ObjectiveTo explore the mechanism of Xianfang Huomingyin （XFHMY） in the treatment of type Ⅲ prostatitis （CP/CPPS） through network pharmacology， molecular docking， and animal experiments. MethodsThe traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Swiss Target Prediction database were used to screen and sort out the active ingredients and corresponding targets of XFHMY. The potential therapeutic targets of CP/CPPS were collected from online databases， such as the Online Mendelian Inheritance in Man （OMIM）， GeneCards， and DisGeNET. The potential core targets of XFHMY for treating CP/CPPS were further screened by constructing a protein-protein interaction （PPI） network and performing topological analysis. Meanwhile， the DAVID database was chosen to perform enrichment analysis on the intersection targets. On this basis， the AutoDock software was used for molecular docking， and the data was subsequently imported into the GraphPad Prism 8 software to generate a heat map. SD rats were divided into seven groups： A blank group， a sham operation group， a model group， low-， medium-， and high-dose XFHMY groups （3.645， 7.29， 14.58 g·kg^-1）， and a tamsulosin hydrochloride group （0.018 mg·kg^-1）. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in prostate tissue. The inflammatory factor indicators of rats in each group were detected via enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （Real-time PCR） and Western blot were used to evaluate the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and nuclear transcription factor-κB （NF-κB） p65 in prostate tissue. ResultsThe HE staining showed no significant signs of inflammatory cell infiltration in the prostate of the sham operation group compared to the blank group， while the model group had significantly inflammatory cell infiltration. The ELISA results showed that compared to the blank group， TNF-α， IL-1β， and COX-2 in the sham operation group had no significant differences. However， they were significantly higher in the model group （P<0.01）， indicating successful CP/CPPS modeling in rats. Compared with the model group， the low-，medium-and high-dose XFHMY group and the tamsulosin hydrochloride group showed significant decreases in TNF-α， IL-1β， and COX-2 （P<0.05，P<0.01）. The Real-time PCR analysis revealed that compared to the model group， the low-dose XFHMY group had reduced Akt and NF-κB p65 mRNA expression（P<0.05，P<0.01）. In the medium-and high-dose XFHMY group and tamsulosin hydrochloride group， PI3K， Akt， and NF-κB p65 mRNA levels decreased significantly（P<0.05，P<0.01）. Western blot analysis showed that compared to the model group， the low-dose XFHMY group had lower p-NF-κB p65/NF-κB p65 （P<0.05）. The medium- and high-dose XFHMY group and the tamsulosin hydrochloride group showed significant decreases in p-PI3K/PI3K， p-Akt-ser473/Akt， p-Akt-thr308/Akt， and p-NF-κB p65/NF-κB p65 （P<0.01）. ConclusionXFHMY may exert therapeutic efficacy on CP/CPPS by inhibiting the PI3K/Akt/NF-κB signaling pathway and reducing inflammatory responses. Additionally， NF-κB activation may be related to the activation of ser473 and thr308 sites.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

BACKGROUND:Nerve growth factor is a protein that induces nerve growth and regulates biological behaviors such as proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To investigate the promoting effect of nerve growth factor on chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured,and nerve growth factor was transfected into bone marrow mesenchymal stem cells by lentiviral transfection.The effects of nerve growth factor on the proliferation,migration,hypertrophic differentiation,and chondrogenic differentiation of bone marrow mesenchymal stem cells were detected by CCK-8 assay,cell scratch assay,alizarin red staining,and western blot assay,using the transfected null-loaded virus as control.To further investigate the promoting effect of nerve growth factor on the chondrogenic differentiation of bone marrow mesenchymal stem cells,interleukin 1β was added in bone marrow mesenchymal stem cells transfected with empty virus and nerve growth factor for 14 days.The expression of proteins related to chondrogenic differentiation and hypertrophic differentiation was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that nerve growth factor had no significant effect on the proliferation of bone marrow mesenchymal stem cells.(2)Compared with the control group,overexpression of nerve growth factor enhanced the migration ability of the cells,and the expression of cartilage-associated proteins type II collagen and SOX9 was up-regulated(P<0.05),while the expression of hypertrophic-associated proteins type X collagen and Runx2 was down-regulated(P<0.05).(3)Compared with the empty virus+interleukin 1β group,the expression of cartilage-associated proteins type II collagen and Sox9 was up-regulated(P<0.05),and the expression of hypertrophy-associated proteins type X collagen and Runx2 was down-regulated after overexpression of nerve growth factor(P<0.05).(4)The results indicated that nerve growth factor could promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.

Objective To evaluate the effectiveness of thermal tomography in breast cancer (BC) screening. Methods We conducted a general population-based BC screening in three regions of Hubei Province (Xiantao, Hongan, and Yangxin Districts). Participants underwent a questionnaire-based interview for baseline data collection. They then received a physical examination, thermal tomography, and ultrasound from doctors and technicians. We compared the efficacies, including sensitivity, specificity, and false-positive rates, of ultrasound and thermal tomography in BC screening. Results A total of 59 712 eligible women were included in this screening program. The BI-RADS 1, 2, 3, 4, and 5 accordance rates between the two screening methods were 0.9549, 0.8047, 0.9037, 0.3352, and 0, respectively. The overall accordance rate was 0.933 1. The kappa consistency results showed that the Cicchetti-Allison and Fleiss-Cohen kappa values were 0.7970 and 0.8583, respectively. Although the two methods had equal sensitivities, specificity was higher in thermal tomography than in ultrasound. The false-positive rate was lower in thermal tomography than in ultrasound. The area under the receiver operating characteristic (ROC) curve of thermal tomography was significantly larger than that of ultrasound. Conclusion The general consistency between thermal tomography and ultrasound in BC screening was high. Thermal tomography outperformed ultrasound in terms of specificity and diagnostic efficiency. Therefore, thermal tomography has a high application value for general population-based BC screening.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective To explore the relationship between serum soluble semaphorin 4D(sSema4D),CXC chemokine ligand 12(CXCL12)levels and left ventricular diastolic function in young and middle-aged patients with essential hypertension.Methods A total of 148 young and middle-aged patients with essential hyperten-sion admitted to a hospital from November 2020 to November 2022 were selected as the study subjects,and were grouped into left ventricular diastolic dysfunction group(n=41)and normal left ventricular diastolic function group(n=107)according to their left ventricular diastolic function.The serum levels of sSema4D and CXCL12 were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis was applied to analyze the correlation between the serum levels of sSema4D and CXCL12 and the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular septal thickness(IVST),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVEF),E peak/A peak(E/A)and maximum velocity of tricuspid regurgitation(TRVmax).The predictive value of ser-um sSema4D and CXCL12 levels in left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension was analyzed by receiver operating characteristic(ROC)curve.Results There were significant differences in diastolic blood pressure and gender between the left ventricular diastolic dys-function group and the left ventricular diastolic function normal group(P＜0.05).Compared with the normal left ventricular diastolic function group,serum levels of sSema4D,CXCL12 in the left ventricular diastolic dys-function group were obviously increased,and the difference was statistically significant(P＜0.05).Compared with normal left ventricular diastolic function group,IVST and LVPWT in the left ventricular diastolic dys-function group were significantly increased,and E/A was significantly decreased,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum sSema4D and CXCL12 levels were positively cor-related with LVEDD,IVST and LVPWT(P＜0.05),and negatively correlated with E/A(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of serum sSema4D and CXCL12 combined in pre-dicting left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension was 0.894(95％CI:0.833-0.939),which was significantly greater than that of sSema4D alone in predicting left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension(Z=3.142,P=0.002)and CXCL12 alone predicted the AUC of left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension(Z=3.268,P=0.001).Conclusion Serum sSema4D and CXCL12 levels are associated with left ventricular diastolic function in young and middle-aged patients with essential hypertension.

Nonalcoholic fatty liver disease （NAFLD） is an abnormal lipid metabolic disorder of the liver characterized by accumulation of a large amount of lipids in the liver， and it is currently the most common liver disease around the world. Mendelian randomization （MR） incorporates genomic data into traditional epidemiological study designs to infer the causal relationship between exposure factors and disease risk. In recent years， MR has been widely used in studies on inference of the etiology of NAFLD. This article systematically summarizes the advances in the application of MR in NAFLD research， so as to provide new ideas for understanding the nature of the disease and scientific interventions.

【Objective】 To investigate the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (M-TESE) in patients with non-obstructive azoospermia (NOA) caused by different causes. 【Methods】 A retrospective analysis was performed on 225 NOA patients during Jan.2020 and Dec.2022. The relation between SRR and patients’ age,body mass index (BMI),testicular volume,endocrine hormones and different etiological classifications were analyzed. 【Results】 According to whether sperm was obtained by surgery,the patients were divided into two groups,including 107 cases in the sperm group and 118 cases in the non-sperm group. There were no significant differences in patients’ age,testicular volume and levels of endocrine hormones between the two groups (P>0.05). According to the different causes,NOA patients with mumps history,cryptorchidism history,AZFc deletion or Klinefelter syndrome (KS) had higher SRR,while idiopathic NOA patients had the lowest SRR (P<0.05). 【Conclusion】 M-TESE is an effective treatment of NOA. There is no correlation between SRR and patients’ age,MBI,testicular volume and levels of endocrine hormones. NOA caused by different etiological classifications may have different SRR.

【Objective】 To investigate the effects of the loss of exon 1 of TFE3 on nuclear localization of chimeric TFE3 protein in TFE3 translocation renal cell carcinoma (TFE3 tRCC). 【Methods】 The localization of TFE3 protein in TFE3 tRCC and clear cell renal cell carcinoma (ccRCC) were detected with immunochemistry. The exon retention of TFE3 gene in TFE3 tRCC was analyzed in databases and literatures. The plasmids containing TFE3 full-length and different-length of TFE3 exons which were constructed to pCDH-MCS-EGFP-Puro were transfected into HEK293T using Lipo Fiter^TM. The localization of EGFP protein in HEK293T cells were detected with confocal microscopy. The localization of TFE3 protein and truncated TFE3 protein were detected with Western blotting. The mRNA expression of the downstream genes of TFE3 protein were detected with q-PCR. 【Results】 Strong nuclear signal of TFE3 protein was observed in TFE3 tRCC, whereas TFE3 protein in ccRCC was mainly localized in cytoplasm. The results of fluorescence imaging and Western blotting showed that TFE3 full-length protein was expressed both in nucleus and cytoplasm, and the expression of truncated TFE3 protein was mainly localized in nucleus. The q-PCR analysis demonstrated that the deletion of exon 1 in TFE3 gene led to a higher transcriptional level of targeted genes of TFE3 protein. 【Conclusion】 The loss of exon 1 in TFE3 played a critical role in preventing TFE3 protein from entering the nucleus. In TFE3 tRCC, the loss of exon 1 in TFE3 gene leads to the nuclear localization of TFE3 fusion protein and activation of its downstream target genes. This mechanism promises to uncover the occurrence and development of TFE3 tRCC.

Objective:To investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy combined with targeted therapy.Methods:The clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII) and prognostic nutritional index (PNI). According to the optimal cut-off values, the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis.Results:By the end of follow-up, 74 patients died and 46 survived. The median follow-up time was 23.0 months, the median overall survival (mOS) was 15.6 months, and the median progression-free survival (mPFS) was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR, PLR, SII, LMR and PNI were 3.45, 131.87, 626.21, 2.12 and 43.30, respectively. The mPFS (18.3 months vs. 8.7 months) and mOS (26.6 months vs. 10.9 months) of patients in the low-NLR group ( n=75) were longer than those of the high-NLR group ( n=45), and there were statistically significant differences ( χ2=55.64, P<0.001; χ2=64.14, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (24.5 months vs. 13.5 months) of patients in the low-PLR group ( n=55) were longer than those of the high-PLR group ( n=65), and there were statistically significant differences ( χ2=5.27, P=0.023; χ2=11.84, P<0.001). The mPFS (18.0 months vs. 10.7 months) and mOS (25.7 months vs. 12.8 months) of patients in the low-SII group ( n=75) were longer than those of the high-SII group ( n=45), and there were statistically significant differences ( χ2=24.46, P<0.001; χ2=25.42, P<0.001). The mPFS (18.2 months vs. 10.9 months) and mOS (26.6 months vs. 13.2 months) of patients in the high-LMR group ( n=56) were longer than those of the low-LMR group ( n=64), and there were statistically significant differences ( χ2=19.25, P<0.001; χ2=19.92, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (25.4 months vs. 13.4 months) of patients in the high-PNI group ( n=62) were longer than those of the low-PNI group ( n=58), and there were statistically significant differences ( χ2=13.69, P<0.001; χ2=19.07, P<0.001). Univariate analysis showed that Barcelona clinic liver cancer (BCLC) stage ( HR=1.83, 95% CI: 1.17-2.87, P=0.008), Child-Pugh grade ( HR=2.21, 95% CI: 1.47-3.34, P<0.001), modified albumin-bilirubin (mALBI) grade ( HR=1.35, 95% CI: 1.01-1.81, P=0.045), extrahepatic metastases ( HR=2.18, 95% CI: 1.47-3.25, P<0.001), NLR ( HR=1.40, 95% CI: 1.28-1.54, P<0.001), PLR ( HR=1.00, 95% CI: 1.00-1.01, P=0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P<0.001), LMR ( HR=0.64, 95% CI: 0.51-0.79, P<0.001) and PNI ( HR=0.95, 95% CI: 0.93-0.98, P=0.001) were correlated with PFS; BCLC stage ( HR=2.18, 95% CI: 1.21-3.91, P=0.009), Child-Pugh grade ( HR=2.57, 95% CI: 1.61-4.09, P<0.001), Eastern Cooperative Oncology Group performance status score ( HR=1.59, 95% CI: 1.01-2.51, P=0.044), mALBI grade ( HR=1.60, 95% CI: 1.17-2.17, P=0.003), extrahepatic metastasis ( HR=2.51, 95% CI: 1.59-3.96, P<0.001), NLR ( HR=1.45, 95% CI: 1.32-1.60, P<0.001), PLR ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), SII ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), LMR ( HR=0.57, 95% CI: 0.40-0.72, P<0.001) and PNI ( HR=0.92, 95% CI: 0.89-0.96, P<0.001) were correlated with OS. Multivariate analysis showed that extrahepatic metastasis ( HR=1.78, 95% CI: 1.10-2.87, P=0.018) and NLR ( HR=1.46, 95% CI: 1.24-1.73, P<0.001) were independent influencing factors for PFS; extrahepatic metastasis ( HR=2.09, 95% CI: 1.21-3.61, P=0.009), NLR ( HR=1.56, 95% CI: 1.29-1.88, P<0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P=0.025), LMR ( HR=0.59, 95% CI: 0.45-0.78, P=0.008) and PNI ( HR=0.93, 95% CI: 0.88-0.99, P=0.013) were independent influencing factors for OS. Conclusion:NLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy, and NLR, SII, LMR, PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR, high SII, low LMR, low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients.