ObjectiveTo screen optimized protocol of acupuncture for post-prostatectomy urinary incontinence （PPUI） patients， and to provide evidence for clinical practice. MethodsMEDLINE， Embase， Cochrane Library， Web of Science， Chinese Biomedical Literature Database， China National Knowledge Infrastructure， WanFang and VIP databases were searched to collect randomized controlled trials of acupuncture for PPUI. The search was conducted from the establishment of the database to February 1， 2024， and the quality of the literature was evaluated to exclude the studies with a high risk of overall bias or modified Jadad ＜3， and constructed acupuncture protocol and performed meta-analysis. We used International Consultation on Urinary Incontinence Short Form （ICI-Q-SF） scores， quality of life scores， overall effective rate， and modified Jadad scores as beneficial indicators， and the number of acupoints selected， stimulation duration， the number of acupuncture， and the duration of the treatment course as costly indicators， to derive the standardized protocol matrix， and used the entropy method to determine the weights of the different decision-making indicators， and finally combined with the Technique for Order Preference by Similarity to Ideal Solution （TOPSIS） for comprehensive evaluation. ResultsNine studies met the criteria， and the acupuncture treatments involved were constructed as six protocols including electrical acupoint stimulation with low-frequency， electroacupuncture at four acupoints of sacral region， replenishing qi and tonifying kidney acupuncture， body acupuncture plus pelvic floor muscle training， auricular acupuncture， and electroacupuncture plus pelvic floor muscle training. The ICI-Q-SF， number of acupuncture sessions， and total effectiveness rate were given higher weights in the decision-making indexes， while the stimulation duration and the duration of treatment course were given lower weights； the entropy method of TOPSIS was used for the evaluation and proved that the best protocol was the electroacupuncture at four acupoints of sacral region which used continuous-wave electroacupuncture with a frequency of 2 Hz for 60 min each time， and required the needle sensation to radiate to the root of the penis， with the advantages of streamlined selection of acupoints， a significant reduction in ICI-Q-SF， and an increase in the effectiveness rate. ConclusionThe final optimized protocol was electroacupuncture at four acupoints of sacral region， which can provide an evidence-based basis for clinical decision-making and guideline development.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P＜0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P＜0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P＜0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

OBJECTIVE: To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1). METHODS: Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC₅₀) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay. RESULTS: The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC₅₀ of CA46-C23-KD cells to adriamycin was (0.147±0.02) μg/ml, which was significantly lower than (0.301±0.04) μg/ml of CA46-C23-KNC cells and (0.338±0.05) μg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G₂/M phase also decreased, while G0/G1 phase increased in cell cycle. CONCLUSION The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.
Humans ; Leukocytes, Mononuclear/metabolism* ; Apoptosis ; Cell Line, Tumor ; Lymphoma ; Thymidine Kinase/pharmacology* ; Doxorubicin/pharmacology* ; Cell Division ; RNA, Messenger/genetics*

OBJECTIVES: To study the influence of family structure on depression and anxiety symptoms in adolescents and its mechanism. METHODS: The cluster sampling method was used to select the students from seven middle schools in Shanghai, China. An online questionnaire survey was conducted using a self-made general status questionnaire, Childhood Trauma Questionnaire, Children's Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The methods including one-way analysis of variance, chi-square test, binary logistic regression analysis, and mediating effect analysis were used to evaluate depression and anxiety symptoms in adolescents and the difference in childhood trauma and its mediating effect. RESULTS: Compared with the adolescents from nuclear families, the adolescents from three-generation lineal families had a lower risk of depression symptoms (OR=0.794, 95%CI: 0.649-0.972, P<0.05), while those from host families had a higher risk of depression symptoms (OR=4.548, 95%CI: 1.113-18.580, P<0.05). The adolescents from inter-generational families and host families had a significantly higher score on the Childhood Trauma Questionnaire subscale of emotional neglect (P<0.05). Emotional neglect played a mediating role in the influence of inter-generational families and host families on depression symptoms in adolescents. CONCLUSIONS Parents and grandparents have a certain positive effect in family structures. Separation from parents may make adolescents perceive more emotional neglect, which may increase the occurrence of depression symptoms.
Child ; Humans ; Adolescent ; Depression/epidemiology* ; Family Structure ; Child Abuse/psychology* ; China ; Anxiety/epidemiology* ; Surveys and Questionnaires

OBJECTIVES: To investigate the association between maternal job burnout and adolescent depression and the mediating effect of maternal depression and parenting style. METHODS: A cross-sectional study was conducted. The cluster random sampling method was used to select 2 572 adolescents from 7 middle schools in Shanghai, China, from April to May, 2021. A survey was performed for these adolescents and their mothers. The research tools included a general information questionnaire, Maslach Burnout Inventory-General Survey, Center for Epidemiologic Studies Depression Scale, short-form of Egna Minnen av Barndoms Uppfostran, and Children's Depression Inventory. A structural equation model was established, and the Bootstrap method was used to investigate the mediating effect. RESULTS: The detection rate of depressive symptoms was 12.71% (327/2 572) among the adolescents. The scores of maternal job burnout, maternal depression, and negative parenting style were positively correlated with the score of adolescent depression (P<0.05), and the score of positive parenting style was negatively correlated with the score of adolescent depression (P<0.05). Maternal depression and parenting style played a mediating role between maternal job burnout and adolescent depression, including the individual mediating effect of maternal depression, the individual mediating effect of positive parenting style, and the chain mediating effect of maternal depression-negative/positive parenting style. CONCLUSIONS Maternal job burnout may affect adolescent depression through the mediating effect of depression, parenting style, and depression-parenting style, suggesting that the symptoms of adolescent depression can be reduced by alleviating maternal job burnout, improving maternal depression, increasing positive parenting behaviors, and reducing negative parenting behaviors.
Child ; Adolescent ; Humans ; Cross-Sectional Studies ; Depression/etiology* ; Parenting ; China ; Burnout, Psychological

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.
Female ; Humans ; Middle Aged ; Class I Phosphatidylinositol 3-Kinases/metabolism* ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis* ; DNA Mismatch Repair/genetics* ; Endometrial Neoplasms/pathology* ; Microsatellite Instability ; Mismatch Repair Endonuclease PMS2/genetics* ; Molecular Typing

Aim To study the regulation and mechanism of phloroglucinol in bladder smooth muscle spasm. Methods In vitro the experiment used bladder muscle strip to verify the relieving effect of phloro-glucinol on bladder spasm by different drugs. At the same time,RT-qPCR and Western blot were used to detect the expression levels of genes involved in the calcium signaling pathway caused by the antispasmodic effect of phloroglucinol. Results Phloroglucinol could relieve bladder spasm, and the antispasmodic effect was enhanced with the increase of concentration, and the expression of calponin 1 and MYLK3 in tissue cells increased. The results of RT-qPCR showed that the expression of Gprc5b G,Ppp2r5a, Chptl, Prkar2b ,Abcd2 and Rasdl genes in mouse bladder tissue significantly decreased, which was consistent with the sequencing results of RNA-seq.Conclusions Phloroglucinol can relieve bladder smooth muscle spasm, and its mechanism is related to calcium signaling pathway. Meanwhile, phloroglucinol also inhibits the expression of Rasdl gene, suggesting that it may be related to cell cycle , protein phosphorylation, choline metabolism, ATP synthesis and tumor-related pathways.