Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer，but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW)，MR-Egger，weighted median，maximum likelihood，robust adjustment feature score and MR-PRESSO，with IVW as the primary analysis method.Additionally，sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR：1.42)，Desulfovibrionales (Order) (OR：1.48)，Eubacterium ruminantium group (OR：1.33)，Olsenella (OR：1.24)，Ruminococcaceae UCG002 (OR：1.39)，Ruminococcaceae UCG005 (OR：1.42) and Ruminococcaceae UCG013 (OR：1.64) significantly increased the risk of bladder cancer.Conversely，Bacteroidetes (Phylum) (OR：0.61)，Eubacterium brachy group (OR：0.80)，Ruminococcaceae UCG004 (OR：0.73)，Rikenellaceae (Family) (OR：0.67)，Lachnospiraceae ND3007 group (OR：0.47), Adlercreutzia (OR：0.73) and an unknow genus (OR：0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer，among which Lachnospiraceae UCG004，Desulfovibrionales (Order)，Eubacterium ruminantium group，Olsenella，Ruminococcaceae UCG002，Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer，while Bacteroidetes (Phylum)，Eubacterium brachy group，Ruminococcaceae UCG004，Rikenellaceae (Family)，Lachnospiraceae ND3007 group，Adlercreutzia and an unknown genus are the protective factors.

In order to further standardize the diagnosis and treatment of atopic dermatitis by health-care professionals, as well as to enhance the awareness of atopic dermatitis among patients and promote doctor-patient communication, Chinese Society of Dermatology and China Dermatologist Association jointly initiated the development of guidelines on the diagnosis and treatment of atopic dermatitis (specialist version, general practitioner version and patient version). The development working group had planned the development process of the 3 versions of guidelines with reference to relevant development manuals and methodological articles. It is also intended to expound the details of registration, working group establishment, clinical question collection, evidence search and grading, recommendation formation and consensus through this protocol, aiming to enhance the transparency of guideline development.

Pregnancy ; Female ; Humans ; Placenta Accreta/surgery* ; Cesarean Section ; Retrospective Studies ; Biomarkers ; Hysterectomy ; Placenta Previa ; Placenta

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.

Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.

OBJECTIVE：To investigate the “dose-effect-toxicity”correlation of Miao medicine Wikstroemia indica before and after processed on anti-immnue inflammation of mice . METHODS ：Mice were divided into blank group ，model group ，ethanol extract of W. indica raw product groups 1-6，ethanol extract of W. indica processed product by “sweat soaking method ”groups 1-6 （hereinafter called “raw groups 1-6”“processed groups 1-6”for short ，drug dosage were 0.13，0.20，0.26，0.52，1.04，2.6 g/kg）， positive group （cyclophosphamide，36.4 mg/kg），with 10 mice in each group. Except for blank group ，other groups were given 1％ 2，4-dinitrofluorobenzene-acetone-sesame oil mixed solution to induce delayed type hypersensitivity model. After modeling， blank group and model group were given constant volume of 1.0％ CMC-Na solution intragastrically ，and administration groups were given relevant medicine 20 mL/kg intrag astrically，oncea day ，for consecutive 5 d. A fter last medication ，ear swelling degree of mice were recorded ；the inhibition rate of swelling degree， half effective dose （ED50） and 95％ confidence 158-02-32）； interval（CI）of raw and processed products were calculated ； the weight of heart ，liver，spleen，lung and kidney were measured and the indexes of organs were calculated ；ELISA 1161472062@qq.com and modified chemical oxidation method were used to determine the serum levels of inflammatory factors （TNF-α， IL-10） and liver and renal function indexes （ALT，AST， TBIL，BUN，CREA）. RESULTS：Compared with blank group ，the degree of ear swelling in the model group was significantly increased（P＜0.05）. Compared with model group ，ear swelling degree of mice were decreased significantly in different doses groups of ethanol extract of raw and processed products of W. indica （P＜0.05）. The inhibition rate of swelling increased with the increase of dose ，ED50 and 95％CI of delayed hypersensitivity ear swelling were 0.239 6（0.129 0，0.445 2）g/kg and 0.147 3（0.076 8，0.282 7）g/kg，respectively. Compared with blank group ，liver index and serum TNF-α level of mice were increased significantly in model group ，while lung index and serum IL- 10 level were decreased significantly （P＜0.05）. Compared with model group ，the levels of liver indexes （positive group ，raw group 3，processed groups 1-6）and serum TNF-α levels（positive group ，raw groups 1-3，processed groups 1-4） were decreased significantly in different administration groups ；while the levels of lung indexes （positive group ，raw groups 3-6 and processed groups 3-6），serum IL- 10 levels（raw groups 1，2，4 and 5，processed groups 2-6），ALT，AST，BUN and CREA levels （raw groups 4-6），TBIL levels （raw groups 3-6 ）were increased significantly （P＜ 0.05）. CONCLUSIONS ：The ethanol extract of raw product of W. indica has certain anti-inflammatory activity ，and has certain hepatorenal toxicity to mice ，with certain “dose-effect-toxity”correlation. The ethanol ectract of processed product of W. indica has certain anti-inflammatory activity too ，but its hepatorenal toxicity was lower than raw product. The “sweat soaking method ” possesses the function of “retaining efficiency and reducing toxicity ”for processing W. indica .

OBJECTIVE：To compare the content changes of active/toxic ingredient genkwanin in ethanol extract from Wikstroemia indica before and after processing with “sweat soaking method ”and the effects of processing method on its anti-oxidation ability. METHODS ：HPLC method was adopted to determine the content of genkwanin in W. indica before and after processing with “sweat soaking method ”. The separation was performed on Diamonsil C 18 column with 0.2％ phosphoric acid solution-methanol as mobile phase （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃ and detection wavelength was set at 346 nm. The sample size was 20 µL. SD rats were randomly divided into blank group ，W. indica raw product ethanol extract group （317.52 mg/kg，called“raw-product group ”as short ）and W. indica processed product ethanol extract group （317.52 mg/kg，called“processed-product group ”as short ），with 6 rats in each group. Blank group was given constant volume of 1.0％CMC-Na solution intragastrically ，and administration groups were given relevant medicine suspension intragastrically；all of them were given 20 mL/kg，once a day ，for consecutive 14 days. The contents of serum oxidant stress indexes（MDA，CAT，SOD）in rats were determined by ELISA. RESULTS ：The linear range of genkwanin were 0.147-27.360 μg （r＝0.999 9）；RSDs of precision ，reproducibility and stability tests were all lower than 3％ ；average recoveries were 98.64％-98.92％（RSD＜1％，n＝3）. Before and after processing with “sweat soaking method ”，average contents of genkwanin in W. indica were 0.377 6 and 0.234 0 mg/g. Compared with blank group ，the serum content of SOD in raw-product group was increased significantly ，while CAT content was decreased significantly （P＜0.05 or P＜0.01）；the serum content of MDA was decreased significantly in processed-product group ，while SOD content was increased significantly （P＜0.05 or P＜0.01）. MDA content of processed-product group was significantly lower than that of raw-product group ，while SOD content was significantly higher than raw-product group （P＜0.05）. CONCLUSIONS ：After proce ssing with “sweat soaking method ”，the content of genkwanin in W. indica is decreased ，and antioxidant activity is increased .“Sweat soaking method ”processes certain function of “reducing toxicity and increasing efficiency ”.

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.