Abstract:Many genomic features of lymphohematopoietic tissue tumors have been recognized by molecular pathological testing and high-throughput sequencing technology. The gene detection technology and its progress are of great significance for the diagnosis and treatment of lymphoma. This paper introduces new technologies for the pathological diagnosis and research of lymphoma, including whole genome sequencing, circulating tumor DNA analysis, single cell analysis and epigenetic research, etc. The latest progress in the genetic characteristics, prognostic stratification and treatment prospects of common lymphoma based on the new WHO classification of lymphohematopoietic tissue tumors will help to guide the pathological diagnosis and clinical treatment of lymphoma.

Abstract:Hepatocellular carcinoma (HCC) still has a poor clinical prognosis, mainly due to its insidious onset, and most patients have reached an advanced stage at initial diagnosis and lost the indications for surgery. With the combined application of multidimensional therapeutic options such as novel targeted drugs, immune drugs and local therapies, the objective response rate of HCC has greatly improved, laying a foundation for conversion therapy. Conversion therapy is a major breakthrough for the treatment of HCC lately, and it aims to make unresectable tumors resectable, and has now become an effective treatment for unresectable HCC. However, conversion therapy of HCC still faces many challenges. The paper provides an in-depth description of the strategies and efficacy of conversion therapy for HCC based on the authors’ clinical experience and the latest advances in this field.

Abstract:Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, and its incidence and mortality are among the highest for many years. Due to its insidious onset, most patients are already at advanced stages when diagnosed. Improving the prognosis and survival rate of patients through conversion therapy has become a research focus lately. In recent years, with the continuous progress of biotechnology and drug development, new therapies represented by targeted and immunotherapy drugs have been widely used in HCC conversion therapy. Compared with other conversion therapy regimens, these drugs can effectively prolong the progression free survival and overall survival of patients and have advantages such as controllable adverse reactions. In addition, the combination of targeted drugs and immunotherapy drugs also plays a positive role in improving the survival benefit of HCC patients. This article aims to review the latest research progress of targeted therapy and immunotherapy in the first- and second-line treatments of HCC, and to discuss their safety and future development.

Abstract:The biological characteristics of hepatocellular carcinoma (HCC) lead to a high incidence of portal vein tumor thrombus. It progresses rapidly, and the opportunity for radical surgical resection can be lost in a short term, resulting in poor prognosis. Reasonable down-staging treatment is a research focus for patients with unresectable HCC complicated with portal vein tumor thrombus to achieve a resectable range. This article reviews the potential population of HCC complicated with portal vein tumor thrombus with conversion therapy for HCC, analyzes the application of hepatic artery infusion chemotherapy, transcatheter arterial chemoembolization, radiotherapy, regional and systemic drug therapy in conversion therapy, and points out that the combination of multidisciplinary comprehensive treatments is the key to improve the prognosis of HCC patients with portal vein tumor thrombus.

Abstract:Yttrium-90 (⁹⁰Y) selective internal radiation therapy (SIRT) is an emerging modality for the treatment of hepatocellular carcinoma (HCC), leveraging the nuclide ⁹⁰Y to deliver targeted radiation therapy. ⁹⁰Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays. It has high biological effectiveness and robust local control capabilities. In recent years, with the continuous advancement of basic and clinical research, the application of ⁹⁰Y-SIRT in the conversion treatment of unresectable HCC (uHCC) has made significant progress. However, challenges remain in the clinical application of ⁹⁰Y-SIRT, including how to improve the efficacy of conversion therapy and how to optimize therapy regimens. This review aims to summarize the research progress of ⁹⁰Y-SIRT in the conversion therapy of uHCC.

Abstract:Objective To explore the efficacy and safety of conversion therapy for advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods A total of 149 patients with advanced HCC with macrovascular invasion who were treated at our hospital from Jul. 2019 to Jun. 2021 were enrolled. All patients received systemic therapy combined with local therapy, and were assigned to conversion therapy group (n＝42) and non-conversion therapy group (n＝107) according to whether they ultimately underwent surgical treatment. The long-term prognosis and adverse reactions of these patients after conversion therapy were analyzed. Results The median event-free survival of 149 patients was 15.5 months, and the median overall survival had not been reached. The median event-free survival in the conversion therapy and non-conversion therapy groups were 19.8 months and 10.7 months, respectively, with the median overall survival being not reached and 28.2 months, respectively. Multifactor Cox regression analysis showed that conversion therapy was a protective factor for overall survival (hazard ratio ［HR］ ＝0.125, 95% confidence interval ［CI］ 0.016-0.966), but not for event-free survival. The 1-year and 2-year overall survival rates of the conversion therapy and non-conversion therapy groups were 100.0%, 96.4% and 72.1%, 53.4%, respectively, and the difference in survival curves between the 2 groups was statistically significant (P＝0.003). The 1-year and 2-year event-free survival rates were 77.5%, 33.8% and 47.3%, 31.5%, respectively. There was no significant difference in survival curves between the 2 groups (P＝0.070). The differences of the overall incidences of targeted and immunotherapy-related adverse reactions in the conversion therapy group and non-conversion therapy group (66.7% ［28/42］ vs 72.0% ［77/107］, P＝0.524) and the incidences of grade Ⅲ to Ⅳ adverse reactions (23.8% ［10/42］ vs 27.1% ［29/107］, P＝0.681), were not statistically significant. Conclusion For patients with advanced HCC with macrovascular invasion, conversion therapy can significantly improve the prognosis without serious adverse reactions.

Abstract:Objective To explore the perioperative safety and prognostic factors of sequential hepatectomy after conversion therapy using vascular interventional therapy (including transarterial chemoembolization and hepatic arterial infusion chemotherapy) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma. Methods The clinical data of 106 eligible HCC patients treated in Tumor Hospital Affiliated to Guangxi Medical University from Nov. 2019 to Apr. 2024 were retrospectively analyzed. The perioperative parameters and postoperative pathological outcomes were described in detail, and factors influencing prognosis were analyzed. Results The median operative time for hepatectomy after conversion therapy was 240 min, with a median blood loss of 200 mL. Intraoperative blood transfusion was required in 24 (22.6%) patients. Postoperative adverse reactions occurred in 49.1% (52/106) of patients, with liver failure being the most common adverse reactions (23 patients, 21.7%). One (0.9%) patient died during the perioperative period, while the remaining 105 patients were followed up for a median duration of 14.7 months, during which 49 (46.2%) patients experienced recurrence. Among them, 39 (36.8%) cases experienced early recurrence (within 1 year), and 33 (31.1%) cases had intrahepatic recurrence. Thirteen (12.3%) patients died during follow-up. The median recurrence-free survival (RFS) was 15.7 months, with 1-year and 2-year RFS rates being 56.9% and 40.3%, respectively. The median overall survival (OS) was not reached, with 1-year and 2-year OS rates being 94.2% and 85.3%, respectively. Multivariate Cox regression analysis demonstrated that achieving complete pathological response (hazard ratio ［HR］ ＝0.410, 95% confidence interval ［CI］ 0.172-0.980, P＝0.045), presence of microvascular invasion (HR＝2.423, 95% CI 1.269-4.625, P＝0.007), satellite nodules (HR＝1.916, 95% CI 1.014-3.620, P＝0.045), and multiple tumors (HR＝1.818, 95% CI 1.012-3.241, P＝0.046) were independent factors associated with postoperative recurrence. Conclusion For patients with initially unresectable hepatocellular carcinoma, vascular interventional therapy combined with TKI and PD-1 inhibitors followed by sequential hepatectomy may be a feasible treatment strategy, with manageable adverse reactions and promising efficacy.

Abstract:Objective To investigate the relationship between the expression of nuclear factor ⅠB (NFIB) in myeloid cells and intestinal inflammation by constructing NFIB conditional gene knockout (cKO) mice. Methods Human Protein Atlas database, Genotype-Tissue Expression database, and FANTOM5 database were used to investigate the expression of NFIB in inflammatory cells. NFIB-floxed mice were constructed using CRISPR/Cas9 technology and hybridized with LyZ2-Cre transgenic mice. Myeloid specific NFIB cKO mice (NFIB^fl/flLyz2-Cre) were obtained by self-crossing the progeny. After the genotype identification of mice by agarose gel electrophoresis, 4 NFIB cKO mice of C57BL/6N strain were selected as experimental group, and 4 non-cKO mice were selected as control group. Both groups were induced with 2.5% dextran sulfate sodium salt (DSS) under the same condition to establish a chronic colitis model, and the severity of colitis was evaluated by clinical manifestations and histopathology. Results Analysis showed that NFIB was expressed in both myeloid granulocytes and monocytes, and the highest expression was found in neutrophils. NFIB cKO mice were successfully constructed using CRISPR/Cas9 technology and Cre-loxP system. DSS-induced enteritis NFIB cKO mice developed diarrhea, gross blood stools, reduced activity, and weight loss in a short time. The gross examination of the intestines showed that the colon of the NFIB cKO mice was significantly shorter than that of the non-cKO mice (［8.23±0.35］ cm vs ［10.30±0.36］ cm, P＜0.01). Intestinal H-E staining showed changes in mucosal glandular structure and connective tissue hyperplasia with extensive inflammatory cell infiltration in NFIB cKO mice. The histological score of NFIB cKO mice was significantly higher than that of non-cKO mice (4.25±0.50 vs 0.50±0.58, P＜0.01). Intestinal immunohistochemical staining showed that more CD11b positive cells were recruited in NFIB cKO mice than non-cKO mice. Conclusion Myeloid specific NFIB cKO mice have been successfully constructed, and NFIB in myeloid cells can reduce infiltration of immune cells (granulocytes or/and monocytes) to inhibit intestinal inflammation.

Abstract:Objective To investigate the accuracy of prostate imaging and reporting data system (PI-RADS) score in diagnosing prostate cancer (PCa) with different prostate-specific antigen (PSA) levels. Methods Patients who underwent multiparametric magnetic resonance imaging scanning with biopsy of the prostate to obtain pathological confirmation in The First Affiliated Hospital of Naval Medical University (Second Military Medical University) between Jan. 2017 and Jun. 2023 were enrolled, and serum total PSA (t-PSA), free PSA (f-PSA), the ratio of free PSA to total PSA (f/t PSA) and PI-RADS scores were summarized in all patients. The accuracy of PI-RADS score in diagnosing PCa was analyzed at different PSA levels using pathology of the prostate biopsy as the gold standard. Results A total of 2 526 patients were enrolled and categorized into 7 groups according to the PSA level: 0-4 ng/mL, ＞4-10 ng/mL (f/t PSA≥0.16), ＞4-10 ng/mL (f/t PSA＜ 0.16), ＞10-20 ng/mL, ＞20-50 ng/mL, ＞50-100 ng/mL, and ＞100 ng/mL. In all patients, the sensitivity of PI-RADS≥3 in diagnosing PCa was 90.0%, which was superior to PI-RADS≥4 (sensitivity: 76.3%). Among the patients with PSA≤4 ng/mL, the accuracy of PI-RADS≥4 in diagnosing PCa was higher than that of PI-RADS≥3 (87.7% vs 64.0%). With the increase of PSA levels, the diagnostic accuracies of PI-RADS≥4 and PI-RADS≥3 were gradually increased and tended to be the same. When PSA was ＞50-100 ng/mL, the diagnostic accuracies of PI-RADS≥4 and ≥3 were 90.7% and 92.0%, respectively. Conclusion At higher PSA levels, the accuracies of PI-RADS scores in diagnosing PCa are higher, which can reduce unnecessary puncture of patients.

Abstract:Objective To analyze the incidence and mortality of prostate cancer (PCa) in the world and China based on the data of 2022 global cancer statistics published by the World Health Organization (WHO). Methods Based on the data of 2022 global cancer statistics, the number of incident cases, crude incidence, standardized incidence rate (SIR), number of deaths, crude mortality, and standardized mortality rate (SMR) of PCa in the world and China were systematically described, and stratified according to the age and human development index (HDI). Pearson correlation analysis was applied to evaluate the correlations of SIR, SMR, and mortality-to-incidence ratio (M/I) with HDI. Results In 2022, there were 1 467 000 new cases of PCa in the world, with an SIR of 29.4/100 000, ranking the 2^nd among all cancer types in the males; the number of deaths in the world was 397 000, with an SMR of 7.3/100 000, ranking the 5^th among all cancer types in males. In 2022, the number of new PCa cases in China was 134 000, with an SIR of 9.7/100 000 and an SMR of 3.3/100 000, both ranking the 7^th among males. The number of new PCa cases and SIR in the world increased rapidly from 45 years of age, and the number of deaths and SMR showed a rapid growth trend from 50 years of age; the number of new PCa cases and SIR in China increased rapidly from 60 years of age, and the number of deaths and SMR increased rapidly from 65 years of age. The M/I of PCa in China was 0.337, ranking the 30^th among countries and territories with high HDI. Pearson correlation analysis showed that SIR was positively correlated with HDI (r＝0.440, P＝0.008), M/I were negatively correlated with HDI (r＝－0.877, P＜0.001), while SMR was not correlated with HDI (P＞0.05). Conclusion The burden of PCa is heavy in the world. The incidence of PCa in China is gradually increasing, and it is characterized by high mortality. Actively carrying out early screening of PCa, optimizing the diagnosis and treatment mode with multidisciplinary collaboration, and achieving the whole process management can improve the diagnosis, treatment and prognosis of patients.

Abstract:Chronic obstructive pulmonary disease (COPD) is one of the most common chronic lung diseases, which is characterized by chronic irreversible airway obstruction. Chronic airflow restriction causes a decrease in oxygen supply to the brain, which inevitably leads to a series of changes in brain function and structure. In recent years, many magnetic resonance imaging (MRI) technology has been applied to explore the brain function and structure of COPD. Resting-state functional MRI, voxel-based morphometry, and diffusion tensor imaging are reviewed in this article to discuss the recent research progress of brain function and structure imaging study in COPD.

Abstract:Atrial fibrillation is one of the most common arrhythmias; its high incidence rate and high disability rate lead to heavy social and economic burdens. Most atrial fibrillation originates from pulmonary veins, so pulmonary vein isolation is the mainstay of catheter ablation for the treatment of atrial fibrillation. Cryoballoon ablation has the advantages of reversible injury, short operation time, and better surgical experience for patients. At present, it has been widely used in clinical practice and has become the first-line treatment scheme for atrial fibrillation. However, compared with radiofrequency ablation, cryoballoon ablation carries a relatively higher risk of causing phrenic nerve injury, particularly during the process of cryoablation targeting the right pulmonary vein. Therefore, this article aims to discuss the strategies for preventing phrenic nerve injury during cryoballoon ablation for atrial fibrillation, such as the temperature monitoring during cryoablation and the strategies of balloon operation (i.e. balloon deflation, proximal occlusion, phrenic nerve pacing), so as to summarize the experience and effectively prevent complications.

Abstract:Esophageal cancer is one of the common malignant tumors, and its incidence in China is high. Effective prevention and control is a focus and challenge due to difficult prevention and late diagnosis. The development of liquid biopsy technology represented by circulating tumor DNA (ctDNA) provides new insights for early diagnosis, treatment evaluation and prognosis monitoring of esophageal cancer. ctDNA detection method has high specificity and sensitivity, which can be used in tumor screening and diagnosis, and has high application value in judging prognosis and guiding treatment. This article reviews the detection technology of ctDNA and the research progress in the diagnosis and treatment of esophageal cancer.

Abstract:Objective To evaluate and improve missing data imputation methods to enhance the performance of binary classification prediction model. Methods By simulating data missing scenes, the effects of direct elimination, mean imputation, random forest (RF) imputation algorithm, and multiple imputation-random forest (MI-RF) on the performance of the prediction model were jointly evaluated by receiver operating characteristic area under curve (AUC) and root mean square error (RMSE). Bayesian Network was introduced for the random forest imputation algorithm to optimize the imputation method using the correlations between variables. Results Under different missing proportions, both AUC and RMSE indicated that Bayesian network optimized random forest (BN-RF) imputation algorithm was better. In addition, when the missing proportion was 10%-20%, various imputation methods had roughly the same improvement effect for the prediction model; when the proportion of missing data was 30%-40%, compared to the mean imputation, except for the BN-RF, RF was more effective and its effect was slightly better than MI-RF; however, when the proportion of missing data was close to 50%, even if the model performance was still appropriate, the imputation data gradually deviated from the true data features, resulting in a decrease in the usability of the model. Conclusion The overall effect of BN-RF is satisfactory, and it should be chosen when random missing was 30%-40%.

Abstract:Self-aid and buddy-aid are primary steps in battlefield first aid, offering the timeliest treatment effectiveness. Medications are indispensable key supplies in battlefield first aid, playing a crucial role in the timely treatment of the injured. This review provides an overview of medication preparation for battlefield first aid both domestically and internationally, aiming to provide reference for the medication preparation for self-aid and buddy-aid of naval combat injuries, so as to enhance the Navy’s first-aid capability and medical support capability.

Abstract:Objective To analyze the influencing factors of cholecystolithiasis among Tibetan residents living at extreme altitude. Methods From Aug. 10 to 17, 2023, Nima County People’s Hospital in Nagqu, in collaboration with Tibetan-aid doctors, organized physical examinations for Tibetan residents in Jiwa Township. The physical examination data were collected, and the general information and dietary habits of the examinees were recorded. Based on the results of abdominal ultrasound examination, the 448 enrolled participants were assigned to a cholecystolithiasis group (106 cases) and a non-cholecystolithiasis group (342 cases). Additionally, multivariable logistic regression analysis was conducted to investigate the factors influencing the occurrence of cholecystolithiasis among Tibetan residents. Results There were significant differences in age, weight, body mass index, systolic blood pressure, diastolic blood pressure, finger pulse oxygen, and educational level between the 2 groups (all P＜0.05). The results of multivariate logistic regression analysis showed that age (odds ratio ［OR］ ＝1.062, 95% confidence interval ［CI］ 1.020-1.106), weight (OR＝1.120, 95% CI 1.067-1.176), smoking (OR＝4.751, 95% CI 1.627-13.869), cholesterol (OR＝1.429, 95% CI 1.129-1.810), amount of butter tea drink (OR＝2.123, 95% CI 1.656-2.721), alanine transaminase (OR＝1.045, 95% CI 1.028-1.062), low educational level (OR＝6.994, 95% CI 2.615-18.702), fatty liver (OR＝4.409, 95% CI 1.499-12.968) and meat-based diet (OR＝3.725, 95% CI 1.255-11.055) were correlated with cholecystolithiasis. Conclusion The incidence of cholecystolithiasis among Tibetan residents living at extreme altitude may be related to various factors mentioned above, which provides clues for the prevention, early diagnosis, and treatment of local cholecystolithiasis.

Abstract:Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of ginsenoside Rh2 (GRh2) in plasma of mice, so as to provide preclinical data support for the pharmacokinetic study and application of GRh2. Methods C57BL16 mice were given 7.5 mg/kg GRh2 by gavage. After administration, 0.03 mL of whole blood was collected at 5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h. Then, the whole blood was centrifuged and the serum was treated with 0.1% formic acid acetonitrile, dried by nitrogen (40 ℃), and redissolved with 50.0 μL 50% methanol solution containing 100 ng/mL diclofenac sodium. After vortex mixing for 5 min at room temperature, it was put into the automatic sampler for sampling analysis. The chromatographic column was Waters BEHC₁₈ (2.1 mm×50.0 mm, 1.7 μm), the mobile phase was aqueous solution containing 0.1% formic acid and acetonitrile solution containing 0.1% formic acid at a flow rate of 0.60 mL/min, the column temperature was 40 ℃, and the injection volume was 1.00 μL. The electric spray ion source, positive ion mode and multiple reaction monitoring mode were performed. A standard curve was established to calculate blood drug concentration. The blood drug concentration-time curve was established according to the blood drug concentration, and the main pharmacokinetic parameters were calculated. Results The linear range of the standard curve of drug containing plasma was 100-40 000 ng/mL, and the correlation coefficient (r) was 0.996 0. After internal standard normalization, the matrix effect factors of GRh2 were 1.09, 1.06, and 1.00 (between 0.8 and 1.2), indicating no significant matrix effect. The precision and accuracy results showed that the average measured concentration of GRh2 samples at each concentration level was 103, 333, 23 800 and 35 000 ng/mL, the inter batch standard deviation was 6.47-1 120 ng/mL, the inter batch relative standard deviation was 1.5%-8.3%, and the inter batch accuracy deviation was 93.3%-111.1%. The long-term stability, short-term stability, repeated freeze-thaw property, and extraction recovery rate of GRh2 were all good. The pharmacokinetic parameters T_max and C_max of GRh2 in mice were (1.42±1.01) h and (1 251±495) ng/mL, respectively, indicating that the absorption and utilization rate of GRh2 in vivo was high and GRh2 had good drug performance. Conclusion The established LC-MS/MS method is accurate and reliable, and can be used to determine the concentration of GRh2 in mouse plasma and study its pharmacokinetic.

Abstract:

Abstract: