postmenopausal women with AT haplotype was significantly lower (P＜0.05). The interactions of the OPG gene rs4355801 and rs6993813 loci had no effect on BMD in postmenopausal women (both P＞0.05). Conclusion OPG gene rs4355801 mutation may be involved in bone metabolism and glucose metabolism of postmenopausal women, and rs6993813 mutation and polymorphism are involved in bone metabolism of postmenopausal women. The significant linkage relationship of the OPG gene rs4355801 and rs6993813 loci may affect the BMD of postmenopausal women.

Abstract:Objective To analyze the status and focus of the research in the field of enteroscopy worldwide, so as to provide reference for researchers in the field of enteroscopy. Methods The year of publication “1998-2022”, the language “English”, the literature type “Article”, and the subject word “Enteroscopy” were used for retrieval in the Web of Science (WoS). VOSviewer 1.6.17 software and bibliometric online analysis platform (https://bibliometric.com) were used to analyze the included articles by countries, publishing institutions, authors and keywords, and to draw the corresponding visual knowledge graph. Results A total of 2 204 articles were included in the analysis. The top 3 countries with the highest number of publications in the field of enteroscopy were the United States, Japan, and China. Mayo Clin (69 articles), Assistance Publique Hopitaux Paris (AP-HP) (62 articles), and Udice French Research Universities (62 articles) were the top 3 terms of research institutions. The top 3 authors with the highest number of articles in the field of enteroscopy were Yamamoto (49 articles), Nakamura (42 articles), and Tanaka (40 articles). Yamamoto (frequency=1 688), Yano (frequency=1 514), and Tanaka (frequency=947) were highly cited authors in this field. In the keyword co-occurrence network, capsule endoscopy (frequency=625), enteroscopy (frequency=555), double-balloon enteroscopy (frequency=516), and diagnosis (frequency= 424) were high-frequency words in the field of enteroscopy. Conclusion In the past 20 years, the research in the field of enteroscopy has developed rapidly, and China’s role in the field of enteroscopy has gradually improved in the world. Capsule endoscopy and enteroscopy for the diagnosis and treatment of intestinal diseases has been a research focus.

Abstract:Chronic pancreatitis is usually manifested as partial or diffuse progressive inflammation of the pancreas, frequently causing symptoms like persistent abdominal pain and secondary exocrine and endocrine pancreatic insufficiency. It has become a vital public health problem in most countries around the world. From the 1940 s to the end of the 20^th century, the incidence and prevalence of chronic pancreatitis showed an overall upward trend in the world. After 2000, the incidence and prevalence of chronic pancreatitis tended to be stable or showed a downward trend in a few developed countries. This article reviews the global status of epidemiological research on chronic pancreatitis and the causes for its differentiation.

Abstract:Ferroptosis is a unique way of regulated cell death characterized by iron-dependent and excessive accumulation of lipid peroxides. It is greatly different from apoptosis, necrosis, autophagy, and other forms of cell death in morphology, biology, and genetics. The metabolism of iron, lipid and amino acid and other signaling pathways are closely related to ferroptosis. It is closely associated with the pathological processes of diseases such as cancer, inflammation, neurodegeneration, liver and kidney injury, and ischemia/reperfusion injury. Acute respiratory distress syndrome (ARDS) is an inflammatory disease of the lung that seriously threatens human life and health with high incidence and mortality. The pathways involved in lung injury pathogenesis and repair have been broadened in recent years. Therapies targeting ventilation-induced lung injury have consistently proven beneficial for ARDS patients, but there is still a lack of effective drug treatment. The global pandemic of the coronavirus disease 2019 has made ARDS even more severe. It is urgent to further explore its mechanism at cellular and molecular levels and develop new therapies. This article reviews the definition and mechanism of ferroptosis and its role in ARDS from basic to clinics.

Abstract:Mangiferin is a naturally derived C-glucosyl flavone, which can be isolated from many plants as a potent pharmaceutical compound. Previous studies indicated that mangiferin exerts an array of pharmacological activities, including anti-diabetes, anti-tumor, anti-inflammation, anti-oxidation, treatment of eye diseases, nervous system protection, kidney protection, and improvement of cardiovascular diseases. Due to its various biological activities, mangiferin has great potential for prevention and treatment of many diseases. This paper summarizes the research progress and the mechanism of mangiferin pharmacodynamics, so as to provide a scientific basis for the further research and utilization of mangiferin.

Abstract:Objective To explore the relationship among the mental health status and ease of excitation, mental resilience and coping tendency of officers and soldiers in a certain naval unit, and to elucidate the possible mechanisms by which ease of excitation affects mental health. Methods The self-reporting questionnaire 20 (SRQ-20), connor-davidson resilience scale, highly sensitive person scale (HSP-10), and simplified coping style questionnaire (SCSQ) were used to survey 1 870 officers and soldiers of a certain naval unit. Spearman correlation method was used to verify the correlations between variables, multiple stepwise regression analysis was used to predict the effects of ease of excitation, mental resilience and coping tendencies on mental health status, and a structural equation model was constructed to explore the mediating roles of mental resilience and coping style between ease of excitation and mental health status. Results The score of SRQ-20 was 1 (0, 5), and the positive rate was 21.2% (395/1 865). Correlation analysis showed that mental health status of officers and soldiers was positively correlated with ease of excitation (P＜0.01), and was negatively correlated with the aesthetic sensitivity, mental resilience, and coping tendency (all P＜0.01). Multiple regression analysis showed that ease of excitation, mental resilience, and coping tendency had predictive effects on mental health, and mental resilience and coping tendency played partial chain mediating roles between ease of excitation and mental health. Conclusion The ease of excitation of officers and soldiers in the certain naval unit can directly predict their mental health status, and the independent and chain mediating effects of mental resilience and coping tendency can also indirectly predict their mental health status.

Abstract:Objective To establish and verify a liquid chromatography-mass spectrometry (LC-MS) method for the determination of 3 residual chloramphenicols in the urine of pregnant women.Methods Urine was purified and concentrated by Oasis HLB solid phase extraction column, and liquid phase separation was performed on a SHISEIDO MG-C₁₈ (100 mm× 3.0 mm, 3.0 μm) column with mobile phase of acetonitrile-water (containing 0.1% formic acid) for gradient elution. Electrospray ionization source was used for MS, and ion monitoring mode was selected for detection ［M-H］^-: chloramphenicol m/z 320.8, florfenicol m/z 355.8, thiamphnicol m/z 353.8, and sulfonamide (internal standard) m/z 268.9. Results The 3 residual chloramphenicols in urine showed a good linear relationship in the range of 5-500 ng/mL (all r＞0.999); the precision and accuracy within and between batches were good (relative standard deviation＜8.9%, ∣relative error ［RE］∣＜9.3%); the extraction recoveries ranged from 71.4% to 108.5%, with good stability (∣RE∣＜11.8%), almost with no residue; dilution did not affect the precision and accuracy of the determination. A total of 18 urine samples from pregnant women of different trimesters (first trimester, second trimester, and third trimester) were tested, chloramphenicol was detected in most of the samples (but the concentration was below the minimum quantitation limit of 5 ng/mL), florfenicol was detected in a few samples, and no thiamphnicol residue was detected at all. Conclusion The present method is simple, reproducible and suitable for the determination of 3 kinds of chloramphenicols in urine. It can provide a methodological basis for the study of the correlation between chloramphenicol residues and adverse pregnancy outcomes of pregnant women.

Abstract:Objective To investigate the clinical effect of “three-in-one” bone repair strategy in the treatment of osteoporotic proximal humeral fractures in elderly patients. Methods A retrospective case-control study was conducted to analyze the clinical data of 28 elderly osteoporotic patients with proximal humeral fractures treated with “three-in-one” bone repair strategy in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from Apr. 2019 to May 2020. The fracture healing time and neck-trunk angle were recorded. At the last follow-up, shoulder function was evaluated by the University of California Los Angeles (UCLA) shoulder score, bilateral range of motion and complications were observed as well. Results There were 8 males and 20 females, aged 65-86 (71.7±6.0) years. There were 10 patients with Neer’s two-part fracture, 14 three-part fracture, and 4 four-part fracture. All patients were followed up for 9-12 months, with an average of 10.5 months. Bone union was achieved in 28 patients with a mean healing time of (12.6±1.5) weeks and a mean cervix-trunk angle of (133.1±5.6)°. The average UCLA shoulder score was (31.1±4.1). The mean uplift, abduction, and external rotation angles of the injured side shoulder joint were (132.5±7.7)°, (116.5±7.0)°, and (40.3±3.5)°, and the internal rotation reached L_2/3. The mean uplift, abduction, and external rotation angles of the healthy side shoulder joint were (169.5±7.3)°, (157.5±6.9)°, and (52.1±4.2)°, and the internal rotation reached T_11/12. The difference of range of motion between the 2 sides was statistically significant (P＜0.05). Screw cut-out occurred in 1 patient, with a complication rate of 3.6%. Conclusion For the elderly patients with osteoporotic proximal humeral fracture, “three-in-one” bone repair strategy shows high bone union rate, low surgical complication rate, good recovery of shoulder joint function, and satisfied clinical results.

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