ObjectiveTo observe the therapeutic effect of Shugan Huazheng prescription on hepatic fibrosis model rats induced by carbon tetrachloride （CCl₄） and explore whether it plays its role through hypoxia-induced factor-1α/vascular endothelial growth factor/transforming growth factor-β₁ （HIF-1α/VEGF/TGF-β₁） pathway. MethodA total of 54 male SPF SD rats were randomly divided into six groups： blank group， model group， colchicine group （0.2 mg·kg^-1）， and high-， medium-， and low-dose groups （29.52， 14.76， and 7.38 g·kg^-1） of Shugan Huazheng prescription， with nine rats in each group. The molding was conducted three times a week for eight weeks. Administration began the day after the first injection， and the drug intervention was once a day for eight weeks. On the day after the last administration， the rats were deprived of food and water， and they were killed the next day， during which the physiological status of each group of rats was dynamically monitored. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining， and the content of hydroxyproline （HYP） and angiotensin Ⅱ （AngⅡ） in liver tissue were detected by enzyme-related immunosorbent assay （ELISA）. Real-time fluorescent quantitative PCR （Real-time PCR） was used to determine the mRNA expression levels of HIF-1α， VEGF， and TGF-β₁ in liver tissue， and immunohistochemical method （IHC） and Western blot were used to detect the protein expression levels of HIF-1α， VEGF， and TGF-β₁ in liver tissue. ResultCompared with the blank group， the overall condition of rats in the model group decreased significantly. The proliferation of connective tissue and the increase in adipose cells between hepatocytes were obvious. The content of HYP and Ang was increased. The mRNA and protein expressions of HIF-1α， VEGF， and TGF-β₁ were increased to varying degrees （P<0.05）. Compared with the model group， the proliferation of connective tissue and inflammatory cell infiltration in the liver tissue of colchicine and Shugan Huazheng prescription groups were reduced. The content of HYP and Ang was decreased. The mRNA and protein expression levels of HIF-1α， VEGF， and TGF-β₁ were decreased， and the colchicine group and high-dose group of Shugan Huazheng prescription were the most significant （P<0.05）. ConclusionShugan Huazheng prescription has an obvious therapeutic effect on CCl₄-induced hepatic fibrosis model rats. Its therapeutic mechanism may be related to the regulation of the HIF-1α/VEGF/TGF-β₁ signaling pathway and the improvement of hepatic hypoxia， vascular remodeling， and the syndrome of Qi deficiency and blood stasis in hepatic fibrosis.

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction pro-cesses,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tu-mors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

Objective Sequencing depth is a key parameter in next generation sequencing,which is closely related to the accuracy of sequencing results.Forensic biological evidence examination requires extremely high accuracy.It is crucial to scientifically and reasonably set the sequencing depth analysis threshold for forensic next generation sequencing testing.Methods This study used targeted sequencing data of microhaplotypes from 50 samples with known genotypes.By calculating the accuracy,precision,recall,and F1 score of each locus under various threshold conditions,two types of analysis threshold setting methods,which were based on fixed read count and fixed sequencing depth ratio,were studied extensively.Results The results showed that false positives were observed when the analysis threshold was set at 50×or 100×.When the analysis threshold was set at 200×,false negatives were observed.When the analysis threshold was set at 1.5%,3.0%,or 4.5%,false positives were observed.This study further proposed a third type of analysis threshold setting method,which was based on sequencing depth ratio scatter plots.With this method,no false positive or false negative was observed in the results.This article then explored four factors that lead to significant differences in the sequencing depth of forensic next generation sequencing experiments,compared with the analysis threshold setting method for capillary electrophoresis technology,and discussed the correlation between analysis thresholds and the ability to distinguish mixed DNA.Conclusion Employing the sequencing depth ratio scatter plot method to set analysis threshold has significant application value in next generation sequencing-based forensic genetic marker genotyping.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.

Objective To investigate the therapeutic effect of Shugan Heluo Xingpi Decoction on CCl 4 -induced liver fibrosis in rats, and the underlying molecular mechanism. Methods Sixty male SPF Wistar rats were randomly assigned to six groups: blank control, model, positive control, high, medium or low dose groups of Shugan Heluo Xingpi Decoction ( n =10 per group). The liver fibrosis rat model was induced by an intraperitoneal injection of 40% CCl 4 oil solution. Rats in the blank control and model groups were administered 10 mL/kg normal saline by gavage, rats in the positive control group were administered 50 mg/kg silibinin meglumine by gavage, while rats in high-dose, medium-dose and low-dose groups of Shugan Heluo Xingpi Decoction were administered 12.42 g/kg, 6.21 g/kg and 3.11 g/kg (crude drug/body weight) by gavage, respectively, daily for 8 weeks. Rats was sacrificed after 8 weeks, during which the physiological status of rats in each group was dynamically monitored. Following sacrifice, serum was collected to detect HYP using alkaline hydrolysis colorimetry and the expression levels of AST, ALT, total protein (TP), and Alb using an automatic biochemical analyzer. The pathological morphological changes in the liver were detected by H & E staining and Masson staining, and the mRNA and protein levels of Wnt1, β-Catenin and Cyclin D1 were detected by RT-qPCR and Western Blot. Measurement data were compared across groups using one-way ANOVA with post-hoc LSD- t test. Results Compared with the model group, after silibinin meglumine and Shugan Heluo Xingpi Decoction intervention, the physiological status of rats was significantly improved; serum levels of HYP, ALT, AST and Glo were significantly decreased, while serum levels of TP, Alb and A/G were significantly increased (all P < 0.05). Compared with the positive control group, serum levels of ALT and AST were significantly increased (all P < 0.05), while the levels of TP, Alb and A/G were significantly decreased (all P < 0.05) in low-dose group of Shugan Heluo Xingpi Decoction. H&E staining showed mild portal vein fibrosis with a few fibrous septa and mild steatosis of hepatocytes in the positive control group, obvious portal vein fibrosis with a few fiber septum in the low dose group, a few portal vein fibrosis in the medium dose group, while no obvious abnormality in the high dose group of Shugan Heluo Xingpi Decoction. Masson staining revealed that the therapeutic effect of high dose group of Shugan Heluo Xingpi Decoction on collagen deposition was superior to silibinin meglumine and medium and low dose of Shugan Heluo Xingpi Decoction (all P < 0.05), and was generally equivalent to high dose of Shugan Heluo Xingpi Decoction. Silibinin meglumine and medium and high doses of Shugan Heluo Xingpi Decoction inhibited more significantly the mRNA and protein expression of Wnt1, β-catenin and Cyclin D1 (all P < 0.05). Conclusion Shugan Heluo Xingpi Decoction shows anti-hepatic fibrosis effect, with a greater effect at higher doses. Regulating Wnt/β-Catenin signaling pathway may be one of the underlying molecular mechanisms.