Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Tricuspid regurgitation(TR)cases are widely distributed in China.Poor clinical drug efficacy,high surgical risk,and poor prognosis for right heart failure are found in patients with moderate or severe TR.In recent years,with the innovation of valve instruments and the development of technology,transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery.Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments.Therefore,this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Objective To investigate the correlation between the expression of Toll-like receptor 4(TLR4)and chitosanase 3-like protein 1(CHI3L1)in colon cancer tissue and the prognosis of patients after radical surgery.Methods A total of 152 patients who underwent radical colon cancer surgery in our hospital from January 2017 to May 2018 were collected and divided into the good prognosis group(n=97)and the poor prognosis group(n=47)according to the 5-year survival status after surgery.Immunohistochemical staining was applied to detect the expression levels of TLR4 and CHI3L1 in colon cancer tissues and adjacent tissues;the correlation between the expression of TLR4 and CHI3L1 in colon cancer tissue and the prognosis of patients was analyzed,and the influencing factors for prognosis of colon cancer patients were analyzed.Results The positive expression rates of TLR4 and CHI3L1 in colon cancer tissues were obviously higher than those in adjacent tissues(P<0.05).The expression of TLR4 in colon cancer tissue was related to the degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05),the expression of CHI3L1 was related to the tumor diameter,degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05).Compared with the good prognosis group,the poor prognosis group had higher proportions of patients with poorly differentiated tumor,clinical stageⅢ,lymph node metastasis,and positive expression of TLR4 and CHI3L1(P<0.05).The 5-year survival rate of patient with TLR4 positive expression was 60.38%,which was lower than that of 86.84% of patients with TLR4 negative expression(χ2=9.104,P<0.05);the 5-year survival rate of patients with CHI3L1 positive expression was 58.06%,which was lower than that of 84.31% of patients with CHI3L1 negative expression(χ2=10.935,P<0.05).The positive expression of TLR4 and CHI3L1,poorly differentiated tumor,clinical stage Ⅲ,and lymph node metastasis were the independent risk factors for the prognosis of colon cancer patients(P<0.05).Conclusion TLR4 and CHI3L1 are related to the occurrence and clinicopathological features of colon cancer,and the positive expression of TLR4 and CHI3L1 in colon cancer tissues is not conducive to the prognosis of patients,so both of them are expected to become clinical treatment targets.

Objective To develop a prediction tool for post-endoscopic retrograde cholangiopancreatography(ER-CP)early biliary tract infection(PEEBI)in patients with choledocholithiasis,and assist clinical decision-making be-fore ERCP and early personalized intervention after ERCP.Methods An observational bidirectional cohort study was adopted to select inpatients with choledocholithiasis who underwent ERCP in a hospital.Directed acyclic graph(DAGs)and the least absolute shrinkage and selection operator(LASSO)were used to predict PEEBI based on lo-gistic regression,and the models were compared and validated internally and externally.Results From January 1,2020 to September 30,2023,a total of 2 121 patients with choledocholithiasis underwent ERCP were enrolled,of whom 77(3.6％)developed PEEBI,mostly in the first 2 days after surgery(66.2％).The major influencing fac-tors for PEEBI were non-iatrogenic patient-related factors,namely diabetes mellitus(OR=2.43,95％CI:1.14-4.85),bile duct malignancy(OR=3.95,95％CI:1.74-8.31)and duodenal papillary diverticulum(OR=4.39,95％CI:1.86-9.52).Compared with the LASSO model,the DAGs model showed higher ability(3.0％)in com-prehensive discrimination(P=0.007),as well as good differentiation performance(D=0.133,P=0.894)and cal-ibration performance(x2=5.499,P=0.703)in external validation.Conclusion The DAGs model constructed in this study has good predictive performance.With the help of this tool,targeted early preventive measures in clinical practice can be taken to reduce the occurrence of PEEBI.

Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

Objective To investigate the clinical characteristics of female migraine patients with patent foramen ovale(PFO)and design a risk prediction model for PFO in female migraine patients(migraineur patients PFO risk prediction model,MPRPM).Methods Female migraine patients who visited Zhongshan Hospital,Fudan University from Jun 1,2019 to Dec 31,2022 were included.Preoperative information and follow-up results after discontinuation of medication were collected.Patients were divided into PFO-positive and PFO-negative groups based on transesophageal echocardiography results.A multivariate Logistic regression model and a random forest model were constructed,and the random forest model was validated multidimensionally.Key features were selected based on the mean decrease accuracy(MDA)to construct MPRPM.Results A total of 305 female patients were included in the study,with 204 patients in the PFO-positive group and 101 patients in the PFO-negative group.Multivariate Logistic regression analysis showed that age at migraine onset,attack frequency,severe impact on life during attacks,exercise-related headaches,menstruation-induced headaches,aura migraines,and a history of cryptogenic stroke were predictive factors for PFO positivity.The random forest model effectively predicted the incidence of PFO in female migraine patients,with an AUC of 0.895(95%CI:0.847-0.943).MPRPM demonstrated a sensitivity of 71.6%and specificity of 91.1%(AUC:0.862,95%CI:0.818-0.906,P<0.001).The optimal cut-off value was 2.5 points.Patients correctly classified by the model showed a higher rate of symptom improvement compared to incorrectly classified patients(94.3%vs.82.0%,P=0.023).Conclusion We identified predictive factors for PFO in migraine patients.MPRPM can provide guidance in the diagnostic process and therapeutic decision-making for female migraine patients,assist in patient triage,and reduce the healthcare burden.

Child ; Humans ; Acquired Immunodeficiency Syndrome/drug therapy* ; Retrospective Studies ; Anti-Retroviral Agents/therapeutic use* ; HIV Infections/epidemiology* ; China/epidemiology* ; Anti-HIV Agents/therapeutic use*

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.
Mice ; Animals ; Cathartics ; Moringa oleifera ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Constipation

Objective: To investigate the feasibility of Cai tube-assisted natural orifice specimen extraction surgery (NOSES) in gastrointestinal surgery. Methods: This was a descriptive case-series study. Inclusion criteria: (1) colorectal or gastric cancer diagnosed by preoperative pathological examination or redundant sigmoid or transverse colon detected by barium enema; (2) indications for laparoscopic surgery; (3) body mass index <30 kg/m² (transanal surgery) and 35 kg/m² (transvaginal surgery); (4) no vaginal stenosis or adhesions in female patients undergoing transvaginal specimen extraction; and (5) patients with redundant colon aged 18-70 years and a history of intractable constipation for more than 10 years. Exclusion criteria: (1) colorectal cancer with intestinal perforation or obstruction, or gastric cancer with gastric perforation, gastric hemorrhage, or pyloric obstruction; (2) simultaneous resection of lung, bone, or liver metastases ; (3) history of major abdominal surgery or intestinal adhesions; and (4) incomplete clinical data. From January 2014 to October 2022, 209 patients with gastrointestinal tumors and 25 with redundant colons who met the above criteria were treated by NOSES utilizing a Cai tube (China invention patent number:ZL201410168748.2) in the Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University. The procedures included eversion and pull-out NOSES radical resection in 14 patients with middle and low rectal cancer, NOSES radical left hemicolectomy in 171 patients with left-sided colorectal cancer, NOSES radical right hemicolectomy in 12 patients with right-sided colon cancer, NOSES systematic mesogastric resection in 12 patients with gastric cancer, and NOSES subtotal colectomy in 25 patients with redundant colons. All specimens were collected by using an in-house-made anal cannula (Cai tube) with no auxiliary incisions. The primary outcomes included 1-year recurrence-free survival (RFS) and postoperative complications. Results: Among 234 patients, 116 were male and 118 were female. The mean age was (56.6±10.9) years. NOSES was successfully completed in all patients without conversion to open surgery or procedure-related death. The negative rate of circumferential resection margin was 98.8% (169/171) with both two positive cases having left-sided colorectal cancer. Postoperative complications occurred in 37 patients (15.8%), including 11 cases (4.7%) of anastomotic leakage, 3 cases(1.3%) of anastomotic bleeding, 2 cases (0.9%) of intraperitoneal bleeding, 4 cases (1.7%) of abdominal infection, and 8 cases (3.4%) of pulmonary infection. Reoperations were required in 7 patients (3.0%), all of whom consented to creation of an ileostomy after anastomotic leakage. The total readmission rate within 30 days after surgery was 0.9% (2/234). After a follow-up of (18.3±3.6) months, the 1-year RFS was 94.7%. Five of 209 patients (2.4%) with gastrointestinal tumors had local recurrence, all of which was anastomotic recurrence. Sixteen patients (7.7%) developed distant metastases, including liver metastases(n=8), lung metastases(n=6), and bone metastases (n=2). Conclusion: NOSES assisted by Cai tube is feasible and safe in radical resection of gastrointestinal tumors and subtotal colectomy for redundant colon.
Humans ; Male ; Female ; Middle Aged ; Aged ; Anastomotic Leak/surgery* ; Stomach Neoplasms/surgery* ; Retrospective Studies ; Laparoscopy ; Rectal Neoplasms/surgery* ; Colectomy ; Postoperative Complications ; Liver Neoplasms/surgery* ; Treatment Outcome