Type Ⅵ secretion system(T6SS)is a lethal weapon that releases effectors in direct contact to kill eukaryotic predators or prokaryotic competitors.T6SS is of great significance in bacterial environmental adaptability,pathogenicity,and gene horizontal transfer.T6SS has been identified in about 25％of Gram-negative bacteria.Because of its widespread existence,T6SS is considered the key factor of ecological competition.T6SS effectors exerting biological functions have high diversity and do not have conserved sequences,and the regulatory mechanisms involved are complex.Therefore,it is a hot and difficult topic in T6SS research.Vibrio fluvialis(V.fluvialis)as a newly emerging foodborne pathogen,has unique characteristics in the quantity,composition,and physiological function of T6SS,which is related to its wide environmental adaptability and pathoge-nicity.This article mainly reviews the research progress of V.fluvialis T6SS,including its composition,structure,functional activity,and regulatory mechanism.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To investigate the clinical characteristics,coexisting gene mutations and prognosis of acute myeloid leukemia(AML)patients with GATA2 gene mutation.Methods:The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively,the next-generation sequencing technology was used to detect the mutated genes in those patients.The clinical characteristics of AML patients with GATA2 mutations,the co-mutated genes of GATA2 mutations,and the effect of GATA2 mutation on prognosis were analyzed.Results:A total of 23 patients(6.2％)with GATA2 mutation was detected in 370 AML patients.Compared with GATA2 non-mutation group,patients in GATA2 mutation group were mostly normal karyotypes(P=0.037)and in low-risk cytogenetic stratification(P=0.028).The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group(P=0.010,P=0.009).There were no statistically significant differences between the two groups in terms of sex,age,white blood cell count(WBC),platelet count,hemoglobin,bone marrow(BM)blast,induction chemotherapy regimen and CR rate(P＞0.05).Among the 23 patients with GATA2 mutation,the most common co-mutated genes were CEBPAdm,NRAS(both 39.1％),NPM1,FLT3,TET2,WT1(all 17.4％),ASXL1 and IDH1(both 13.0％).Survival analysis showed that there was no statistical difference in 5-year overall survival(OS)and leukemia-free survival(LFS)rates between patients with and without GATA2 mutations in whole cohort(n=370)(P=0.306,P=0.308).Among 306 patients without CEBPAdm,the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group,but the difference was not statistically significant(P=0.092,P=0.056).Among 64 patients with CEBPAdm,there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group(P=0.104),but the 5-year LFS rate of the GATA2 mutation group was significantly decreased(P=0.047).Among the 23 patients with GATA2 mutation,16 cases received the"3+7"induction regimen,of which 12 cases received allogeneic hematopoietic stem cell transplantation(allo-HSCT);7 cases received the"DCAG"induction regimen,of which 3 cases received allo-HSCT.The CR rate was not statistically different between the"3+7"regimen group and the"DCAG"regimen group(P=1.000).The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group(P=0.021,P=0.020).Conclusion:GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification,and it is significantly associated with CEBPAdm and NRAS co-mutations.The prognostic significance of GATA2 is influenced by CEBPAdm.The choice of"3+7"or"DCAG"induction regimen in patients with GATA2 mutation does not affect their CR rate,while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Objective To investigate the feasibility of retroperitoneoscopy in the treatment of adrenal masses in infants under 6 months old.Methods From January 2020 to November 2023,retroperitoneoscopic surgery was performed in 5 infants under 6 months old with adrenal tumors.Their age was from 1 month and 18 days to 4 months and 27 days,and their body weight was 5-8 kg.The lesion was found by prenatal ultrasonography in 1 case and by abdominal ultrasonography for other reasons after birth in 4 cases.Ultrasound and CT indicated a diameter of 1.7-5.5 cm for the adrenal masses.Results The operations of adrenalectomy and tumor resection were completed under retroperitoneoscopy.The operative time was 65-135 min(median,94 min).The intraoperative blood loss was less than 10 ml.The postoperative drainage tube retention time was 3-6 d(median,5 d).Pathological diagnosis showed 4 cases of adrenal neuroblastoma and 1 case of adrenal hyperplasia.Follow-ups for 1-36 months(median,3 months)with abdominal ultrasound and CT scanning showed no recurrence or metastasis.Conclusion Retroperitoneoscopy is relatively safe for the treatment of adrenal tumors in infants under 6 months old(tumors with acceptable boundaries).

Objective To summarize the clinical experience of thoracoscopic treatment of anterior mediastinal enterogenous cysts.Methods From July 2019 to July 2023,27 children diagnosed as having anterior mediastinal enterogenous cysts were treated with total thoracoscopic surgery through the lateral thoracic approach(three port method)in our department.The patients were placed in a healthy lateral position.The observation hole was located in the 5th intercostal space under the scapula,and the other 2 operating holes were established based on the location of the lesion and the endoscopic diamond-shaped method,both of which were 5 mm trocars.The CO2 pneumothorax was established at a pressure of 6 mm Hg.The visceral pleura of the cyst was opened with an electric hook,the cyst was fixed and pulled by intestinal forceps,and the cyst was completely removed by forceps and electric hook separation alternately.Results No conversion to thoracotomy was required.Complete resection was performed in 26 cases,and residual cyst wall existed in 1 case.Esophageal muscular layer was opened in 9 cases.During the operation,cysts obstructed the surgical field of view in 5 cases,which was not conducive to observation.The cyst puncture and fluid extraction were performed.The operation time was 45-120 min(median,70 min).The amount of blood loss was 3-10 ml(median,5 ml).Postoperative hospitalization lasted for 2-5 d(median,3d).The 27 cases were followed up for 1-43 months(median,22 months),and there was no recurrence.The compressed trachea in 2 cases was all recovered,with emphysema fully recovered.Conclusions Thoracoscopic treatment of anterior mediastinal enterogenous cysts in children is safe and feasible.When the surrounding structure of the lesion is complex,it can be combined with bronchoscopic or gastroscopic surgery if necessary.

Objective:To analyze the characteristics of peripheral blood lymphocyte subsets in patients with relapsed neuromyelitis optica spectrum disorder (NMOSD) during rituximab (RTX) treatment and to clarify the influence of these lymphocyte subsets in NMOSD relapse.Methods:The monitoring data of lymphocyte subsets (175 times) in 76 patients diagnosed as having aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive NMOSD during RTX treatment at Department of Neurology, General Hospital of Chinese People's Liberation Army from August 2018 to August 2023 were collected. A relapse group ( n=26) and a non-relapse group ( n=149) were divided based on states at data collection (relapse or not). Two-sample t-test or Mann-Whitney U test were used to compare the differences in RTX administration intervals and lymphocyte subsets between the 2 groups. Additionally, a point biserial correlation analysis was performed to investigate the correlations of lymphocyte subsets and RTX administration intervals with NMOSD relapse. Results:The relapse group had significantly longer RTX administration intervals (10.00 [6.73, 14.37] months vs. 7.27[6.30, 9.10] months), statistically lower percentage of CD3 -CD56 + natural killer lymphocytes (10.72% [7.06%, 15.34%) vs. 13.85% [9.42%, 20.13%]), and significantly higher CD19 + B lymphocytes (7.41% [1.18%, 15.70%] vs. 3.55% [0.38%, 8.74%]) than the non-relapse group ( P<0.05). Positive correlations were noted between RTX administration intervals and NMOSD relapse and between CD3 -D19 +B lymphocytes and NMOSD relapse ( r=0.363, P<0.001; r=0.218, P=0.004); negative correlation was noted between CD3 -CD56 + NK lymphocytes and NMOSD relapse ( r=-0.193, P=0.011). Conclusion:Extended RTX administration interval can increase NMOSD relapse; CD3 -CD56 + natural killer lymphocytes and CD19 +B lymphocytes may regulate the disease states of NMOSD patients.

Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Fatal familial insomnia,an autosomal dominant prion disease,is rare.We reported the clin-ical symptoms,examination results,diagnosis,treatment,and prognosis of a patient who was diagnosed with fatal familial insomnia.Furthermore,we described the unique clinical manifestations that involuntary movements and laryngeal stridor were significantly correlated with postural changes,aiming to provide reference for the clini-cal diagnosis,treatment,and research of the disease in the future.

Primary central nervous system vasculitis(PACNS)is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and me-ninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.