ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

The ocular fundus vasculature, serving as a critical window for monitoring disease progression, represents one of the primary targets of hypoxic injury. A growing body of evidence suggests associations between specific ocular vascular pathologies and sleep-disordered breathing. Obstructive sleep apnea(OSA)has been implicated in fundus lesions through its detrimental effects on the central retinal artery, retinal veins, retinal microvasculature, and choroidal vessels. Mechanistically, these effects are linked to OSA-induced intermittent hypoxia, which drives hemodynamic disturbances, oxidative stress, inflammatory responses, altered blood composition, endothelial dysfunction, and neuroendocrine/metabolic dysregulation. This review synthesizes current evidence on OSA-related retinal vascular injury and elucidates its mechanistic pathways. The goal is to identify sensitive and specific retinal vascular biomarkers to facilitate the early detection of OSA and its associated complications.

OBJECTIVE: To observe the effects of electroacupuncture (EA) with different frequencies on spermatogenic function, testicular morphology and oxidative stress in oligoasthenospermia (OAT) rats, and to explore the mechanism and the optimal parameters of EA for OAT. METHODS: Sixty SPF-grade male SD rats were randomly divided into a solvent control group, a model group, a 2 Hz EA group, a 100 Hz EA group and a 2 Hz/100 Hz EA group, with 12 rats in each group. Except for the solvent control group, the other 4 groups were administered ornidazole suspension (800 mg·kg^-1·d^-1) by gavage for 28 d to establish the OAT model. Starting from the 1st of modeling, EA was applied at "Guanyuan" (CV4), "Qihai" (CV6) and bilateral "Sanyinjiao" (SP6) and "Zusanli" (ST36) in the 3 EA groups, continuous wave of 2 Hz, continuous wave of 100 Hz, and disperse-dense wave of 2 Hz/100 Hz were used in the 2 Hz EA group, the 100 Hz EA group, and the 2 Hz/100 Hz EA group, respectively, with current intensity of 1-3 mA, 30 min a time, once every other day, for 28 consecutive days. After intervention, the testicular index was calculated, epididymal sperm quality was assessed, and the fertility ability was observed; morphology of testicular tissue was observed by HE staining, and the Johnson score was calculated; the positive expression of reactive oxygen species (ROS) in testicular tissue was detected by immunofluorescence; the activity of superoxide dismutase (SOD) and catalase (CAT), as well as the level of malondialdehyde (MDA) in testicular tissue were measured by ELISA; the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in testicular tissue was detected by Western blot. RESULTS: Compared with the solvent control group, in the model group, the testicular index, sperm concentration, sperm motility and the number of offspring were decreased (P<0.01), the seminiferous tubules atrophied and the Johnson score decreased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were decreased (P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were increased (P<0.01). Compared with the model group, in the 2 Hz EA group, the 100 Hz EA group and the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility and the number of offspring were increased (P<0.05, P<0.01), the pathological morphology of testicular tissue improved and the Johnson scores increased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were increased (P<0.05, P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were decreased (P<0.05, P<0.01). Compared with the 2 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility, as well as the CAT activity and HO-1 protein expression in testicular tissue were increased (P<0.01, P<0.05); the positive expression of ROS was decreased (P<0.01). Compared with the 100 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index was increased (P<0.01), the positive expression of ROS in testicular tissue was decreased (P<0.01). CONCLUSION EA with 2 Hz continuous wave, 100 Hz continuous wave, and 2 Hz/100 Hz disperse-dense wave can all improve the spermatogenic arrest and reduce the level of oxidative stress in testicular tissue in OAT rats, the mechanism may be related to up-regulating the protein expression of Nrf2 and HO-1 and improving oxidative stress. EA with disperse-dense wave of 2 Hz/100 Hz shows the optimal effect.
Male ; Animals ; Electroacupuncture ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; Oligospermia/genetics* ; Humans ; Testis/metabolism* ; Superoxide Dismutase/metabolism* ; Asthenozoospermia/genetics* ; Acupuncture Points ; Malondialdehyde/metabolism*

The paper introduces 5 books written by WANG Mengying, including Suixiju Chongding Huoluan Lun, Guiyan Lu, Wenre Jingwei, Wang Mengying Yi'an and Suixiju Yinshipu; and analyzes the ideas of diagnosis and treatment of cholera and the academic thoughts in treatment with acupuncture-moxibustion therapy. In pathogenesis, cholera is classified into cold and heat types. Cholera of heat type roots on qi and blood. If the pathogenic factors are mild and located shallowly, the sneezing method, followed by scraping method, is adopted to open meridians and collaterals, as well as the qi level, so as to eliminate pathogens. When the pathogens go deeply, the bloodletting technique is used to clean the toxic heat in blood level and reduce the reversed qi. For cholera of cold type, warm ironing moxibustion is delivered to promote qi circulation and disperse cold, and improve qi movement. If spasm and syncope occur in cholera, no matter of cold or heat identification, the emergent measure is operated with the external application of pungent, warm and salty herbal plaster at Yongquan (KI1). When the pathogens are almost eliminated, the herbal medicines are combined to treat the symptoms and remove the causative factors of the disease.
Acupuncture Therapy/history* ; Moxibustion/history* ; Humans ; Cholera/history* ; China ; History, Ancient ; Medicine in Literature ; Books/history*

Objective To exploring the effect of inflammatory indicators on the outcome of assisted conception of in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)in patients with ovarian endometriosis(OEM).Methods The study subjects were selected as the patients with OEM who received IVF/ICSI treatment at the Third Affiliated Hospital of Zhengzhou University from January 2019 to February 2024.Based on whether previous surgery for uterine endometriosis cyst removal had been performed,they were divided into non-surgery group(n=73)and surgery group(n=112).To explore the differences in inflammatory markers between two groups and to determine whether they have an impact on the outcome of assisted reproduction.Results The lymphocytes(L)and blastocyst formation rates of patients in surgery group were significantly higher than those in non-surgery group,platelet to lymphocyte ratio(PLR)and carbohydrate antigen 125(CA125)were significantly lower than those in non-surgery group(P＜0.05).There were no statistically significant differences in the clinical pregnancy rate and live birth rate between two groups of patients(P＞0.05).After adjusting for confounding factors,the results of multivariate Logistic regression analysis showed that L,PLR,and CA125 had no statistically significant impact on the clinical pregnancy rate and live birth rate(P＞0.05).Both maternal age and the number of embryos transferred exerted a certain influence on clinical pregnancy rates and live birth rates(P＜0.05),furthermore,the type of embryo transferred had a significant effect on clinical pregnancy rates(P＜0.05).Conclusion Compared with non-surgery group,surgery group had higher L level and lower PRL and CA125 levels,but these changes did not significantly affect clinical pregnancy or live birth outcomes in OEM patients undergoing IVF/ICSI assisted reproduction.

Objective:To develop a validation method for microbial targeted next generation sequencing (tNGS) detection for respiratorypathogens, and to evaluate the performance of the pathogen-targeted high-throughput sequencing test implemented in local hospital.Methods:Cross-sectional study. A total of 14 patients with severe pulmonary infections were admitted to Huangshi Central Hospital from December 2023 to January 2024. Samples were collected as follows:Bronchoalveolar lavage fluid (BALF) samples ( n=7) subjected to culture, fluorescent PCR, and tNGS testing. Sputum samples ( n=2) analyzed via sputum culture, fluorescent PCR, and tNGS. Throat swab samples ( n=5) tested using fluorescent PCR-capillary electrophoresis and tNGS. Reference samples were prepared using representative species such as Influenza A virus, Adenovirus C, Klebsiella pneumoniae, Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans. Jurkat cells at different concentrations were used as a source of human cells. Traditional detection methods such as fluorescent PCR-capillary electrophoresis and culture methods were used as reference methods. The detection performance of tNGS was evaluated by assessing the detection limit, precision, human cell impact, stability, cross-reactivity, and accuracy of metagenomic next-generation sequencing for pathogen detection. Results:The detection limits for Klebsiella pneumoniae, Human Adenovirus C, and Influenza A virus were 2×10 2 copies/ml, and for Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans, the detection limits were 4×10 2 copies/ml. The consistency rate of repeated detection results for all pathogens in the reference samples was 100%. The impact assessment experiment of human cells showed that when the concentration of Jurkat cells reached 1×10 6 cells/ml, Influenza A virus, Adenovirus C, Klebsiella pneumoniae, and Aspergillus fumigatus could all be detected. Stability experiments showed that there was no significant change in the number of pathogen sequences after the specimens were stored at 4 ℃ and -20 ℃ for 1 day, 4 days, and 7 days, respectively. Cross-reactivity experiments showed that when the concentration ratios of Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans were (5∶1∶1∶5), (1∶5∶5∶1), and (1∶1∶1∶1), respectively, the detection rate of closely related microbial species was 3/3. Accuracy assessment showed that the accuracy of 19 clinical specimens was 18/19 cases. Conclusion:Compared with traditional detection methods as the reference, tNGS demonstrates high sensitivity and a high positive concordance rate, underscoring its significant clinical value in the detection of respiratory pathogens.

Objective To investigate the effect of surgical intervention on IVF/ICSI assisted conception outcomes in patients with ovarian endometriosis(OEM).Methods OEM patients who underwent IVF/ICSI treat-ment at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between January 1,2019 and February 1,2024 were selected,including 228 cases in the non-operated group before assisted conception(Group A)and 426 cases in the operated group before assisted conception(Group B),and the assisted concep-tion outcomes of the two groups were analysed.Results There were no statistically significant differences in female age,BMI,infertility years,infertility type,and basal FSH level between the two groups(P＞0.05).AMH level and basal AFC were higher in group A than in group B(P=0.003).There was no statistical difference in the application of ovulation induction programme,total number of Gn days and total amount of Gn between the two groups(P＞0.05),but the amount of Gn initiation in Group A was lower than that in Group B(P=0.011).Applying multiple linear regression to adjust for confounding factors,there was a statistical difference in the 2PN fertilization rate between Groups A and B(P=0.007),whereas there was no statistical difference in the number of eggs obtained,the rate of available embryos,the rate of high-quality embryos and the rate of blastocyst formation between the two groups(P＞0.05).After applying binary logistic regression to adjust for the influencing factors related to clinical pregnancy rate and live birth rate,the clinical pregnancy rate(aOR=-0.896,95％CI:0.540～1.488),live birth rate in the two groups(aOR=0.976,95％CI:0.589～1.620)remained statistically indistin-guishable.Conclusions Surgical intervention may further impair ovarian reserve function in patients with OEM,but does not appear to affect embryo quality or pregnancy outcome.Surgical treatment prior to assisted conception may improve fertilization rates in patients with OEM.

Objective To mine and analyze adverse drug events(ADEs)signals in minors using recombinant human growth hormone(rhGH),and to provide reference for clinically safe use of drugs.Methods Based on the the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data of ADE reports related to rhGH from the third quarter of 2014 to the second quarter of 2024 were retrieved.The ADE reports were standardized and categorized using the Medical Dictionary for Regulatory Activities(MedDRA).The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were employed to mine and analyze ADE signals between rhGH and individuals under 18 years of age.Results A total of 33,642 ADE reports related to the use of rhGH in minors were retrieved.After excluding signals unrelated to ADEs(product issues,social issues,etc.),358 ADE signals were ultimately identified,involving 21 system organ lasses(SOCs).The most frequently reported ADEs were general disorders and administration site reactions(3,621 cases),as well as various laboratory test abnormalities(3,259 cases).Notably,ADE signals related to cardiovascular system tests,psychiatric disorders,and reproductive system and breast disorders,such as decreased serum creatinine,elevated alkaline phosphatase,reduced red blood cell distribution width,crying,aggression,and hypogonadism,were not documented in the drug package insert.Conclusion When administering rhGH to minors,in addition to monitoring common ADEs such as changes in blood glucose levels and scoliosis,attention should also be given to potential ADEs,including alterations in hematological parameters,psychiatric issues,and reproductive system and breast disorders,to ensure medication safety.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective:To investigate the impact of different luteal phase support protocols on pregnancy outcomes in patients aged ≤35 years undergoing modified natural cycle frozen-thawed embryo transfer (mNC-FET).Methods:A retrospective cohort study was conducted to analyze 2 086 cycles of patients aged ≤35 years who received mNC-FET cycles in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020. The cycles were divided into three groups based on luteal phase support protocols used. The patients received a combination of progesterone soft capsule and dydrogesterone in the group A (446 cycles), the patients received dydrogesterone in the group B (439 cycles), and the patients received a combination of progesterone vaginal sustained-release gel and dydrogesterone in the group C (1 201 cycles). The pregnancy and perinatal outcomes were compared between groups A and B, groups C and B after matching the baseline data in a ratio of 1∶1 using the propensity score matching (PSM). The effect of different luteal phase support on live birth rate was analyzed after adjusting for confounding factors affected by univariate and multivariate generalized estimating equation (GEE).Results:After PSM, there were no significant differences between groups A and B, groups C and B in human chorionic gonadotropin positive rate, clinical pregnancy rate, ectopic pregnancy rate, live birth rate in transplant cycle, incidence of low weight, macrosomia, premature delivery rate, pregnancy complication rate and incidence of birth defects (all P>0.05). GEE analysis showed that three different luteal phase support regimens were not associated with live birth rate. Conclusion:In the mNC-FET cycle, patients aged ≤35 years who chose dydrogesterone alone as luteal phase support drug, had no difference in live birth rate and perinatal outcome between progesterone soft capsules or progesterone vaginal sustained-release gel combined with dydrogesterone, but the outcome still needs to be confirmed by large sample prospective studies.