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]

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ²=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ²=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ²=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ²=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ²=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.
Humans ; Pelvic Exenteration/methods* ; Retrospective Studies ; Treatment Outcome ; Blood Loss, Surgical ; Laparoscopy/methods* ; Rectal Neoplasms/surgery*

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction. Sperm protein antigen 17 (SPA17) can also bind to AKAP. This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI (H-DFI) patients during IVF-ET. In addition, the study investigates the expression of AKAP, protein kinase A regulatory subunit (PKARII), and SPA17 between H-DFI and low sperm DFI (L-DFI) patients. SPA17 at the transcriptional level is abnormal, the translational level increases in H-DFI patients, and the expression of AKAP4/PKARII protein decreases. H2O2 has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI. It indicates that H2O2 increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARII protein expression. These processes inhibit sperm capacitation and reduce acrosomal reactions. Embryo culture data and IVF outcomes have been documented. The H-DFI group has a lower fertilization rate. Therefore, the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARII proteins, blocked sperm capacitation, and reduced occurrence of acrosome reaction.

OBJECTIVE: To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay. RESULTS: Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells. CONCLUSION Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.
Humans ; Cyclin B1/pharmacology* ; Cell Proliferation ; Methionine/pharmacology* ; Cell Cycle ; Apoptosis ; Leukemia, Myeloid, Acute ; Cell Division ; Cell Cycle Proteins ; Jurkat Cells ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; HL-60 Cells

Objective To compare the pharmaceutics and drug interactions of noiiglutide injection,INS068 injection,HR17031 Injection,and noiiglutide+INS068 injection in healthy subjects Methods This was a single center,randomized,open-label,4-cycle,4-cohort trial.Healthy subjects were allocated to 4 groups randomly.HR17031(17 U/0.04 mg),INS068(17 U),noliglycopeptide(0.04 mg),and INS068(17 U)combined with noiiglutide(0.04 mg)were injected subcutaneously into the abdomenon on day 1,8,15 and 22 respectively.Venous blood was collected at different timing before and after administration,and the concentrations of noiiglutide in plasma and INS068 in serum were measured by HPLC-MS/MS method.Relevant pharmacokinetic parameters were calculated using the WinNonlin non compartment model.Results In HR17031,INS068,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of INS068 in serum were calculated and listed as follows:Cmax were(19.50±4.06),(18.10±4.56)and(18.40±5.81)ng·mL-1,tmax was 12,10 and 8 h,t1/2 was(9.27±1.70),(11.00±2.81)and(11.0±3.18)h,AUC0-twere(505.00±62.20),(498.00±70.50)and(491.00±74.20)ng·mL-1·h.In HR17031,noiiglutide,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of noiiglutide in plasma were calculated and listed as follows:Cmax were(3.61±0.82),(4.63±0.87)and(4.54±0.86)ng·mL-1,tmax was all 8.00 h,t1/2 was(10.50±1.61),(9.49±1.40)and(9.55±1.61)h,AUC0-twere(94.30±20.10),(106.00±20.20)and(105.00±19.00)ng·mL-1·h.Conclusion There was no significant difference in bioavailability of INS068 and noiiglutide in HR17031 compared with INS068 and noiiglutide whether combined or used alone.