In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

Objective To explore the relationship between serum thioredoxin 1(Trx1),programmed cell death factor 4(PDCD4),aquaporin 4(AQP4)expression and cognitive function in patients with Parkinson's disease(PD).Methods A total of 145 PD patients(PD group)were selected as the study subjects,and patients were divided into the cognition impairment(CI)group 43 cases and the no CI group(102 cases)according to the mini-mental state examination(MMSE).Another 105 healthy subjects in the same period were taken as the control group.General patient data were collected and analyzed.The serum expression of Trx1,PDCD4 and AQP4 were detected by ELISA.The correlation between serum levels of Trx1,PDCD4 and AQP4 in PD patients and CI score were analyzed by Pearson method.Multivariate Logistic regression was used to analyze influencing factors of CI in PD patients.The predictive values of serum Trx1,PDCD4 and AQP4 levels for the occurrence of CI in PD patients were analyzed by receiver operating characteristic(ROC)curve.Results Serum levels of Trx1 and AQP4 were lower in the PD group than those of the control group,and PDCD4 was higher in the PD group than that of the control group(P＜0.05).In the CI group,PD duration and PDCD4 levels were higher than those of the no CI group(P＜0.05),and BMI,years of education,MMSE score,MoCA score,Trx1 and AQP4 were lower than those in the no CI group(P＜0.05).In the PD group,serum Trx1 and AQP4 levels were positively correlated with MMSE and MoCA scores,and serum PDCD4 levels were negatively correlated with MMSE and MoCA scores(P＜0.05).The long course of disease and increased PDCD4 levels were risk factors for CI in PD patients,while increased Trx1 and AQP4 levels were protective factors for CI in PD patients(P＜0.05).Serum Trx1,PDCD4,AQP4 levels and the combined AUC for predicting CI in PD patients were 0.820,0.741,0.831 and 0.932,respectively,and the combined prediction was better than the respective prediction alone.Conclusion Serum Trx1,AQP4 and PDCD4 are closely related to cognitive function,and the combination of the three has high predictive value for CI in PD patients.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

Objective To explore the relationship between serum thioredoxin 1(Trx1),programmed cell death factor 4(PDCD4),aquaporin 4(AQP4)expression and cognitive function in patients with Parkinson's disease(PD).Methods A total of 145 PD patients(PD group)were selected as the study subjects,and patients were divided into the cognition impairment(CI)group 43 cases and the no CI group(102 cases)according to the mini-mental state examination(MMSE).Another 105 healthy subjects in the same period were taken as the control group.General patient data were collected and analyzed.The serum expression of Trx1,PDCD4 and AQP4 were detected by ELISA.The correlation between serum levels of Trx1,PDCD4 and AQP4 in PD patients and CI score were analyzed by Pearson method.Multivariate Logistic regression was used to analyze influencing factors of CI in PD patients.The predictive values of serum Trx1,PDCD4 and AQP4 levels for the occurrence of CI in PD patients were analyzed by receiver operating characteristic(ROC)curve.Results Serum levels of Trx1 and AQP4 were lower in the PD group than those of the control group,and PDCD4 was higher in the PD group than that of the control group(P＜0.05).In the CI group,PD duration and PDCD4 levels were higher than those of the no CI group(P＜0.05),and BMI,years of education,MMSE score,MoCA score,Trx1 and AQP4 were lower than those in the no CI group(P＜0.05).In the PD group,serum Trx1 and AQP4 levels were positively correlated with MMSE and MoCA scores,and serum PDCD4 levels were negatively correlated with MMSE and MoCA scores(P＜0.05).The long course of disease and increased PDCD4 levels were risk factors for CI in PD patients,while increased Trx1 and AQP4 levels were protective factors for CI in PD patients(P＜0.05).Serum Trx1,PDCD4,AQP4 levels and the combined AUC for predicting CI in PD patients were 0.820,0.741,0.831 and 0.932,respectively,and the combined prediction was better than the respective prediction alone.Conclusion Serum Trx1,AQP4 and PDCD4 are closely related to cognitive function,and the combination of the three has high predictive value for CI in PD patients.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.
Humans ; Colorectal Neoplasms/therapy* ; Machine Learning ; Female ; Male ; Middle Aged ; Neoplasm Metastasis ; Algorithms ; Medicine, Chinese Traditional/methods* ; Aged ; Adult ; Kaplan-Meier Estimate

Objective To investigate the value of quantitative CT(QCT)parameters related to abdominal and dorsal fat content for predicting early postoperative complications of esophageal cancer.Methods A total of 184 patients who underwent radical esophageal cancer surgery were retrospectively collected and divided into complication group(n=76)and control group(n=108)according to whether early postoperation complication(within 30 days after surgery)occurred or not.QCT was used to obtain parameters related to abdominal and dorsal fat content,including visceral fat area(VFA),subcutaneous fat area(SFA),VFA/SFA and the degree of muscle fat infiltration(MFI)of posterior vertebral muscles based on L3 central-level CT images.Univariate analysis and multivariate logistic regression were used to analyze clinical and pathological data as well as QCT parameters related to abdominal and dorsal fat content to screen independent risk factors for early postoperative complications of esophageal cancer.Then receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each independent risk factor alone and their combination for predicting early postoperative complications of esophageal cancer.Results VFA/SFA and MFI degree of posterior vertebral muscles were both independent risk factors for early postoperative complications of esophageal cancer(OR=5.121,1.110,both P＜0.05).The AUC of VFA/SFA and MFI degree of posterior vertebral muscle was 0.81 and 0.77,respectively,while of their combination was 0.84.Conclusion QCT parameters related to abdominal and dorsal fat content could be used to effectively predict early complications of esophageal cancer after surgery.

Consumptive thirst is widely discussed in Huangdi Neijing and it is classified as a"strange disease"in Suwen·Strange Diseases Treatise,which reflects the intractable nature of consumptive thirst.This paper explores and analyzes consumptive thirst based on the core concept in Huangdi Neijing.First,this paper approaches the subject through the use of image thinking method from Huangdi Neijing,recognizing that consumptive thirst can lead to changes in the internal climate of the human body.Then,guided by the theories of essence and qi,yin and yang,and the five elements in Huangdi Neijing,it deconstructs and analyzes the causes of these changes and the laws of qi transformation.It points out that the changing climate of consumptive thirst is characterized by"heat symptoms".The main cause of"heat symptoms"is spleen deficiency and excessive dampness,and its qi transformation law is the heat transformation of Shaoyin.The intractable nature of consumptive thirst is mainly reflected in the uncontrolled"heat symptoms"caused by the imbalance of the five elements.Based on the understanding of the heat symptoms of consumptive thirst,this paper proposes a treatment strategy for preventing the disease by resolving dampness and regulating the spleen,harmonizing kidney qi to prevent progression,and balancing yin and yang to treat chronic and recalcitrant conditions.The aim is to provide a reference for optimizing the treatment of consumptive thirst.

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.
Humans ; Klebsiella pneumoniae ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Peritoneal Dialysis/adverse effects* ; Peritonitis/drug therapy* ; Risk Factors ; Treatment Failure ; Escherichia coli