Objective To observe the expression and trends of tight junction proteins Occludin and zonula occlu-den-1(ZO-1)in blood-brain barrier(BBB)of rats with traumatic brain injury(TBI),and to explore the interven-tion effect of cannabidiol(CBD)on the BBB.Methods The TBI model of rat was prepared by modified"Feeney free fall method"and randomly divided into three groups:the sham-operated group(Sham group),the model group(TBI+vehicle group)and the CBD intervention group(TBI+CBD group),with 24 rats in each group.Each group was subdivided into six time points:8 h,1,2,3,5 and 7 d after injury.The expression of Occludin and ZO-1,which are closely related to the permeability of BBB,was detected by immunohistochemistry,immuno-fluorescence staining and Western blot at different points.The permeability of BBB was detected by sodium fluores-cein assay.Results The results of immunohistochemistry showed that compared with Sham group,the positive ex-pression of Occludin and ZO-1 decreased with time after brain trauma(P<0.05),and both reached the lowest level at 2 d.The expression levels of Occludin and ZO-1 were up-regulated after 1 d of CBD intervention(P<0.05).Immunofluorescence staining showed a similar trend to Western blot results,with Occludin and ZO-1 fluo-rescence expression intensity and protein expression reduced after TBI compared with Sham group(P<0.05).And the expression levels of Occludin and ZO-1 were up-regulated after 2 d of CBD intervention(P<0.05).The results of fluorescein sodium experiment showed that the BBB integrity of brain tissue was destroyed after TBI,and the permeability increased after TBI(P<0.01).The permeability of BBB decreased after CBD intervention(P<0.05).Conclusion The expression of tight junction proteins Occludin and ZO-1 decreases after TBI,and the permeability of BBB is disrupted,and CBD intervention reverses the disruption of the BBB by TBI.

Objective To investigate testicular damage in traumatic brain injury(TBI)rats and to analyze the in-terventional effects of cannabidiol(CBD)on TBI-induced testicular damage.Methods 18 Sprague Dawley(SD)rats were randomly divided into three groups:the sham operation group(Sham group),model group(TBI group)and treatment group(TBI+CBD group).HE staining was used to observe the testicular histopathological changes in the rat testis.ELISA was used to detect testosterone level in rat serum.TUNEL staining was utilized to observe apoptosis,while immunofluorescence staining,Western blot and RT-qPCR were employed to evaluate Bax,Bcl-2,Cleaved Caspase-3 and TNF-α protein and mRNA expression.Results HE staining showed pathological changes in the testes of TBI rats compared with those in the Sham group.ELISA assay showed a decrease in testosterone levels in the TBI group compared to the Sham group,but there was no significant difference(P＞0.05).Immunofluores-cence results showed that the intensity of Bax fluorescence expression increased in the TBI group compared with the Sham group(P＜0.01),whereas the intensity of Bax fluorescence decreased and the intensity of Bcl-2 fluorescence increased in the rats after the CBD intervention(P＜0.01).Western Blot results showed that CBD treatment in rats decreased the protein levels of testicular apoptosis-related proteins(Bax and Cleaved Caspase-3,all P＜0.05)and inflammation-related proteins(TNF-α,P＜0.01),and increased the protein level of the anti-apoptotic protein,Bcl-2(P＜0.05).The trend of RT-qPCR results was similar,with mRNA expression of Bax(P＜0.05)and TNF-α(P＜0.01)decreased and mRNA expression of Bcl-2 increased after CBD intervention compared with the TBI group(P＜0.05).Conclusion TBI induces testis injury,and CBD treatment effectively repairs apoptosis and in-flammatory in testicular tissue of TBI rats.

Objective To explore the therapeutic effect of transumbilical single-port laparoscopic high uterosacral ligament suspension(HUS)and iliacpubic ligament fixation(ILF)in the treatment of pelvic organ prolapse(POP)mainly caused by middle pelvic defects.Methods Clinical data of 15 cases of POP with middle pelvic defects from June 2017 to June 2023 were analyzed retrospectively.The HUS and ILF were performed by transumbilical single-port laparoscopy.At one year after operation,gynecological examination(POP-Q system)and maximum straining pelvic MRI examination were performed for objective evaluation.The Pelvic Floor Distress Inventory Short Form(PFDI-20)and Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire(PISQ-12)were used for subjectiveevaluation.Results Theoperationtimewas 65-135 min(mean,102.9±16.3 min),thebleedingvolumewas 20-50 ml,and the postoperative hospital stay was 6-9 d.Follow-up time ranged from 6 to 72 months(mean,42.8±22.3 months),among which 14 cases were≥12 months.No pelvic pain,lumbosacral pain,urinary retention and thread exposure occurred.Stress urinary incontinence(SUI)occurred in 1 case at 1 year after operation.Surgical failure was noted in 1 case(degree Ⅱ),the objective success rate being 93.3%(14/15).At 1 year after operation,the distance from the anatomical landmarks of pelvic MRI to the pubococcygeal line(PCL)was significantly higher than that before operation(P<0.01),and the PFDI-20 and PISQ-12 scores were significantly better than those before operation(P<0.01).Conclusions Transumbilical single-port laparoscopic HUS and ILF is a safe and effective mutual aid procedure for the treatment of POP mainly caused by middle pelvic defects with surgical indications,which can improve pelvic floor function and quality of life.It is simple and easy to perform with low cost of consumables,which is suitable for primary hospitals.

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.
Stenotrophomonas/genetics* ; Drug Resistance, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Genomics ; Microbial Sensitivity Tests

Objective : To observe the expression of glial fibrillary acidic protein (GFAP) in the brain tissue of rats with traumatic brain injury (TBI) and the differential changes between brain regions. Methods : The TBI model of rats was prepared by the modified Feeney free fall method , and it was randomly divided into the sham⁃operated qPCR were used to observe the morphological changes of activated astrocytes and the expression of GFAP in different brain regions after TBI. Results : Immunohistochemical staining showed that astrocytes were activated in all brain regions on the right side of TBI , and the only brain regions that spilled over to the contralateral side ( left) were cortical region 1 and midbrain regions. RT⁃qPCR results showed that GFAP mRNA was highly expressed in all brain regions on the right side of TBI , affecting the contralateral cortex and midbrain regions. Western blot results showed that GFAP protein was highly expressed in all brain regions on the right side of TBI , and it spread to the contralateral midbrain regions. Conclusion TBI can cause the activation of astrocytes and increase GFAP expression in the right brain regions , while also affecting the contralateral (left) cortex 1 and midbrain regions.

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

The mucosal surfaces of the human body are typically colonized by polymicrobial communities, they exist in the gastrointestinal tract, skin, oral cavity, and genitourinary tract, as well as in anatomical sites previously considered sterile, including the lung. These communities interact with the mucosal immune system to maintain homeostasis in health, emphasizing the important role of " second genome" , which is very important to human health. The human lower respiratory tract also harbor many microbes, the imbalance of microbiome composition maybe critically related with many lung disease. Up to date, researches on microbiome of lung caner is still on the first step. Our review mainly describes the characteristic composition of lung microbiome, and the relationship with diseases, especially with lung cancer. We attempts to provide the basis information for further researches about the relationship between human lung microbiome and lung cancer.

Objective:To investigate the expressions and correlation of bcl-2, programmed death-1 (PD-1) and programmed death ligand-1(PD-L1) in diffuse large B-cell lymphoma (DLBCL) tissue specimens, and the relationship between chemotherapy efficacy and prognosis of DLBCL patients.Methods:The expressions of bcl-2, PD-1 and PD-L1 in 82 patients with DLBCL who were admitted to Chenzhou First People's Hospital of Hunan Province from May 2011 to April 2014 were detected by using immunohistochemistry, and the correlation of the expressions of bcl-2, PD-1 and PD-L1 with clinicopathological characteristics and prognosis was analyzed.Results:The positive rate of bcl-2, PD-L1 and PD-1 in cancer tissues of DLBCL patients was 53.7% (44/82), 56.1% (46/82) and 32.9% (27/82), respectively. There was a correlation between bcl-2 and PD-L1 expression ( r = 0.306, P = 0.005). Bcl-2 was highly expressed in patients with international prognosis index (IPI) score 3-4 points, non-germinal center B-cell-like (non-GCB) subtype and B symptoms (all P < 0.05); PD-1 was highly expressed in patients with IPI score 3-4 points ( P < 0.05); PD-L1 was highly expressed in patients with IPI score 3-4 points, tumor stage Ⅲ-Ⅳ, B symptoms, ≥60 years old, and non-GCB (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in bcl-2-negative group were better than those in the bcl-2-positive group, and the differences were statistically significant (both P < 0.05); OS and PFS in PD-L1-negative group were better than those in PD-L1-positive group, and the differences were statistically significant(both P < 0.01). There were no statistical differences in OS and PFS between PD-1-positive group and PD-1-negative group (both P > 0.05). OS and PFS in bcl-2 and PD-L1 co-expression group were worse than those in both negative or any negative group (all P < 0.01), and PFS in bcl-2 and PD-1 co-expression group was worse than those in both negative or any negative group ( P = 0.044). Cox multivariate analysis showed IPI score 3-4 points and B symptoms were the independent influencing factors of OS in DLBCL patients (both P < 0.01); IPI score 3-4 points, B symptoms and PD-L1-positive were the independent influencing factors of poor PFS in DLBCL patients (all P < 0.05). Conclusion:The positive expressions of bcl-2 and PD-L1 are the independent factors for the poor prognosis of DLBCL patients, which may become new targets for the treatment of DLBCL.