Cervical cancer (CC) is the fourth leading cause of cancer-related deaths among women worldwide in 2022, and conventional treatment modalities offer limited efficacy for patients with advanced or recurrent disease. Natural killer (NK) cells are a subset of lymphocytes capable of non-specifically eliminating tumor cells and virus-infected cells without prior sensitization, and have emerged as a research focus in the field of cancer immunotherapy. However, the systematic elucidation and in-depth analysis are required in the dual regulatory mechanisms of NK cells within the cervical cancer microenvironment and the bottlenecks hindering their clinical translation. This article reviews the application of NK cell-based immunotherapy in CC, summarizes the mechanisms of action and therapeutic advances of NK cells in CC, identifies the major obstacles to current clinical translation, and proposes corresponding solutions.

Objective To investigate the effect of pneumoperitoneum pressure during robotic-assisted kidney transplantation (RAKT) on the function of the transplant kidney. Methods The data of 243 kidney transplant recipients were retrospectively analyzed and divided into open kidney transplantation (OKT) group (n=105) and RAKT group (n=138). The RAKT group was further divided into 13 mmHg group (n=67) and 7 mmHg group (n=71) based on pneumoperitoneum pressure. The donor information, recipient's preoperative general data, intraoperative data, and postoperative recovery of the three groups were compared. In the RAKT group, the renal artery, segmental artery, interlobar artery, and venous flow velocity of the transplant kidney were measured using laparoscopic ultrasound. Results There was a statistically significant difference in donor types among the groups (P<0.05), while other donor information and recipient's preoperative general data showed no statistically significant differences (all P>0.05). There were no statistically significant differences in serum creatinine and complications at 30 days and 1 year postoperatively among the groups (all P>0.05). The OKT group and 7 mmHg group had more intraoperative urine output than the 13 mmHg group. Both RAKT groups had less intraoperative blood loss and shorter hospital stays than the OKT group, and longer operation times than the OKT group (all P<0.05). There were no statistically significant differences in operation time, intraoperative blood loss, and hospital stay between the two RAKT groups (all P>0.05). The vascular flow velocity of the transplant kidney decreased at 13 mmHg compared to 7 mmHg pneumoperitoneum pressure, but the differences were not statistically significant (all P>0.05). Conclusions Controllable pneumoperitoneum pressure has a limited impact on the vascular flow velocity of the transplanted kidney. RAKT is a safe and effective surgical method under appropriate pneumoperitoneum pressure, and choosing a lower pneumoperitoneum pressure is more conducive to the early recovery of renal function postoperatively.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To analyze the clinical characteristics of drug-induced liver injury(DILI)caused by different drug categories,and to investigate factors influencing DILI prognosis.Methods Medical records of DILI patients diagnosed in our hospital from January 1,2019 to December 31,2023 were retrospectively collected.Clinical characteristics of DILI induced by different drug categories were analyzed.Multivariate Logistic regression was employed to identify prognostic factors of DILI.Results A total of 347 DILI patients were included.The predominant DILI pattern was hepatocellular injury(67.15％),followed by cholestatic(20.46％)and mixed types(12.39％).The top three causative drug categories were traditional Chinese medicine(25.34％),antineoplastic drugs(24.15％)and anti-infective agents(21.26％).Regarding prognosis outcomes,7 cases(2.02％)achieved complete recovery,269 cases(77.52％)showed improvement,and 71 cases(20.46％)demonstrated no improvement.Significant differences were observed among prognosis groups in age,gender,alanine aminotransferase level,aspartate transaminase level,alkaline phosphatase levels,DILI patterns,number of combined hepatoprotective drugs used,and causative drug categories(P＜0.05).Multivariate analysis revealed that cholestatic type[OR=0.237,95％CI(0.083,0.673),P=0.007]and combination therapy with＞2 hepatoprotective drugs[OR=0.551,95％CI(0.295,0.998),P=0.018]were independent risk factors for prognosis.Conclusion The number of hepatoprotective drugs used in combination and DILI patterns may serve as potential indicators for prognosis evaluation.Particular attention should be paid to the hepatotoxicity of traditional Chinese medicine,antineoplastic agents,and anti-infective drugs.Rational drug selection is essential for improving DILI prevention and treatment.

Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.

Objective To investigate the clinical efficacy and safety of Quhan Tongluo Formula in treating knee osteoarthritis(KOA)of cold-dampness obstruction pattern.Methods A retrospective study was conducted on 231 patients with KOA of cold-dampness obstruction pattern admitted to Dongfang Hospital,Beijing University of Chinese Medicine from December 2022 to December 2023.The patients were divided into an exposed group(105 cases)and a non-exposed group(126 cases)based on whether Quhan Tongluo Formula was applied.The exposed group received Quhan Tongluo Formula combined with celecoxib,while the non-exposed group received only celecoxib.Using propensity score matching based on the baseline data of the medical records,76 pairs(a total of 152 cases)were matched.The changes in Visual Analog Scale(VAS)scores,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)total scores,and traditional Chinese medicine(TCM)syndrome scores before treatment and at 2,4,and 6 weeks after treatment were compared between the two groups,and safety was evaluated.Results Before treatment,there were no significant differences in VAS scores or WOMAC pain scores between the two groups.After treatment,both groups exhibited significant reductions in VAS scores and WOMAC pain scores,with the exposed group demonstrating significantly greater reductions compared to the non-exposed group(P＜0.01).The total clinical effective rate was significantly higher in the exposed group than in the non-exposed group(P＜0.01).Conclusion The clinical application of Quhan Tongluo Formula combined with celecoxib demonstrated superior efficacy over celecoxib monotherapy in treating knee osteoarthritis of cold-dampness obstruction pattern.The combined regimen significantly reduced VAS scores,total WOMAC scores,and TCM syndrome scores,with marked improvements in long-term efficacy.

Objective To analyze the clinical and pathogenic characteristics,as well as influencing factors for the prognosis of patients with Candida bloodstream infection(CBSI).Methods Clinical data of 47 CBSI patients in a hospital from January 2015 to September 2024 were collected.Distribution of departments and infection strains,an-timicrobial resistance,and influencing factors for the poor prognosis of patients were analyzed.Results A total of 51 strains of Candida were detected from 47 CBSI patients,mainly from the intensive care unit(ICU;n=25,53.2％),department of intestinal fistula surgery(n=8,17.0％),and department of respiratory medicine(n=4,8.6％),et al.The main detected pathogens were Candida albicans(n=29,56.9％),Candida tropicalis(n=7,13.7％),Candida glabrata(n=6,11.8％),and Candida parapsilosis(n=6,11.8％).Resistance rate of Candida albi-cans to fluconazole was 11.5％(3/26).According to the prognosis results,patients were divided into a good prog-nosis group(n=26,55.3％)and a poor prognosis group(n=21,44.7％).Univariate analysis showed statistically significant differences between patients in the good prognosis group and the poor prognosis group in terms of abso-lute neutrophil count,ICU admission,mechanical ventilation,tracheal intubation,gastrointestinal hemorrhage/per-foration,and surgical treatment(lesion clearance,drainage or unblocking for obstruction)(all P＜0.05).Prelimi-nary multivariate logistic regression analysis showed that gastrointestinal hemorrhage/perforation was a potential risk factor for the poor prognosis in CBSI patients(OR=11.156,95％CI:1.434-86.809,P=0.021).Conclusion The detected CBSI strains are mainly Candida albicans,and gastrointestinal hemorrhage/perforation may be one of the potential risk factors affecting the prognosis of CBSI patients.These patients are generally in critical condition and should be detected and treated as early as possible to improve their prognosis.Due to the small amount of speci-mens,further research is still needed for confirmation.

Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.