ObjectiveTo investigate the relationship between Jiaotai pill (JTP), its main component berberine (BBR), and the serotonin (5-HT) system in regulating islet hormone secretion and alleviating pancreatic β-cell dysfunction during type 2 diabetes mellitus (T2DM) progression.MethodsT2DM rat model was established using a high-fat diet and streptozotocin injection. JTP, BBR, and Metformin were intragastrically administered for 35 days. The analyzed indices included blood glucose, blood lipids, islet hormones, and proteins related to 5-HT synthesis, secretion, and transport. Additionally, an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1 (TPH1) inhibition.ResultsJTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats. Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion. However, the administration of JTP and BBR reversed these effects. Furthermore, JTP and BBR upregulated the expression of TPH1(P = .0194, P = .0413) transglutaminase 2 (TGase2; P = .0492, P = .0349), serotonin transporter (SERT, P = .0090), and 5- hydroxytryptamine 1F receptor (5-HT1FR) in the islet 5-HT pathway (P = .0194). In the cell model, the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition (P = .001), suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.ConclusionThe islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM. JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.

Macrophages, as important immune cells, are involved in the key processes that maintain the homeostasis of intrahepatic microenvironment. Recent studies have shown that different liver diseases can induce macrophage polarization (MPP) and form M1 and M2 phenotypes with mutual antagonism. The former promotes the clearance of pathogens and inhibits tumor progression, while the latter exerts an anti-inflammatory effect and promotes tissue repair. However, there are significant differences in the mechanism of action and phenotypic switching of MPP in different liver diseases or at different pathological stages of the disease. This article focuses on the origin and polarization characteristics of intrahepatic macrophages and summarizes the research advances in the role of MPP in the pathogenesis and therapeutic drugs of non-neoplastic liver diseases such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and liver fibrosis, in order to explore the potential of MPP in regulating the immune response and inflammatory response of liver diseases.

Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.

Objective:To investigate the clinical effect of using free bilateral anterolateral thigh flaps(ALTF) in series to repair large area soft tissue defects of forearm.Methods:The clinical data of 11 patients with large soft tissue defects of forearm admitted in the Department of Plastic(Repair and Reconstruction) Surgery, Lishui Hospital of Zhejiang University from March 2014 to December 2021 were retrospectively analyzed, including 8 males and 3 females. Aged 36 to 68 years old, with an average of 48 years old. VSD treatment was performed after debridement, and until fresh removed 3 to 5 days after the operation. Until the wound was fresh. The wound was repaired with free bilateral ALTF in series until fresh. The size of the forearm wound was 18 cm×15 cm-28 cm×13 cm. The cut area of a single flap was 10 cm×8 cm-20 cm×13 cm. The series of bilateral flaps: One of the flaps was used as the proximal flap, and its vascular pedicle was anastomosed with the arteries and veins of the recipient area. The other flap was used as the distal flap, and the arteries and veins between the 2 ALTFs on both sides were anastomosed. The vascular pedicle beyond the distal flap was ligated or anastomosed to the distal end of the ulnar artery or the distal end of the radial artery. The flap and the surrounding skin of the recipient area were sutured immediately. The donor sites of the flap was closed directly. Periodic and regular outpatient follow-up was performed after operation and the clinical efficacy was analyzed.Results:All the flaps successfully survived after the surgery. The postoperative follow-up lasted for 6-18 months, 12 months in average. The flaps survived well with good soft texture, without swelling, the capillary reaction time was normal, without surface ulceration, in rosy colour and restored protective sensations. The hand function of the affected limb recovered well. The wound at donor sites healed well without complications. At the last follow-up, the hand function of the affected limb was evaluated by the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the result was 7 in excellent and 4 in good. The patients were satisfied with the flap and the therapeutic effect.Conclusion:The free bilateral ALTF in series can be used to repair a wound surface with large area, and the donor site can be closed at the same time. It is an effective method to repair large soft tissue defect of forearm.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease with a high risk of multiple organ failure, sepsis, and death. ACLF activates innate and acquired immune responses in human body and thus leads to the progression of persistent systemic inflammatory response syndrome and multiple organ dysfunction, leading to the high mortality rate of this disease. Dysregulated immune response plays a key role in disease progression, and immunotherapy may help to target immune-mediated organ damage and inhibit the progression of liver failure. This article reviews the role and mechanism of drugs and means with a potential immune regulatory effect in ACLF, in order to provide a reference for immunotherapy for ACLF.

The development and progression of nonalcoholic fatty liver disease (NAFLD) have complex potential mechanisms. The traditional “two-hit” pathophysiological theory has been challenged, and in recent years, an increasing number of studies have been performed to investigate the interaction between insulin resistance, adipokines, and other unknown pathogenic factors in various organs. This article summarizes the factors of the liver, intestinal tract, hypothalamus, and extracellular cysts, as well as genetic factors, with an emphasis on the synergistic mechanism of action of the liver and extrahepatic organs in the pathogenesis of NAFLD, in order to provide a reference for obtaining new insights into NAFLD regulatory network and determining new targets for the prevention and treatment of NAFLD.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

At present, hepatic encephalopathy has a relatively high mortality and thus greatly affects patients’ quality of life. This article describes the changes of intestinal flora in patients with hepatic encephalopathy and analyzes the mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods. It is pointed out that the development of hepatic encephalopathy is closely associated with intestinal flora, and clinical treatment by regulating intestinal flora has achieved a marked effect in patients with hepatic encephalopathy. In the future, the research on intestinal flora in patients with hepatic encephalopathy can be deepened to provide better regimens for the treatment of hepatic encephalopathy.

As a novel form of programmed cell death different from cell necrosis, apoptosis, and autophagy discovered in recent years, pyroptosis is characterized by cell membrane rupture and release of cell contents and proinflammatory factors mediated by gasdermin, thus leading to cell death. Pyroptosis signaling pathways can be classified into classical pathways dependent on caspase-1 and non-classical pathways dependent on caspase-4/5/11; the activation of caspase-1 in classical pathways depends on the function of inflammasome, while the direct activation of caspase-4/5/11 is observed in non-classical pathways, which leads to the lysis of gasdermin D and induce the formation of membrane pores, the maturation and release of interleukin-1β and interleukin-18, and the rupture of cell membrane to cause pyroptosis. Latest research has shown that pyroptosis plays an important role in the development and progression of chronic liver diseases. This article introduces the mechanism of pyroptosis and summarizes the role of pyroptosis in the development and progression of nonalcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma, in order to provide new ideas and methods for the prevention and treatment of liver diseases in clinical practice.

Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.