Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P＜0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P＞0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.

In order to preliminarily evaluate the efficacy and safety of endoscopic intermuscular dissection (EID) for the treatment of rectal neuroendocrine tumors (R-NETs), a retrospective observational study was conducted on 8 consecutive patients with R-NETs confirmed by postoperative pathology at South China Hospital, Medical School, Shenzhen University from January 2022 to October 2023. The therapeutic efficacy, incidence of complications, and follow-up results were mainly analyzed. The results showed that all 8 cases achieved complete resection after EID, with operation times ranging from 40 to 90 minutes. No bleeding, perforation, fever or electrocoagulation syndrome occurred after operation. The hospital stay was 4 to 6 days. During follow-up of 3 to 24 months, there was no local recurrence or metastasis. Therefore, a preliminary conclusion can be drawn that EID is a safe and feasible treatment for R-NETs.

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/chemistry* ; Research ; Drug Discovery ; China

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

AIM:To evaluate the correlation between axial lengths and anterior segment parameters using swept-source optical coherence tomography(SS-OCT).METHODS:For the cross-sectional clinical study, a total of 109 adult volunteers with different degrees of myopia recruited from January 1, 2022, to March 31, 2022, at the ophthalmology clinic of the First Affiliated Hospital of Zhengzhou University were included. Participants were divided into 4 groups based on axial length(AL): group A(AL≤24.0mm), group B(24.0mm26.0mm). Anterior segment examinations were performed using SS-OCT, including: central corneal thickness(CCT), lens thickness(LT), anterior chamber depth(ACD), anterior chamber width(ACW), angle opening distance(AOD500), angle recess area(ARA500), trabecular iris space area(TISA500), trabecular iris angle(TIA500), crystalline lens rise(CLR). The relationships between these data and AL, spherical equivalent(SE)were analyzed.RESULTS:There was no difference in the comparison of CCT among the four groups(P>0.05). There were differences in SE, LT, ACD, ACW, AOD500, ARA500, TISA500, TIA500 and CLR among the four groups(all P<0.01). SE and LT were negatively correlated with AL(r=-0.75, -0.41, all P<0.01); ACD, ACW and CLR were positively correlated with AL(r=0.58, 0.45, 0.54, all P<0.01); AOD500, ARA500, TISA500 and TIA500(temporal and nasal side)were positively correlated with AL(all P<0.01). ACD and CLR were negatively correlated with SE(r=-0.21,-0.25, all P<0.01), and LT was positively correlated with SE(r=0.21, P<0.05).CONCLUSION:As AL increases, CCT remains unchanged while the ACD and ACW increase. The position of the crystalline lens moves backward and LT decreases.

Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Neoplasms

Mining data from traditional Chinese medicine(TCM) prescriptions is one of the important methods for inheriting the experience of famous doctors and developing new drugs. However, current research work has problems such as to be optimized research plans and non-standard statistics. The main problems and corresponding solutions summarized by the research mainly include four aspects.(1)The research plan design needs to consider the efficacy and quality of individual cases.(2)The significance of the difference in confidence order of association rules needs to be further considered, and the lift should not be ignored.(3)The clustering analysis steps are complex. The selection of clustering variables should comprehensively consider factors such as the frequency of TCM, network topology parameters, and practical application significance. The selection of distance calculation and clustering methods should be improved based on the characteristics of TCM clinical data. Jaccard distance and its improvement plan should be given attention in the future. A single, unexplained clustering result should not be presented, but the final clustering plan should be selected based on a comprehensive consideration of TCM clinical characteristics and objective evaluation indicators for clustering.(4)When calculating correlation coefficients, algorithms that are only suitable for continuous variables should not be applied to binary variables. This article explained the connotations of the above problems based on the characteristics of TCM clinical research and statistical principles and proposed corresponding suggestions to provide important references for future data mining research work.
Humans ; Medicine, Chinese Traditional ; Prescriptions ; Data Mining ; Cluster Analysis ; Physicians ; Drugs, Chinese Herbal/therapeutic use*

Humans ; Ossification, Heterotopic ; Skin Diseases, Genetic ; Bone Diseases, Metabolic

Objective: To examine the safety and effectiveness of laparoscopic individualized surgical treatment for chronic traumatic diaphragmatic hernia (CTDH). Methods: The clinical data and follow-up data of 29 CTDH cases admitted to the Qilu Hospital of Shandong University or the First Affiliated Hospital of Shandong First Medical University from June 2015 to January 2023 were retrospectively analyzed. There were 21 males and 8 females, aged (49.4±17.8) years (range: 19 to 79 years). The main clinical manifestations were symptoms of the digestive system and respiratory system, and only 4 cases were asymptomatic. All patients received laparoscopic treatment (conversion to open surgery was not excluded). Intraoperative exploration (location of the hernia, contents of the hernia, diameter of the hernia ring), surgical conditions (surgical repair plan, operation time, blood loss, postoperative complications) and postoperative follow-up were analyzed and discussed. Results: Laparoscopic repair was successfully completed in 27 cases, including simple suture in 6 cases, suture and patch repair in 17 cases, the anterior abdominal wall muscle flap reversal suture and patch repair of in 3 cases, and patch bridge repair in 1 case. The operation time was (112.8±44.7) minutes (range: 60 to 200 minutes). The amount of bleeding (M(IQR)) was 35 (58) ml (range: 10 to 300 ml). The other 2 patients were converted to laparotomy. Except for one patient with transverse colon strangulation necrosis who died of aggravated pulmonary infection after surgery, the remaining 28 patients were discharged successfully. The follow-up time was 36 (24) months (range: 1 to 60 months). During the follow-up period, only two patients had occasional left upper abdominal discomfort. Twenty-seven patients with left diaphragmatic hernia had no recurrence, and the symptoms of 1 patient with right diaphragmatic hernia were relieved. Conclusion: Customized laparoscopic surgical repair for CTDH according to the location and size of the diaphragmatic defect can achieve good surgical results.
Male ; Female ; Humans ; Hernia, Diaphragmatic, Traumatic/surgery* ; Retrospective Studies ; Laparoscopy/methods* ; Postoperative Complications ; Laparotomy ; Surgical Mesh