Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Objective:To investigate the sex difference and symptom correlation of pituitary-thyroid axis and pituitary-adrenal axis function in patients with remitted schizophrenia.Methods:Using cross-sectional study method,243 patients with remitted schizophrenia at Changning District Mental Health Center of Shanghai from January 2019 to September 2021(schizophrenia group)were selected,and healthy individuals who underwent physical examinations during the same period(healthy control group)were also selected.The demographic data and HPT axis,HPA axis neuroendocrine indicators[serum thyroid stimulating hormone(TSH),free triiodothyronine(FT3),free thyroid hormone(FT4),triiodothyronine(TT3),thyroid hormone(TT4),adrenocorticotropic hormone(ACTH),and cortisol(COR)]between healthy control group and schizophrenia group were compared.Gender differences in HPT axis and HPA axis in schizophrenia patients were compared.The correlation between neuroendocrine indicators and gender,disease duration,positive and negative symptom scale(PANSS)scores in patients with schizophrenia were analyzed by linear regression method.Using stratified multiple linear regression,laboratory measured variables and age were included as predictive factors in the model to construct a regression prediction model for hormone levels between schizophrenia and healthy control group,as well as subgroups of schizophrenia gender.Generate receiver operating characteristic(ROC)curves based on the probability values of predictive factors,and determine the predictive value of the logistic regression model using the area under the curve(AUC).Results:TT3,TSH,TT4 in schizophrenia group were lower than those in the healthy control group(P＜0.05),while ACTH and COR were higher than those in the healthy control group(P＜0.05).There was a statistically significant difference in the negative symptom scores,TSH,TT3,FT3,ACTH,and COR levels between the female schizophrenia group and male schizophrenia group(P＜0.05).PANSS,total score of general psychopathology score were positively correlated with COR level,negative symptom score was negatively correlated with FT3 levels(all P＜0.05),but there was no linear relationship among the three(absolute value of r＜0.3).ROC curve results showed that,the schizophrenia hormone level model had good discrimination accuracy,with AUC=0.872(95％confidence interval 0.841-0.904),the optimal threshold(Yoden index)=0.651.ROC curve shows that the male and female subgroups of schizophrenia models also have good discrimination accuracy,with AUC=0.794(95％confidence interval 0.737-0.850)and the optimal cutoff value(Yoden index)=0.495.Conclusion:The changes of active T4 in schizophrenia patients may be one of the possible causes of the chronic pathological changes of schizophrenia.The level of high-functioning T3 hormone is significantly lower in female patients than that in male patients.The hierarchical regression model provides good identification accuracy for remitted schizophrenia and gender subgroups.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Objective:To investigate the sex difference and symptom correlation of pituitary-thyroid axis and pituitary-adrenal axis function in patients with remitted schizophrenia.Methods:Using cross-sectional study method,243 patients with remitted schizophrenia at Changning District Mental Health Center of Shanghai from January 2019 to September 2021(schizophrenia group)were selected,and healthy individuals who underwent physical examinations during the same period(healthy control group)were also selected.The demographic data and HPT axis,HPA axis neuroendocrine indicators[serum thyroid stimulating hormone(TSH),free triiodothyronine(FT3),free thyroid hormone(FT4),triiodothyronine(TT3),thyroid hormone(TT4),adrenocorticotropic hormone(ACTH),and cortisol(COR)]between healthy control group and schizophrenia group were compared.Gender differences in HPT axis and HPA axis in schizophrenia patients were compared.The correlation between neuroendocrine indicators and gender,disease duration,positive and negative symptom scale(PANSS)scores in patients with schizophrenia were analyzed by linear regression method.Using stratified multiple linear regression,laboratory measured variables and age were included as predictive factors in the model to construct a regression prediction model for hormone levels between schizophrenia and healthy control group,as well as subgroups of schizophrenia gender.Generate receiver operating characteristic(ROC)curves based on the probability values of predictive factors,and determine the predictive value of the logistic regression model using the area under the curve(AUC).Results:TT3,TSH,TT4 in schizophrenia group were lower than those in the healthy control group(P＜0.05),while ACTH and COR were higher than those in the healthy control group(P＜0.05).There was a statistically significant difference in the negative symptom scores,TSH,TT3,FT3,ACTH,and COR levels between the female schizophrenia group and male schizophrenia group(P＜0.05).PANSS,total score of general psychopathology score were positively correlated with COR level,negative symptom score was negatively correlated with FT3 levels(all P＜0.05),but there was no linear relationship among the three(absolute value of r＜0.3).ROC curve results showed that,the schizophrenia hormone level model had good discrimination accuracy,with AUC=0.872(95％confidence interval 0.841-0.904),the optimal threshold(Yoden index)=0.651.ROC curve shows that the male and female subgroups of schizophrenia models also have good discrimination accuracy,with AUC=0.794(95％confidence interval 0.737-0.850)and the optimal cutoff value(Yoden index)=0.495.Conclusion:The changes of active T4 in schizophrenia patients may be one of the possible causes of the chronic pathological changes of schizophrenia.The level of high-functioning T3 hormone is significantly lower in female patients than that in male patients.The hierarchical regression model provides good identification accuracy for remitted schizophrenia and gender subgroups.

Objective:To explore the clinical manifestations,pathological features,immunophenotype,as well as diagnosis,treatment and prognosis of patients with CD4-CD56+blastic plasmacytoid dendritic cell neoplasm(BPDCN),in order to further understand the rare disease.Methods:The clinical data,laboratory examinations and treatment regimens of two patients with CD4-CD56+BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed.Results:The two patients were both elderly males with tumor involved in skin,bone marrow,lymph nodes,etc.Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive,while CD4,CD34,TdT,CD3,CD20,MPO and EBER were negative.Flow cytometry of bone marrow demonstrated that CD56,CD123,and CD304 were all positive,while specific immune markers of myeloid and lymphoid were negative.Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens,but prone to rapid relapse.The overall survival of both patients was 36 months and 4 months,respectively.Conclusion:CD4-CD56+BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis.Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy. Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed. Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases (7.7％),and 96 cases (92.3％) developed CRS. Patients with high-risk cytogenetics had a higher risk of developing CRS (P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) had a lower risk of developing CRS (P=0.004). There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS (P=0.006). The highest body temperature varied among patients with different treatment regimens (P=0.001). The decrease in total protein in patients with CRS was more significant than in patients without CRS (P=0.002). Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS (P=0.037). Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion (P=0.013),while IL-6,C-reactive protein (CRP),and serum ferritin (SF) also showed significant increases (P=0.007,P<0.001,P=0.003). Conclusion:High-risk cytogenetics is a risk factor for severe CRS. Long duration of fever is a clinical characteristic of severe CRS. CRP can better reflect the severity of CRS.

Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.
Female ; Animals ; Mice ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Choristoma ; Endometriosis/genetics* ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Signal Transduction ; Body Weight ; Mammals ; PTEN Phosphohydrolase/genetics*