Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective To investigate the underlying mechanism of Hongyu Decoction in the treatment of inflammatory bowel disease(IBD)based on serum amino acid metabolism.Methods A total of 50 male C57BL/6J mice were divided into control group,model group,sulfasalazine(SASP)group and Hongyu Decoction low-and high-dosage groups,with 10 mice in each group.Except for the control group,the rest groups were treated with 3%dextran sulfate sodium freely for seven consecutive days to establish the IBD model.The SASP group was given SASP solution at a dosage of 200 mg/kg by gavage,while the Hongyu Decoction low-and high-dosage groups were given Hongyu Decoction freeze-dried powder solution at dosages of 0.5 and 2.0 g/kg respectively by gavage for 11 consecutive days.The general condition was monitored and DAI score were calculated.After the mice were sacrificed,the length of colons was measured,ELISA was used to detect serum TNF-α,IL-1β,IL-17 contents,HE staining was used to observe the morphology of colon tissue,and Alizarin blue staining was used to evaluate the secretion of mucin levels by intestinal epithelial goblet cells,UPLC-MS and multivariate statistical methods were used to analyze the serum amino acid metabolism profiles of mice in the control group,model group and Hongyu Decoction high-dosage group,and differential amino acids were screened.Pathway enrichment analysis was performed on differential amino acids using MetaboAnalyst 5.0.Results Compared with the control group,the DAI score of the model group mice significantly increased(P<0.001),the colon length was significantly shortened(P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 significantly increased(P<0.001);with widespread ulceration of colon tissue,disappearance of mucosal epithelium and intestinal crypt structure,infiltration of lymphocytes and neutrophils,congestion and edema of intestinal mucosa,proliferation of submucosal connective tissue,reduced number of colonic goblet cells and mucin secretion.Compared with the model group,the Hongyu Decoction high-dosage group showed a significant decrease in DAI score(P<0.001),while the SASP group and the Hongyu Decoction low-and high-dosage groups showed a significant increase in colon length(P<0.05,P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 were significantly reduced(P<0.001);the colonic villi were relatively intact,the glands were clear and arranged neatly,the branches of the intestinal crypts were obvious,no obvious edema was observed,and the number of colonic goblet cells and mucin secretion increased.Seven potential biomarkers for IBD in mice were identified through serum metabolomics screening,including tryptophan,serine,glutamate,valine,histidine,methionine and phenylalanine;two potential biomarkers for the treatment of IBD with Hongyu Decoction were identified,namely valine and tyrosine.The results of pathway enrichment analysis showed that the differential amino acids in the model group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,histidine metabolism,cysteine and methionine metabolism,phenylalanine metabolism and arginine biosynthesis;the differential amino acids in Hongyu Decoction high-dosage group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of alanine,aspartate and glutamate,and the biosynthesis of arginine.Conclusion Hongyu Decoction can improve intestinal epithelial damage and inflammatory cell infiltration in IBD mice,protect the integrity of the intestinal mucosal barrier,and may be related to regulating amino acid metabolism in the body.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Ovarian follicle expansion is an important part of their growth and development into dominant follicles,and is regulated by a variety of molecules and signals,including follicular cavity formation,follicular fluid accumulation,and granulosa cell proliferation.Polycystic ovary syndrome(PCOS)is the most common reproductive endocrine disease in women,and patients mainly present with increased preantral follicles and polycystic ovarian lesions caused by inadequate ovarian follicle expansion.This review summarizes recent research developments concerning the physiological process of ovarian follicle expansion and the related regulatory factors and mechanisms.We also consider the possible factors restricting ovarian follicle expansion in patients with PCOS,to provide a theoretical basis for follicular dysplasia,ovulation disorders and other diseases caused by abnormal ovarian follicle expansion.

Objective:To evaluate the long-term clinical efficacy and the influence on anal function of surgery combined with ustekinumab (UST) in active Crohn's disease (CD) patients with perianal fistula.Methods:A retrospective cohort study was conducted. Clinical data of active CD patients with perianal fistula undergoing surgery combined with UST at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from August 2020 to December 2022 were collected. The primary endpoints were clinical healing rate, Wexner score, and anorectal manometry values at week 52 of treatment. Secondary endpoints included the Crohn's disease activity index (CDAI), perianal Crohn's disease activity index (PDAI), laboratory indicators [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) ], endoscopic remission rate, Van Assche score, and radiographic healing rate at week 52 of treatment.Results:A total of 28 patients were included, with 22 males (78.6%) and 6 females (21.4%) ; age (25.2 ± 7.7) (16.0-52.0) years. There was 1 patient (3.6%) of simple anal fistula. There were 27 patients (96.4%) of complex anal fistulas, including 12 of high intersphincteric type, 15 of high transsphincteric type, in which 15 with branched tracts (or ≥2 fistula tracts). The pre-treatment CDAI was 187.0 (156.0, 245.0), and the PDAI was 10.0 (9.0, 12.0). Among the 28 patients, 23 (82.1%) underwent fistulotomy, 1 (3.6%) underwent transanal opening of intersphincteric space (TROPIS), and 4 (14.3%) underwent video-assisted anal fistula treatment (VAAFT) combined with fistula-tract laser closure (FiLaC). All the patients received UST treatment postoperatively, without concurrent use of immunosuppressants or corticosteroid therapy. At week 52 of treatment, 28 (100%) patients achieved clinical healing. Compared to pre-treatment, Wexner score of patients at week 52 of treatment was significantly lower [0 (0, 0) vs. 1.0 (0, 3.0), P < 0.001], maximum anal sphincter pressure increased [ (137.6±40.9) mmHg vs. (105.1±29.2) mmHg, P < 0.001], maximum anal sphincter contraction time extended [9.0 (5.0, 15.0) s vs. 4.0 (2.0, 6.0) s, P < 0.001], and there was no significant decrease in anal resting pressure ( P > 0.05). Compared to pre-treatment, CDAI, PDAI, Van Assche scores, and simple endoscopic score for Crohn's disease (SES-CD) of patients at week 52 of treatment all significantly decreased (all P < 0.001), and CRP, ESR, and FC all decreased (all P < 0.05), with statistically significant differences. The radiographic healing rate at week 52 of treatment was 75.0% (21/28), and the radiographic remission rate was 92.9% (26/28). The endoscopic remission rate was 57.1% (16/28), and the endoscopic response rate was 82.1% (23/28) . Conclusion:The long-term clinical healing rate of active CD patients with perianal fistula receiving surgery combined with UST is high, and the anal function can be improved significantly.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To construct a prediction model for targeted biopsy(TB)of the prostate based on multiparameter magnetic resonance imaging(mp-MRI)and prostate-specific antigen density(PSAD)to predict the outcomes TB in patients with a score of 4-5 on the Prostate Imaging Reporting and Data System(PI-RADS).Methods Clinical data of 669 patients with PI-RADS 4-5 receiving transperineal TB in our hospital during Jan.2022 and Dec.2023 were retrospectively analyzed.The data were divided into the training set and validation set with a ratio of 2∶1.Independent predictors of TB results were identified with univariate and multivariate logistic regression to construct a formula for the prediction model.A prediction model was subsequently constructed and validated using the validation set to assess its efficacy and predictive performance with the area under the receiver operating characteristic curve(AUC).The relative importance of each independent predictor in the formula was analyzed.Results Univariate and multivariate logistic regression analyses showed that age,total number of lesions,histological location,PI-RADS score and PSAD were significantly associated with the TB outcomes(P＜0.05)and could be used as independent predictors,with PI-RADS score and PSAD making the highest contribution to outcome prediction,accounting for 27.59％and 37.58％,respectively.The training set had an AUC of 0.840(95％CI:0.800-0.881),which was more predictive than other single predictors,and the high-risk group based on the optimal threshold of 0.833 increased the positive biopsy rate from 79.3％to 94.4％.The validation set had an AUC of 0.865(95％CI:0.810-0.920),and the high-risk group based on the optimal threshold of 0.594 increased the positive biopsy rate from 80.0％to 96.2％.Conclusion The prediction model has good predictive ability for lesions with PI-RADS 4-5,which can significantly improve the positive detection rate and reduce a large number of unnecessary systematic puncture.

Ovarian follicle expansion is an important part of their growth and development into dominant follicles,and is regulated by a variety of molecules and signals,including follicular cavity formation,follicular fluid accumulation,and granulosa cell proliferation.Polycystic ovary syndrome(PCOS)is the most common reproductive endocrine disease in women,and patients mainly present with increased preantral follicles and polycystic ovarian lesions caused by inadequate ovarian follicle expansion.This review summarizes recent research developments concerning the physiological process of ovarian follicle expansion and the related regulatory factors and mechanisms.We also consider the possible factors restricting ovarian follicle expansion in patients with PCOS,to provide a theoretical basis for follicular dysplasia,ovulation disorders and other diseases caused by abnormal ovarian follicle expansion.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

Objective To investigate the underlying mechanism of Hongyu Decoction in the treatment of inflammatory bowel disease(IBD)based on serum amino acid metabolism.Methods A total of 50 male C57BL/6J mice were divided into control group,model group,sulfasalazine(SASP)group and Hongyu Decoction low-and high-dosage groups,with 10 mice in each group.Except for the control group,the rest groups were treated with 3%dextran sulfate sodium freely for seven consecutive days to establish the IBD model.The SASP group was given SASP solution at a dosage of 200 mg/kg by gavage,while the Hongyu Decoction low-and high-dosage groups were given Hongyu Decoction freeze-dried powder solution at dosages of 0.5 and 2.0 g/kg respectively by gavage for 11 consecutive days.The general condition was monitored and DAI score were calculated.After the mice were sacrificed,the length of colons was measured,ELISA was used to detect serum TNF-α,IL-1β,IL-17 contents,HE staining was used to observe the morphology of colon tissue,and Alizarin blue staining was used to evaluate the secretion of mucin levels by intestinal epithelial goblet cells,UPLC-MS and multivariate statistical methods were used to analyze the serum amino acid metabolism profiles of mice in the control group,model group and Hongyu Decoction high-dosage group,and differential amino acids were screened.Pathway enrichment analysis was performed on differential amino acids using MetaboAnalyst 5.0.Results Compared with the control group,the DAI score of the model group mice significantly increased(P<0.001),the colon length was significantly shortened(P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 significantly increased(P<0.001);with widespread ulceration of colon tissue,disappearance of mucosal epithelium and intestinal crypt structure,infiltration of lymphocytes and neutrophils,congestion and edema of intestinal mucosa,proliferation of submucosal connective tissue,reduced number of colonic goblet cells and mucin secretion.Compared with the model group,the Hongyu Decoction high-dosage group showed a significant decrease in DAI score(P<0.001),while the SASP group and the Hongyu Decoction low-and high-dosage groups showed a significant increase in colon length(P<0.05,P<0.001),and the serum contents of TNF-α,IL-1β and IL-17 were significantly reduced(P<0.001);the colonic villi were relatively intact,the glands were clear and arranged neatly,the branches of the intestinal crypts were obvious,no obvious edema was observed,and the number of colonic goblet cells and mucin secretion increased.Seven potential biomarkers for IBD in mice were identified through serum metabolomics screening,including tryptophan,serine,glutamate,valine,histidine,methionine and phenylalanine;two potential biomarkers for the treatment of IBD with Hongyu Decoction were identified,namely valine and tyrosine.The results of pathway enrichment analysis showed that the differential amino acids in the model group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,histidine metabolism,cysteine and methionine metabolism,phenylalanine metabolism and arginine biosynthesis;the differential amino acids in Hongyu Decoction high-dosage group mainly involved the biosynthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of alanine,aspartate and glutamate,and the biosynthesis of arginine.Conclusion Hongyu Decoction can improve intestinal epithelial damage and inflammatory cell infiltration in IBD mice,protect the integrity of the intestinal mucosal barrier,and may be related to regulating amino acid metabolism in the body.