This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

OBJECTIVE: To explore the differences in clinical efficacy between enhanced workflows and express workflows in robotic-assisted total hip arthroplasty(THA). METHODS: A retrospective analysis was conducted on 46 patients who underwent robotic-assisted THA between November 2020 and May 2021. They were divided into the enhanced workflows group and the express workflows group based on the surgical methods. There were 20 patients in the enhanced workflows group, including 11 males and 9 females;aged from 51 to 78 years old with an average of (67.30±7.52) years old. The BMI ranged from 18.24 to 24.03 kg·m^-2 with an average of(23.80±3.01) kg·m^-2. There were 26 patients in the express workflows group, including 12 males and 14 females;aged from 57 to 84 years old with a mean age of (67.58±7.29) years old, and their BMI ranged from 19.72 to 30.08 kg·m^-2 with an average of (24.41 ±2.92) kg·m^-2. The operation time, hospital stay, and perioperative complications of the patients were recorded. The postoperative acetabular prosthesis anteversion angle, abduction angle, limb length, and offset distance data were measured. The Harris hip score at the latest follow-up was recorded. RESULTS: All patients completed the surgery as planned and were followed up, with the follow-up period ranging from 47 to 54 months with a mean of (49.78±1.85) months and the length of hospital stay ranging from 2 to 11 days with an average of (6.57±1.82 ) days. The operation time of enhanced workflows group was (93.41±16.41) minutes, which was longer than that of the express workflow groups (75.19±18.36) minutes, and the difference was statistically significant (P<0.05). In enhanced workflows group, the postoperative acetabular anteversion angle was (19.20±4.46)°, the limb length discrepancy was (-1.55±9.13) mm, and changes of the offset was (-5.15±6.77) mm. The corresponding values in express workflows group were (20.46±3.29)°, (2.19±4.39) mm, and (-2.39±4.34) mm, respectively. There was no statistically significant difference in these indicators between the two groups(P>0.05). One patient in the enhanced workflows group developed deep venous thrombosis after surgery. No cases of dislocation or periprosthetic infection. At the latest follow-up, all patients had well-positioned prostheses without loosening. Harris hip score was (90.50±1.67) points in enhanced workflows group and (90.73±2.36) points in the express workflows group, with no statistically significant difference between the two groups (P>0.05). CONCLUSION The clinical efficacy of robot assisted total hip arthroplasty technology is satisfactory. The enhanced workflows will increase the surgical time. For patients with normal anatomical hip joint disease, this study did not find significant advantages in joint stability and functional scoring for the enhanced workflows.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Male ; Female ; Aged ; Middle Aged ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Aged, 80 and over ; Workflow ; Treatment Outcome

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Objective To construct machine learning models that can be used to predict AUC fold change(FC)using a database of existing pharmacokinetic(PK)and drug-drug interaction(DDI)information,which can be used to explore the possibility of predicting existing drug interactions and to provide certain rational recommendations for clinical drug use.Methods PK data of DDIs and AUC fold change data were extracted from FDA-approved drug labels.Peptide and pharmacodynamic(PD)information related to drug interactions were retrieved through DrugBank,and PPDT identification of relevant peptide IDs was performed using Protein Resource(UniProt),and a matrix normalization code was used to generate multidimensional vector data that were easy to analysis.The effect of PPDT on the AUC,and the resulting multiplicity change was used as the dependent variable for machine learning model construction.The model with the smallest root mean square error(RMES)value was used for model construction to train a bagged decision tree(Bagged)prediction model.The models were tested using the trained models for some of the drug tests.The models were evaluated by reviewing the available literature findings on detection of drug interaction pairs and analyzing and comparing the predicted values.Results A total of 16 pairs of model drug pairs were tested for the effects of 16 drugs on tacrolimus,and it was found that the accuracy of the prediction of the presence or absence of drug interactions was 81.25％;the prediction results were classified according to the FDA standard classification of the strong and weak for the strength of drug interactions,and the results showed that the prediction of the strength of drug interactions,with a large deviation from the larger prediction was less.Conclusion The evaluation of the model to predict the presence or absence of drug interactions was general;however,after classifying the strengths and weaknesses of drug interactions,the prediction of drug interactions was better,and the prediction results indicated that the model prediction performance has a certain reference value for potential DDI assessment before clinical trials.

Objective:To analyze awareness, willingness, the status of using, and related factors of HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in Shaanxi Province to provide a reference for the next step of HIV prevention and control strategy.Methods:Using a cross-sectional study design from March to May 2022, with the assistance of MSM social organizations in Xi'an, relying on the network platform and MSM Social organizations, a convenient sampling method was used to recruit MSM with an estimated sample size of 900. The inclusion criteria were male aged ≥18, having had same-sex sexual intercourse in the last twelve months, HIV-negative or unknown status of infection. An electronic questionnaire was made with the help of questionnaire-star and an anonymous self-administered questionnaire was used to collect information on socio-demographic characteristics, sexual behavior, awareness and using of PrEP, etc. A logistic regression model was used to analyze related factors of PrEP awareness and use in MSM. SPSS 25.0 software was used for statistical analysis. Results:Among 981 MSM subjects, 76.55% (751/981) had heard of PrEP, and 42.51% (417/981) were aware of PrEP. Among those who knew about PrEP, 74.34% (310/417) had homosexual sexual activity in the last six months, 99.03% (307/310) were willing to use PrEP, and 40.97% (127/310) were using PrEP. The multivariate logistic regression analysis model results showed that nationality (other ethnic groups:a OR=4.48,95% CI:1.28-15.68),education level (high school or technical secondary school: a OR=3.01,95% CI:1.49-6.07; universities or colleges: a OR=2.86,95% CI:1.47-5.57; master degree: a OR=5.10,95% CI:2.37-10.98), monthly income 5 000-10 000 yuan (a OR=1.70,95% CI: 1.00-2.88), tested for HIV in the past 12 months (a OR=1.87,95% CI:1.34-2.61) were related factors of PrEP knowledge awareness. Singlehood (a OR=0.46,95% CI:0.26-0.81) and consulted professionals about PrEP (a OR=9.56,95% CI:4.58-19.96) were related factors of PrEP use. Conclusions:The proportion of willingness to use PrEP was higher among MSM in Shaanxi Province, but the awareness rate and utilization rate of MSM for PrEP were low. The cognition of PrEP should be further improved to promote the correct use of PrEP among MSM.

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.