Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

Objective To analyze the allocation and utilization efficiency of hospital beds from 2017-2021,and to provide a reference for the optimal allocation of hospital bed resources in Shenzhen.Methods Descriptive statistics method,bed efficiency index and bed utilization model were used to evaluate the hospital bed allocation and utilization efficiency of Shenzhen hospitals for 5 years.Results The number of beds in Shenzhen increased every year,with the highest growth rate of 21.54%,and the number of beds per 1000 resident population increased from 3.04 in 2017 to 3.25 in 2021.From the bed efficiency index,all three types of hospitals(general hospitals,specialized hospitals,traditional Chinese medicine hospitals)in Shenzhen are operating at low efficiency.Government-run hospitals are operating at high efficiency except for 2020,while socially-run hospitals are operating at low efficiency for five years,with bed efficiency indexs below 0.4.From the bed utilization model,Shenzhen general hospitals are turnover hospitals,Chinese medicine hospitals are bed-pressure hospitals for the first two years and then turn into efficiency hospitals,and specialty hospitals are idle hospitals.The government-run hospitals were efficient hospitals for 5 years,while the socially-run hospitals were idle hospitals for 5 years.Conclusion It is necessary to reasonably allocate health resources to increase the number of beds,improve the ability of hospitals to admit and absorb patients,and improve the operational efficiency of beds;the improvement and upgrading of beds in various types of hospitals should be tailored to local conditions to promote the realization of the continuity of care by integrating the concept of health care.

Objective To evaluate the efficacy of transurethral resection of bladder tumor(TURBT)in treating cystitis glandularis(CG),and to explore the influencing factors.Methods A retrospective analysis was conducted on 243 CG patients treated with TURBT during Jan.2013 and Dec.2020 in our hospitals.Postoperative efficacy was assessed using global response assessment(GRA).The correlation between GRA score and the demographic characteristics,comorbidities,initial complaints,and postoperative recurrence was determined with logistic regression analysis.Results Among the 243 patients,3.70％(9/243)had dysplasia,2.47％(6/243)had exuberant hyperplasia of Brinell's nest,and 2.06％(5/243)had intestinal metaplasia.The mean GRA score was(2.02±0.72)after a follow-up of(47.10±28.53)months.Re-operation was performed in 10.29％(25/243)of the patients due to recurrence,and the improvement of hydronephrosis and dysuria was 70.59％(12/17)and 50.00％(15/30),respectively.Pelvic fat increase developed in 1 patient(0.41％)after surgery.Logistic regression analysis showed that postoperative GRA score was not significantly correlated with demographic characteristics,body mass index,comorbidities,alcoholism and postoperative recurrence(P＞0.05).Conclusion TURBT is an effective method in the treatment of CG,which can significantly improve patients'hydronephrosis and dysuria.However,approximately 10％of the patients experience recurrence,necessitating further surgery,which suggests the need for vigilance regarding potential recurrence during treatment.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Objective:To investigate the safety and effectiveness of tension adjustment technique using anatomical landmarks during retropubic midurethral synthetic sling.Methods:The data of 36 consecutive female patients with urinary incontinence, who had underwent retropubic midurethral synthetic sling procedure from January to August 2019 were analyzed retrospectively. The mean age was (60.83±7.93) years old and the body mass index was (24.43±2.44) kg/m 2. Among the recruited subjects, 36 had positive stress test and Marshall-Marchetti test. 20 (55.6%) were pure stress urinary incontinence, and 16 (44.4%) were mixed urinary incontinence. The severity of incontinence was classified into mild (5 cases, 13.9%), moderate (14 cases, 38.9%), severe (13 cases, 36.1%) and very severe (4 cases, 11.1%) using one-hour pad tests. Urodynamics were performed in 17 cases, with 5 (29.4%) presented detrusor overactivity, 3 (17.7%) possessed intrinsic sphincter deficiency. For each case, the tension of the sling was adjusted based on the anatomical landmarks, i. e. using an angled clamp attached closely to the pubic symphysis ventrally and the tip parallel to the edge of hymen dorsally. All patients were catheter-free right after the procedure. The subjective and objective effectiveness, and safety (the rate of urinary retension after surgery and postvoid residual volume 3 months later) were evaluated.The subjective cure rate was was defined as complete leakage free or very mild leakage during excessive bladder filling and fierce cough. The subjective effectiveness was defined as over 50% improvement of the leakage symptom. The objective cure rate was defined as a negative stress test. Results:For all 36 patients, the median hospital stays was 8 (5-95)h. No bladder perforation or transfusion cases. All patients were catheter-free right after the procedure, with no incidence of urinary retention. 27 patients completed a 3-month follow-up, with 22 had post-void residual data, 23 had subjective effectiveness data and 23 had objective effectiveness data. The median post-void residual was 7.5 (5-64) ml, subjective cure rate was 91.3% (21/23), and objective cure rate was 95.7% (22/23). 8.7% (2/23) reported difficult urination alleviated without the necessity of clinical interference. No urethra erosion or vagina extrusion was found. At 2-year follow-up, 34 patients completed assessment by phone. The subjective cure rate was 91.2% (31/34), with only 2.9% (1/34) reported difficult urination. Besides, at 3-month follow-up, there was no difference regarding the subjective cure rate [100.0%(12/12) vs. 81.8%(9/11)]or objective cure rate [91.7%(11/12) vs. 100.0%(11/11)] between patients with stress and mixed incontinence. No difference was noted among patients with mild, moderate, severe and very severe leakage[75.0% (3/4) vs. 100.0%(6/6) vs. 90.0%(9/10) vs. 100.0%(3/3)]. Of the 12 cases with urodynamic records, the presence of detrusor overactivity [66.7%(2/3) vs. 88.9%(8/9)] or intrinsic sphincter deficiency [0(0/1) vs. 90.9%(10/11)] did not significantly affected the cure rate of the procedure. At 2-year follow-up, there was no difference regarding the subjective cure rate between patients with stress and mixed incontinence [94.7%(18/19) vs. 86.7%(13/15)]. No difference was also noted among patients with mild, moderate, severe and very severe leakage[80.0%(4/5) vs. 100.0%(13/13) vs. 83.3%(10/12) vs. 100.0%(4/4)]. Of the 16 cases with urodynamic records, the presence of detrusor overactivity [60.0%(3/5) vs. 90.9%(10/11)]or intrinsic sphincter deficiency [66.7%(2/3) vs. 84.6%(11/13)]did not significantly affected the cure rate of the procedure.Conclusions:Tension adjustment using anatomic landmarks during sling procedure is safe and feasible for urinary incontinence, with minimum complications and residual volume, and high subjective/objective cure rate.

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

O-GlcNAcylation is the addition of a single N-acetylglucosamine(GlcNAc)moiety to the hydroxyl groups of serine or threonine residues of nuclear and cytoplasmic proteins. The transcription factors, kinases of the metabolic pathways and some cytoplasmic enzymes can be O-GlcNAcylated to affect cell transcription, signal transduction, cell metabolism and other biological functions. Abnormal glucose metabolism of tumors has been a hotspot in the research field of tumor pathogenesis and therapeutic targets recently. O-GlcNAclation regulates the glucose metabolism of tumor by affecting the activity of kinases in the metabolic pathway, which is closely associated with the abnormal glucose metabolism of tumor. The abnormal O-GlcNAcylation is one of the potential reasons of cancer. In this review, in order to provide a theoretical reference for developing anti-tumor targets and drugs targeting O-GlcNAc modification, we briefly summarized how O-GlcNAcylation regulated glucose metabolism on glucose metabolism, glucose uptake, glycolysis, pentose phosphate pathway and tricarboxylic acid cycle in cancer cell.

Objective To evaluate the efficacy of modified abdominal laparoscopy in the repair of complex vesical vaginal fistula after total hysterectomy.Methods The clinical data of 58 cases of urinary bladder and vagina fistula in our hospital from April 2014 to December 2017 were retrospectively analyzed,of which 32 cases were repaired by ordinary abdominal laparoscopy from April 2014 to February 2016 and 26 cases were repaired by modified abdominal laparoscopy from March 2016 to June 2017.On the basis of the original laparoscopy,the modified transabdominal laparoscopy enlarged the free range between the vaginal stump and the bladder,separated the anterior vaginal wall from the bladder completely and dissociated the retrovaginal peritoneum,wrapping around the vaginal stump to make the peritoneum.The median age of ordinary group was 52 (range:33-67)years old,the median course of disease was 12 (range:3-40) months,and the size of fistula was (25.5 ± 10.3) mm.The median age of modified group was 50 (range:37-65) years,the median course of disease was 11.5 (range:3-36) months,and the size of the fistula was (26.3 ± 9.1) mm.The operation time,bleeding volume,the time of hospitalization,the rate of complications and the success rate of the operation were compared.Results The operation time of the two groups was successfully completed.The operation time of the modified group [(164.2 ± 21.2) min] was significantly shorter than that of the common group [(201.4 ± 25.8) min],and the difference was statistically significant (P ＜ 0.01).In the modified group,the cure rate (100.0％,26/26) was higher than that in the normal group (84.4％,27/32,P ＜ 0.05).There was no significant difference in the amount of intraoperative bleeding[50 (10-100) ml vs.55 (5-110) ml],hospitalization time [(9.1 ± 1.7) d vs.(10.0 ± 1.8) d],postoperative infection [19.2％ (5/26) vs.15.6％ (5/32)],urinary incontinence [7.7％ (2/26) vs.9.4％ (3/32)],urinary frequency [15.4％ (4/26) vs.21.9％ (7/32)],intestinal obstruction [3.8％ (1/26) vs.9.4％ (3/32)] between the modified group and common group (P ＞ 0.05).Conclusions The modified transabdominal laparoscopic mode shortens the operation time,and improves the cure rate of the operation.Satisfactory results are recommended for the repair of high complex bladder vagina fistula.

Objective To analyze the activity of diadenylate cyclase ( DAC) encoded by LA3304 gene of Leptospira interrogans ( L. interrogans) and to investigate the influence of CdaR encoded by LA3303 gene on DAC activity. Methods The LA3304 gene in L. interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai was amplified by PCR and inserted into a prokaryotic expression system for expressing DAC. The expressed recombinant protein, rDAC, was purified by Ni-NTA affinity chromatography. High Perform-ance Liquid Chromatography ( HPLC) was used to measure the synthesis of c-di-AMP from ATP by rDAC in vitro. Bacterial two-hybrid analysis was used to detect the interaction between CdaR and DAC. Prokaryotic co-expression system was constructed and used in combination with HPLC to analyze the role of CdaR in acti-vating DAC. Results The constructed prokaryotic expression system for LA3304 gene of L. interrogans strain Lai could highly express the rDAC upon the induction of IPTG. The purified rDAC showed high purity with a single protein band in gel as indicated by SDS-PAGE. rDAC could synthesize c-di-AMP from ATP in vitro. CdaR interacted with DAC and enhanced the activity of DAC (P<0. 05). Conclusion DAC encoded by LA3304 gene was a diadenylate cyclase that could convert ATP into c-di-AMP. CdaR promoted the acti-vation of DAC and formed a CdaR-DAC system with DAC. The system was involved in the synthesis of c-di-AMP in L. interrogans.

Objective To understand and determine the biological activity and pathogenicity of metalloendopeptidases encoded by LA2582 and LA2901 genes of Leptospira interrogans(L.interrogans) sero-group Icterohaemorrhagiaeserovar Lai strain Lai. Methods Structures and functions of LA2582 and LA2901 genes were analyzed by using bioinformatic software. Prokaryotic expression systems for expressing the extra-cellular regions of LA2582 and LA2901 genes were generated. The target recombinant expression products, rLA2582 and rLA2901,were extracted by Ni-NTA affinity chromatography. The Azo-casein-hydrolyzingactiv-ity of rLA2582 and rLA2901 was detected by spectrophotometry. Activities of rLA2582 and rLA2901 in the hydrolysis of Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans, a fluorescence-labeling pentapeptide substrate, were de-tected by fluorospectrophotometry,and then the Km and Kcat values were determined. SDS-PAGE and spec-trophotometry were performed to detect the activities of rLA2582 and rLA2901 in hydrolyzing extracellular matrix molecules such as collagen type-Ⅰ (COL1), fibronectin (FN) and Congo red-labeling elastin (ELN). Real-time fluorescent quantitative RT-PCR(qRT-PCR) and Western blot were respectively used to measure the expression of LA2582 and LA2901 genes at mRNA and protein levels after infecting human um-bilical vein endothelial cells(HUVEC) with L. interrogans strain Lai. Results The gene products of LA2582 and LA2901 genes were identified as the signal peptide and matrix metalloproteinase motif HXH-containing Zn2+-dependent Gly-Gly metalloendopeptidases belonging to the M23 superfamily. rLA2582 and rLA2901 did not hydrolyze Azo-casein (Km=126.54 μmol/L, Kcat=4.67/s), but could hydrolyze the pentapeptide substrate (Km=190. 25 μmol/L, Kcat 4. 86/s). rLA2582 and rLA2901 could hydrolyze COL1, FN and ELN. Expression of LA2582 and LA2901 genes at both mRNA and protein levels was signifi-cantly increased after infection of HUVEC with L.interrogans strain Lai(P<0.05). Conclusion The prod-ucts of LA2582 and LA2901 genes of L.interrogans strain Lai are Zn2+-dependent M23 metalloendopeptidas-es, which can hydrolyze multiple ECM molecules and are closely associated with the leptospiral invasiveness.