In recent years, significant progress has been made in the field of liver transplantation in terms of donor expansion, technological innovation and perioperative management. Machine perfusion technology, through dynamic repair and assessment of donor liver quality, can effectively reduce postoperative complications and increase the utilization rate of marginal donor livers. The optimization of split liver transplantation technology combined with normothermic perfusion further alleviates the shortage of donors, but its promotion is still limited by technical barriers. Xenotransplantation has achieved preclinical breakthroughs in the field of genetically modified pig livers, but ethical and immune barrier issues need to be urgently resolved. In the field of liver cancer liver transplantation, the focus is on neoadjuvant treatment with immune checkpoint inhibitors and the development of recurrence prediction models, which promotes precise treatment. For perioperative management, the optimization of individualized immunosuppressive regimens, artificial liver support, and strategies for the prevention and control of vascular complications has significantly improved patients’ survival rates. Personalized treatment for children, elderly recipients, and recipients with multiple comorbidities provides new ideas for liver transplantation in special populations. In the future, liver transplantation research may focus on the integration of multidisciplinary approaches, individualized treatment and emerging technologies to advance the global liver transplantation cause to new heights.

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P＜0.01,P＜0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73％and 90.57％in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33％in the treatment group and 66.04％in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P＜0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.

Seven triterpenoids were isolated and purified from the 95% aqueous EtOH extract whole plants of P. villosa by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Based on physicochemical properties and spectral analyses, the structures of the seven compounds were identified as 29-acetoxyoleanolic acid-3-O-α-L-arabinopyranoside (1), oleanolic acid (2), 3β-hydroxy-24-norursa-4(23),12,20(30)-trien-28-oic acid (3), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid (4), ursolic acid (5), hederagenin (6), oleanolic acid 3-O-arabinoside (7). Compound 1 is a new compound. Compounds 3, 4, 6, and 7 are isolated from P. villosa for the first time. All compounds were assayed for their anti-inflammatory activity by the prodution of NO in lipopolysaccharide-stimulated RAW 264.7 cells. The results showed that compounds 1, 2, 3, 4, 6, and 7 significantly inhibited the NO release.