BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Objective To investigate the lipid-lowering efficacy and safety of Xuezhikang combined with PCSK9 inhibitor in patients with coronary heart disease.Methods A total of 102 patients with coronary heart disease hospitalized in Jiangxi Provincial People's Hospital from June 2023 to November 2024 were enrolled in this study and randomly divided into a control group(50 cases)and an experimental group(52 cases).The control group received basic medication for secondary prevention of coronary heart disease,while the experi-mental group received Xuezhikang combined with PCSK9 inhibitor in addition to the basic medication.After 6 months of treatment,blood lipid indicators,liver function indicators,kidney function indicators,incidence of major adverse cardiovascular events(MACE),and incidence of adverse drug reactions were observed.Results After treatment,LDL-C,TC,AST,and ALT levels decreased in both groups compared with before treatment.The experimental group showed significantly lower levels of these indicators than the control group,with statistically significant differences(P<0.05).Both groups had one case of adverse drug reaction each,showing no statistically significant difference(P>0.05).The MACE incidence was higher in the control group than in the experimental group(18.0%vs.3.8%,P<0.05).The lipid goal achievement rate was low-er in the control group than in the experimental group(44.0%vs.73.1%,P<0.05).Conclusion The com-bination of Xuezhikang and PCSK9 inhibitors demonstrates definite clinical efficacy in coronary heart disease patients,reduces MACE risk,and improves lipid goal achievement rates.

Objective To develop an instrument for predicting postoperative constipation risks in patients with osteoporotic thoracolumbar fracture(OTLF)who have undergone percutaneous kyphoplasty(PKP).Methods A total of 858 OTLF patients who underwent PKP surgery between January 2020 and December 2024 were enrolled.The patients were randomly assigned to a training set(n=600)and a validation set(n=258)in a 7∶3 ratio.According to whether the patients had postoperative constipation,the training set was divided into a constipation group(n=205)and a non-constipation group(n=395),and the validation set was divided into a constipation group(n=90)and a non-constipation group(n=168).Logistic regression analysis was conducted to analyze the factors influencing postoperative constipation in OTLF patients after PKP,and a nomogram model was constructed accordingly.The receiver operating characteristic(ROC)curve and the calibration curve of the model were plotted,and the Hosmer-Lemeshow test for goodness of fit was performed.Results A total of 205 OTLF patients(34.17%)in the training set and 90 OTLF patients(34.88%)in the validation set experienced constipation after PKP.Univariate analysis revealed significant differences between the constipation and non-constipation groups in terms of operative time,postoperative water intake,time to first postoperative meal,postoperative bed rest time,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the Nutrition Risk Screening 2002(NRS-2002)score,and the levels of sodium,potassium,and HbA1c(P<0.05).Least absolute shrinkage and selection operator(LASSO)regression was performed and operative time,time to first postoperative meal,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the NRS-2002 score,and the levels of sodium,potassium,and HbA1c were identified as candidate predictors.Multivariate logistic analysis showed that the time to first postoperative meal,the levels of Bifidobacterium and Lactobacillus,the NRS-2002 score,and the levels of sodium and HbA1c were influencing factors of postoperative constipation in OTLF patients(P<0.05).The ROC curves showed that the area under the curve(AUC)of the training set was 0.842(95%CI:0.793-0.892),while that of the validation set was 0.860(95%CI:0.830-0.889).The calibration curves demonstrated good agreement between the prediction curve and the standard curve in both the training set and the validation set.Conclusion The time to the first postoperative meal,the NRS2002 score,and the levels of Bifidobacterium,Lactobacillus,sodium,and HbA1c are influencing factors of post-PKP constipation in OTLF patients.The nomogram model built based on these factors exhibited good predictive performance.

OBJECTIVE To establish an ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of dexmedetomidine(DEX)in plasma of beagle dogs and evaluate the pharmacokinetics and sedation after nasal,buccal and sublingual mucosal admin-istration.METHODS A UPLC-MS/MS method was established and validated for dertermination of DEX in plasma of beagle dogs.DEX was administered to the nasal cavity,buccal and sublingual mucous membranes of beagle dogs,respectively.Blood samples were collected at different time points.The plasma concentration of DEX was measured by the established UPLC-MS/MS method.Pharmacokinetic parameters were fitted by Phoenix software and the sedative effect at different mucous membrane sites was evaluated in conjunction with behavioral and Ramsay scores.RESULTS The linearity of DEX was fine within the range of 0.05-100 μg·L-1(r>0.999),which was validated methodologically to meet the requirements of quantitative detection.The plasma concentration of the drug peaked the fastest with nasal administration.Tmax was 0.25 h,Cmax(4.43±1.19)μg·L-1,and the AUC0-6h was(8.92±2.07)μg·h·L-1,compared with 0.92 and 1 h,(2.87±0.69),(2.70±0.41)μg·L-1,and(7.99±1.77),(7.01±2.09)μg·h·L-1 with buccal and sublingual administration.Nasal administration had the fastest onset at 7 min,with a Ramsay score of 4,and sedation lasted for 36 min,compared with 33 and 35 min,and 38 and 37 min for buccal and sublingual administration.CONCLUSION The proposed method is sensitive,reliable and applicable to quantitative analysis of DEX in plasma of beagle dogs.Administration of DEX to the nasal cavity mucosa has a faster onset and a better sedative effect than to the buccal and sublingual mucosa.

Objective:To describe the epidemiological characteristics of 22 common respiratory patho-gens in patients with pneumonia in Yinzhou,Ningbo,from January 1,2015 to December 21,2024.Methods:The test data of 22 common respiratory pathogens in patients diagnosed with pneumonia or lung infection in the Yinzhou Regional Health Information Platform from January 1,2015 to December 21,2024 were collected.The positive cases,positive rates,and positive proportions were calculated.The epidemiological characteristics were described by the year,sex,age group,season,and coronavirus disease 2019(COVID-19)pandemic period.Results:A total of 77 531 pneumonia patients were included,with 492 696 respiratory pathogen tests performed.The number of respiratory pathogen tests and positive cases of pneumonia patients in Yinzhou showed an upward trend.In the study,34.63％of the pneumo-nia patients tested positive for at least one pathogen,and the pathogen non-detection rate decreased from 79.44％in 2015 to 58.38％in 2024.The overall pathogen positive rate was 9.12％,which decreased during the COVID-19 pandemic and had not returned to the historical level after the COVID-19 pande-mic.The positive rate was highest in children aged 6-17 years(13.99％),and lowest in the elderly over 60 years(4.16％).The top 3 highest number of positive cases was Mycoplasma pneumoniae,influenza A virus,and influenza B virus;the top 3 highest positive rates of pathogen tests were Mycoplasma pneu-moniae(25.26％),rhinovirus(12.02％),and Bordetella pertussis(11.66％).The pathogen spectrum proportion in men was similar to that in women,only showing a higher ratio of Mycobacterium tuberculosis and a slightly lower ratio of Mycoplasma pneumoniae(P＜0.001).Mycoplasma pneumoniae,respiratory syncytial virus,and rhinovirus infections were more common in children,while influenza virus,Mycobac-terium tuberculosis,and Streptococcus pyogenes infections were more common in adults and the elderly(P＜0.001).Influenza virus and human metapneumovirus infections were more common in winter,rhi-novirus and Bordetella pertussis infections were more common in spring,and Mycoplasma pneumoniae in-fections were relatively more common in fall(P＜0.001).After the COVID-19 pandemic,the propor-tions of rhinovirus,respiratory syncytial virus,and human metapneumovirus infections in the pneumonia patients increased signi-ficantly,reaching 7.53％,4.26％,and 2.25％,respectively,while the propor-tions of influenza B virus and Mycobacterium tuberculosis infections decreased to 4.14％and 2.80％,re-spectively(P＜0.001).Conclusion:In the past decade,the scale of respiratory pathogen infection in the pneumonia population in Yinzhou had expanded significantly,and there were differences in distribu-tion by the year,gender,age group,and season.The respiratory pathogen spectrum in pneumonia pa-tients after the COVID-19 pandemic had a trend of diversification.

Purpose To explore the feasibility and clinical value of deep learning-based image reconstruction technology in 5.0T MRI for nasopharyngeal carcinoma.Materials and Methods A prospective study was conducted on 50 newly diagnosed nasopharyngeal carcinoma patients from August to December 2024 at Sun Yat-sen University Cancer Center.5.0T MRI was performed to scan the nasopharynx region.Routine scanning protocols included transverse T2WI,transverse T1WI,transverse contrast-enhanced T1WI and coronal fat-suppressed contrast-enhanced T1WI sequences.Based on these standard scanning protocols,DeepRecon deep learning reconstruction technology with different levels(grade 1-5)was applied,generating a total of 24 sets of images.Qualitative evaluation employed a Likert scale(5-point system)for subjective scoring on lesion detection,lesion edge clarity,artifacts and overall image quality.Quantitative evaluation was performed using the signal-to-noise ratio and contrast-to-noise ratio to objectively assess the quality of the 24 image sets.Differences in qualitative and quantitative indicators between different groups were compared,while the Kappa coefficient was used to analyze the consistency of subjective evaluations by two radiologists.Results In the qualitative assessment of 24 image sets from four MRI sequences(with and without DeepRecon reconstruction),DeepRecon images(grade 2-4)significantly outperformed traditional images in all features except for artifact reduction(Z=-12.11--6.23,all P<0.001).Images reconstructed at DeepRecon grade 3 had the highest overall score and the best image quality.Furthermore,compared with traditional images,DeepRecon images(grade 2-5)demonstrated significantly improved signal-to-noise ratio for both lesions and the lateral pterygoid muscle(t=-15.67--3.44,Z=-6.09--4.63,all P<0.01).In addition,in the transverse T2WI,transverse contrast-enhanced T1WI and coronal fat-suppressed contrast-enhanced T1WI images with DeepRecon reconstruction(grade 2-5),the contrast-to-noise ratio(lesion/lateral pterygoid muscle)also showed significant improvement compared to traditional images(t=-12.71--3.19,Z=-6.08--4.47,all P<0.001).The inter-observer agreement for the overall subjective quality score between the two radiologists was good(Kappa=0.75-0.82,all P<0.01).Conclusion DeepRecon deep learning reconstruction technology significantly increases the signal-to-noise ratio and resolution of traditional magnetic resonance images of nasopharyngeal cancer,improving image clarity and bringing more possibilities for the advancement of imaging diagnosis.

Objective To investigate the application effect of high flow humidified oxygen therapy combined with tracheotomy in elderly patients with cerebral hemorrhage and analyze the risk factors of pulmonary infection.Methods A total of 140 elderly patients with cerebral hemorrhage who underwent tracheotomy in our hospital from 2019 to 2023 were selected as the study objects,of which 93 patients receiving high-flow humidified oxygen therapy were selected as the observation group,and 47 patients receiving conventional low-flow oxygen therapy were selected as the control group during the same period.The changes of PaO2,SpO2,heart rate and mean arterial pressure were compared,and patients in the observation group were divided into infected group(n=26)and non-infected group(n=67)according to whether pulmonary infection occurred during hospitalization.The risk factors affecting pulmonary infection during hospitalization in elderly patients with cerebral hemorrhage were analyzed,and a nematographic prediction model was built to predict the risk of pulmonary infection.Results The PaO2 and SpO2 levels in observation group were higher than those in control group at 24 h and 72 h,but the respiratory rate was lower than that in control group(P＜0.05).The improvement of sputum viscosity in the observation group(68 cases of grade Ⅰ sputum and 25 cases of grade Ⅱ sputum)was better than that in the control group(16 cases of grade Ⅰ sputum,17 cases of grade Ⅱ sputum and 14 cases of gradeⅢ sputum).The rate of phlegm scab formation(0)and the number of sputum aspiration(5.15±1.08)times were lower than those in the control group[14.87％,(8.17±1.82)times](P＜0.05).There were significant differences in tracheotomy time,smoking history,bed rest time,mechanical ventilation time and nasal feeding tube retention time between infected and non-infected groups(P＜0.05).Logistic regression analysis showed that tracheotomy time＞5 d,smoking history,bed time＞10 d,mechanical ventilation time ≥24 h,nasal feeding tube retention time≥10 d were the risk factors for pulmonary infection in elderly patients with cerebral hemorrhage during treatment(P＜0.05).The AUC,sensitivity and specificity were 0.696,0.565 and 0.889 in elderly patients with cerebral hemorrhage complicated by pulmonary infection during treatment.Conclusion High-flow humidification oxygen therapy combined with tracheotomy can improve the oxygenation status in elderly patients with cerebral hemorrhage,but the time of tracheotomy,smoking history,bed rest time,mechanical ventilation time,and nasal feeding tube retention time will affect the pulmonary infection during treatment.The construction of a nomogram model based on these risk factors has higher predictive efficacy in evaluating the pulmonary infection.

Objective:To analyze the prognostic influencing factors in patients with isocitrate dehydrogenase (IDH) wild-type glioma, and further evaluate the value of surgical resection in prognosis.Methods:The clinical data and molecular pathological information of 647 patients with IDH wild-type glioma were retrieved from the Chinese Glioma Genome Atlas (CGGA) database (from 2006 to 2019). The clinical characteristics were recorded, including gender, age, initial symptoms, preoperative Karnofsky performance status (KPS) score, tumor location, tumor laterality, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and postoperative treatment. Kaplan-Meier survival curve was plotted to calculate overall survival (OS) and progression-free survival (PFS), and comparisons were performed using the log-rank test. Multivariate Cox regression analysis was used to identify the independent influencing factors of prognosis in patients with IDH wild-type glioma.Results:Among the 647 patients with IDH wild-type glioma, there were 120 cases of WHO grade Ⅱ, 115 cases of grade Ⅲ, and 412 cases of grade Ⅳ; the median OS was 20.3 months. There were statistical differences in age, initial symptoms, tumor location, preoperative KPS score, extent of resection, MGMT promoter methylation status and postoperative treatment among patients with different WHO grades (P<0.01), but there were no statistical difference in gender and tumor laterality (P>0.05). The median OS and PFS in patients with WHO grade Ⅱ were significantly longer than those in patients with WHO grade Ⅲ and WHO grade Ⅳ (169.9 months vs. 24.7 and 14.4 months, 138.8 months vs. 17.7 and 11.4 months), the indexes in patients with WHO grade Ⅲ were significantly longer than patients with WHO grade Ⅳ, and there were statistical differences (P<0.05). The median OS and PFS in patients with total resection were significantly longer than those in patients with subtotal resection and partial resection (37.2 months vs. 20.3 and 8.5 months, 29.5 months vs. 17.6 and 6.0 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 153 patients with MGMT promoter methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (67 cases) were significantly longer than those in patients with subtotal resection (64 cases) and partial resection (22 cases): 28.8 months vs. 18.4 and 9.0 months, 25.6 months vs. 16.6 and 6.5 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 202 patients with MGMT promoter non-methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (81 cases) were significantly longer than those in subtotal resection (81 cases) and partial resection (40 cases): 31.3 months vs. 21.9 and 14.0 months, 22.7 months vs. 16.8 and 9.7 months, and there were statistical differences (P<0.05), but there were no statistical difference in the indexes between patients with subtotal and patients with partial resection (P>0.05). Multivariate Cox regression analysis result showed that age, extent of resection, WHO grade (grade Ⅲ/grade Ⅳ) and postoperative treatment were independent OS and PFS influencing factors in patients with IDH wild-type glioma (OS: HR = 1.327, 3.295, 3.406/7.964 and 1.597; 95% CI 1.079 to 1.633, 2.627 to 4.132, 2.225 to 5.216/5.339 to 11.880 and 1.288 to 1.981; P<0.01. PFS: HR = 1.282, 2.655, 3.143/6.511 and 1.477; 95% CI 1.039 to 1.583, 2.123 to 3.322, 2.049 to 4.819/4.376 to 9.690 and 1.181 to 1.849; P<0.05 or <0.01).Conclusions:The age, extent of resection, WHO grade and postoperative treatment are independent prognosis influencing factors in patients with IDH wild-type glioma. Treatment strategies should fully consider the clinical and molecular pathological characteristics to achieve maximal safe tumor resection and optimal survival benefit.