ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

BACKGROUND: Neoadjuvant immunochemotherapy has emerged as an indispensable therapeutic modality for non-small cell lung cancer (NSCLC). However, its clinical application experience remains limited, and the associations between various clinical factors and treatment benefits remain undefined. This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with stage IB-IIIB NSCLC in a real-world setting, analyze survival outcomes among subgroups with diverse clinical characteristics, and identify potential clinical predictive factors for pathological response. METHODS: This study included patients with stage IB-IIIB NSCLC who underwent radical lung resection after 2-4 cycles of neoadjuvant immunochemotherapy at Peking University People's Hospital between August 2019 and March 2024. Medical records and follow-up information were collected to analyze therapeutic response, adverse events and survival outcomes. Logistic analysis was used to identify clinical predictors of pathological response. RESULTS: Among 183 enrolled patients, 116 (63.4%) were stage III. Grade 3-4 immune-related adverse events (irAEs) occurred in 39 (21.3%) patients. Radiographic complete response (CR) or partial response (PR) was achieved in 118 (64.5%) patients. R0 resection was achieved in 180 (98.4%) patients. Major pathologic response (MPR) was observed in 107 (58.5%) patients, with 78 (42.6%) achieving pathologic complete response (pCR). Squamous cell carcinoma and radiographic objective response were associated with pathological response (pCR/MPR). With a median follow-up of 22.1 [interquartile range (IQR): 18.3-32.2] months, the 2-year event-free survival (EFS) and overall survival (OS) rates were 82.5% and 90.4%, respectively. Achievement of pathological response (pCR/MPR) was correlated with prolonged survival outcomes. CONCLUSIONS Neoadjuvant immunochemotherapy is safe and effective for patients with stage IB-IIIB NSCLC. Patients achieving pCR or MPR exhibit significantly better survival benefits from neoadjuvant immunochemotherapy. Squamous cell carcinoma and radiographic objective response can serve as clinical predictors of pathological response.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Lung Neoplasms/mortality* ; Female ; Middle Aged ; Neoadjuvant Therapy/adverse effects* ; Aged ; Neoplasm Staging ; Adult ; Immunotherapy/adverse effects* ; Treatment Outcome ; Retrospective Studies

[This corrects the article DOI: 10.1016/j.apsb.2021.08.008.].

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

Public health and social measures (PHSMs) are one of the most important measures in the prevention and control of COVID-19 and have also been effective in suppressing the spread of influenza viruses, but their effectiveness has not been fully investigated. This study aimed to review the progress of research on the impact of PHSMs on influenza during the COVID-19 pandemic based on the latest evidence of the effectiveness of various PHSMs in controlling transmission of influenza viruses, to provide scientific evidence for optimizing influenza prevention and control strategies.

Public health and social measures (PHSMs) are one of the most important measures in the prevention and control of COVID-19 and have also been effective in suppressing the spread of influenza viruses, but their effectiveness has not been fully investigated. This study aimed to review the progress of research on the impact of PHSMs on influenza during the COVID-19 pandemic based on the latest evidence of the effectiveness of various PHSMs in controlling transmission of influenza viruses, to provide scientific evidence for optimizing influenza prevention and control strategies.

Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.

Objective:To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus.Methods:The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m 2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m 2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m 2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results:SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5–7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion:SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.

Objective:To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus.Methods:The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m 2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m 2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m 2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results:SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5–7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion:SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.