Cognitive impairment refers to the abnormality of the hippocampus， cortex and other parts of the brain， which is manifested by the decline of cognitive abilities such as learning， memory and attention. With the increase in people's work pressure and bad living habits， the incidence of cognitive impairment is getting higher and higher， which seriously affects people's normal life. However， there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore， the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine （TCM） has the characteristics of "multi-component， multi-pathway and multi-target"， and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress， inflammation， apoptosis， autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt） signal pathway plays an important role in the transmission of intracellular and intracellular signals， and in the regulation of cellular inflammation， apoptosis， autophagy， etc. TCM monomers， TCM extracts， and TCM compounds exert anti-inflammatory， antioxidant， anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway， and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress， inflammation， apoptosis and autophagy of neurons. Finally， the recent research status of the regulation of this signaling pathway by TCM extracts， TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.

ObjectiveTo establish a managing mode for illegal and irregular acts of occupational medical examination (OME) institutions to the requirements of the new situation. Methods The OME institutions from the “Guangdong Province Key Occupational Disease Monitoring and Management Platform” were selected as the study subjects using the judgment sampling method. The clues of suspected illegal and irregular acts of OME institutions were found and submitted to the local health commission for investigation and managed according to the case information monitoring and on-site quality assessment. The OME institutions found to have illegal and irregular acts were filed and investigated according to the national law after investigation and verification. A “follow-up inspection” was conducted on five OME institutions for closed loop management. Results A total of 12 OME institutions were found to have suspected illegal and irregular acts, including seven institutions that did not meet the filing requirements for effective personnel, five institutions that conducted projects beyond the scope without filing to the provincial health authorities within 15 work days from the start of the project, and two institutions that failed to fulfill the obligation of informing and reporting to the health authorities, employers, and workers as required. After submitting relevant clues and evidence to the local health commission for investigation and management, seven institutions were not given penalty, and five institutions were given administrative penalties including two institutions were fined and warned, and three institutions were warned. No illegal or irregular acts were found in the five institutions inspected during the “follow-up inspection”. Conclusion It is beneficial to explore the managing mode of “clue discovery, clue submission, investigation and disposal, follow-up inspection” for OME institutions suspected of illegal and irregular acts, which helps urge OME institutions to work in accordance with laws and regulations and effectively protect the legitimate rights and interests of workers' occupational health.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

Objective To analyze the problems found in the on-site quality assessment of occupational medical examination (OME) institutions in Guangdong Province. Methods A total of 150 OME institutions were selected as the research subjects from Guangdong Province in 2023 using a random number table method. The on-site quality assessment was conducted by listening to reports, meeting discussion, on-site inspection, data review and human-machine assessment. The relevant assessment results were analyzed. Results Occupational disease prevention and treatment institutes (institutes, centers) and disease control and prevention centers (hereinafter referred to as "occupational prevention institutions"), public hospitals, and private institutions accounted for 8.7%, 51.3%, and 40.0% respectively. The top three categories of registered inspections were physical factors, chemical factors and dust, accounted for 98.0%, 96.7% and 96.0%, respectively, among the 150 OME institutions. A total of 1 063 rectification items were identified, and the average number of rectification items identified per occupational prevention institutions, public hospitals and private institutions was four, six and nine, respectively. The rectification rates of the four modules of quality assessment from high to low were OME work quality control, quality management system, organizational structure, and OME information reporting, accounted for 53.2%, 23.3%, 13.7% and 9.7%, respectively. The coincidence rate from high to low of occupational reporting of noise-exposure, dust-exposure, and other hazard-exposure was 92.5%, 91.1%, and 93.4%, respectively. The on-site failure rate of quality control director, technical director, chief physician, pneumoconiosis film reader, audiometry reader and pulmonary function examination operator accounted for 15.3%, 12.7%, 8.0%, 6.7%, 6.0% and 2.7%, respectively. Institutions capable of conducting registered and partially registered OME accounted for 90.7% and 6.0%, respectively. The five institutions that were unable to conduct registered OME were private institutions. A total of five private institutions were found to be suspected of illegal and irregular activities. Conclusion The problems of OME in the on-site quality assessment of OME institutions in Guangdong Province were mainly quality control. Private institutions had more prominent problems in various aspects. It is necessary to strengthen the training of key personnel such as technical directors, quality control directors, and chief physicians.

Objective:To investigate the clinical features, diagnostic methods, treatment modalities, and prognosis of parathyroid multiglandular disease (PTMGD) in primary hyperparathyroidism (PHPT) .Methods:The clinical data of 29 patients with PTMGD who underwent surgery at the General Surgery Department of the Tianjin Medical University General Hospital from Dec. 2015 to Jul. 2023 were retrospectively analyzed, including the patients' preoperative and postoperative blood calcium and parathyroid hormone, the main clinical manifestations, the involvement of other systems, the main types of pathology, the accuracy of the various examinations, and the postoperative prognosis, etc., and were compared with the 291 patients who had undergone surgery for single-glandular lesion patients were compared. SPSS25 was used to analyze the data.Results:The age of onset of PTMGD was 52.7±1.9 years compared to 56.6±0.7 years in patients with monoglandular disease, P=0.047. Tumor diameter of PTMGD was (2.05±0.1) cm and (2.34±0.6) cm of monoglandular disease, P=0.006. The preoperative blood calcium was (2.56±0.59) mmol/L in PTMGD and (2.70±0.58) mmol/L in monoglandular disease, P=0.045. Preoperative parathyroid hormone (PTH), blood calcium, and Win values were positively correlated with maximum tumor diameter in patients with PTMGD (R-values of 0.362, 0.223, and 0.352, respectively) .Neck ultrasound, neck-enhanced CT and parathyroid nuclear imaging were used to localize and diagnose the diseased parathyroid glands in this group of cases.The accuracy rates were (14/25) 56%, (10/19) 53% and (11/24) 46% in patients with PTMGD, while in patients with monoglandular disease, the accuracy rates were (233/250) 89%, (131/152) 96% and (223/232) 86%. PTMGD accuracy rate was less than that of monoglandular disease,and was statistically significant ( P-value was less than 0.001 in all cases) .The accuracy of the combined localization diagnosis of the three tests in patients with PTMGD was then improved to (13/18) 72%. The pathology of PTMGD was predominantly parathyroid hyperplasia, 45/72 (63%), compared to that of monoadenopathy 18/291 (6%), P<0.001. Parathyroid adenomas predominated in patients with monoadenopathy compared to that of PTMGD, 237/291 (82%) vs. 24/72 (33%), and the proportion of parathyroid adenomas in patients with monoadenopathy was higher than that in patients with PTMGD, P<0.001. 23 patients with PTMGD were followed up, of whom 9 showed mild elevation of parathyroid hormone postoperatively, and 1 patient showed signs of hypoparathyroidism. Conclusion:The low age of onset of multiglandular lesions in primary hyperparathyroidism, mild biochemical tests, and the difficulty of accurately locating all lesions preoperatively warrant adequate preoperative evaluation to promptly identify patients with familial multiple endocrine adenomas, as well as intraoperative bilateral parathyroid exploration in patients with suspected multiglandular lesions.

Objective To study the requirement of exogenous phosphorus for 2-year-old and 3-year-old ginseng seedings.Methods Two-and three-year-old ginsengs were used as experimental materials.Calcium superphosphate and phosphorus-free Hoagland solution were used as fertilizer,and the concentrations of P2O5 were set to be 0 mmol·L-1,0.5 mmol·L-1,1.5 mmol·L-1,3 mmol·L-1,6 mmol·L-1,8 mmol·L-1,respectively.The effects of different concentrations of phosphorus fertilizer on agronomic indexes,photosynthetic characteristics and accumulation of ginsenosides Rg1,Rb1 and Re were studied.Results The plant height,stem diameter,root weight,leaf area,relative content of chlorophyll,net photosynthetic rate and total saponins content of different year-old panax ginseng were significantly increased by applying phosphorus at 1.5-3.0 mmol·L-1.Among them,compared with the phosphorus-free group,the root weight of second-year ginseng was increased by 16％and the saponin content was increased by 24％;the root weight of third-year ginseng was increased by 89％and the saponin content was increased by 132％.The appropriate application rate of phosphorus fertilizer(phosphorus pentoxide)during the growth of second and third year ginseng was 26.6 mg and 53.3 mg of plant,respectively.Conclusion External application of suitable concentration of phosphorus fertilizer can enhance the external morphological characteristics of ginseng,improve photosynthetic physiological properties and increase the content of active ingredients.

The neural circuit is the material carrier for the realization of brain function,consisting of a complex network of different neurons.Neural circuit identification technology tracks the structure and activity of specific neural circuits,to study their adequacy and necessity for brain function,which is crucial for understanding the pathogenesis of brain diseases.As a high-tech tool in the fields of neuroscience and brain science,neural circuit identification technology has been gradually introduced into basic traditional Chinese medicine(TCM)research in recent years.This systematic review considers the principles of neural circuit identification technology and progress in its application in the field of TCM neuroscience.We note that future developments in this field should be based on the overall concept of TCM characteristics and the design of syndrome differentiation and treatment.Further research on the neural circuit mechanisms of diverse method of TCM in diseases will help to promote the deep integration of TCM and modern neuroscience.

Chemogenetic technology is a receptor-ligand system that regulates cell viability and function by changing receptor specificity and affinity, and it achieves precise neuronal regulation by specifically regulating neurons and neural circuits. At present, this technique is widely used in the study of neural circuits. This article briefly describes the application and progress of chemogenetic technology in the study of depression neural circuits, reviews the application of chemogenetic technology in several brain regions closely related to depression, such as ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and lateral habenula, and discusses the potential and challenges of chemogenetic technology as a technology for precise regulation of neural activity in future research, in order to provide reliable ideas and directions for chemogenetic technology in the study of depression neural circuits.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs,including many substrates of P-glycoprotein(P-gp).Levetiracetam,a kind of antiepileptic drugs,is a substrate of P-gp.Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. Methods:Wistar rats were divided into a low-altitude control group,a high-altitude group,a solvent group,and a P-gp induction group.After 24 h of exposure at altitude of 4 010 m,rats in the high-altitude group were given levetiracetam orally or intravenously.The plasma was respectively collected at 0.083,0.25,0.5,0.83,1.25,2,4,6,8,10,12,and 24 h after oral administration of the drug,while both plasma and brain were respectively collected at 5,45,60,120 and 240 min after intravenous injection.After 3 days administration of dexamethasone,plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam.Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The expression of P-gp in blood-brain barrier was detected by Western blotting. Results:Compared with the low-altitude control group,the area under the curve(AUC)and mean residence time(MRT)of levetiracetam were respectively decreased by 14.69%(P<0.01)and 15.42%(P<0.01),while the clearance(CL)was increased by 16.67%(P<0.01)in the high-altitude group.The ratio of brain/blood plasma drug concentration was decreased by 22.82%(P<0.05),12.42%(P<0.05),17.40%(P<0.01),and 13.22%(P<0.01)at 5,45,120,and 240 min after injection,respectively.The expression of P-gp on the blood-brain barrier was increased by 86.3%(P<0.05).Compared with the solvent control group,the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3%(P<0.05),the ratio of brain/blood plasma drug concentration was decreased by 19.3%(P<0.05). Conclusion:After acute plateau hypoxia exposure,the pharmacokinetic of levetiracetam in rats are altered,and the cerebral-blood distribution of the drug in rats is decreased,which may be related to the up-regulation of P-gp expression on the blood-brain barrier.