Objective To investigate the association between intraoperative dexamethasone administration and long-term survival outcomes.Methods A total of 1 629 NSCLC patients who underwent lung tumor resection between January 2008 and December 2014 were included in this study.A propensity score-matched cohort was generated at a ratio of 1∶2 to compare patients who received dexamethasone with those who did not.This matching process resulted in a cohort of 532 patients in the non-DEX group and 283 patients in the DEX group.Within this propensity score-matched cohort,disease-free survival(DFS)and overall survival(OS)were compared between the non-DEX and DEX groups using the Kaplan-Meier method.Additionally,Cox proportional hazards regression analysis was used to evaluate the associations between intraoperative administration of dexamethasone and high-risk factors for postoperative nausea and vomiting(PONV),as well as their impact on DFS and OS.Results After propensity score matching,intraoperative dexamethasone was significantly associated with worse OS(P=0.005),while no significant correlation was observed between intraoperative dexamethasone and DFS.Multivariate Cox regression analyses indicated that intraoperative dexamethasone was associated with poorer overall survival(HR=1.233,95%CI:1.002～1.516,P=0.048).In subgroup analyses,intraoperative dexamethasone was significantly associated with shorter OS in the female,video-assisted thoracoscopic surgery(VATS),prolonged anesthetic time,and inhalation anesthesia subgroups.Conclusions There was a significant correlation between intraopera-tive dexamethasone administration and overall survival in NSCLC patients following curative surgery.In high-risk subgroups for PONV,including females,those undergoing VATS,patients with prolonged anesthetic duration,and those under inhalation anesthesia,the administration of intraoperative dexamethasone was associated with a potentially poorer prognosis compared to patients who did not receive intraoperative dexamethasone.

Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts ( n = 101) and those with low sperm motility or concentration ( n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 ( MAP2K2 ), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.
Male ; Humans ; Spermatozoa/metabolism* ; RNA, Transfer/genetics* ; Sperm Motility/genetics* ; Adult ; Semen Analysis ; Sexual Abstinence/physiology* ; Sperm Count ; DNA Fragmentation

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective:To investigate the clinical characteristics, prevalent serum groups, and drug sensitivity test results of epidemic cerebrospinal meningitis in children in Shanghai area.Methods:The study was a retrospective case-control study. The children hospitalized for epidemic cerebrospinal meningitis in Children′s Hospital of Fudan University from January 2003 to December 2023 were enrolled. Clinical data were collected, including demographic characteristics, clinical manifestations, pathogen detection results, strain typing, and drug sensitivity test results.Results:A total of 77 children with confirmed epidemic cerebrospinal meningitis were hospitalized, including 50 males (64.94%) and 27 females (35.06%). The age was 24(8, 60) months, with 16 cases (20.78%) aged 0 to five months, nine cases (11.69%) aged six to 11 months, 21 cases (27.27%) aged 12 to 35 months, 16 cases (20.78%) aged three to five years, 13 cases (16.89%) aged six to 11 years, and two cases (2.60%) aged 12 years. The highest number of cases was in spring, with 36 cases (46.75%), followed by winter with 25 cases (32.47%). Thirty-three cases (42.86%) had vaccinated with meningococcal vaccine. The clinical symptoms included fever in all 77 cases (100.00%), skin petechiae and ecchymosis in 58 cases (75.32%), vomiting in 56 cases (72.73%), respiratory symptoms in 12 cases (15.58%), convulsions in 17 cases (22.08%), conscious disturbance in 24 cases (31.17%), shock in 38 cases (49.35%), circulatory failure in 13 cases (16.88%), and respiratory failure in seven cases (9.09%). Among the 77 children, fifty-seven cases (74.03%) were common type and 20 cases (25.97%) were fulminant type, with seven deaths (9.09%). Neisseria meningitidis (Nm) was detected in 55 cases (71.43%), with the positive rates of skin petechiae smear and cerebrospinal fluid smear of 23.26%(10/43) and 19.44%(14/72), respectively. The positive rates of cerebrospinal fluid culture and blood culture were 36.51%(23/63) and 31.51% (23/73), respectively. The positive rate of polymerase chain reaction detection was 79.17%(38/48). The serogroups were determined in the 38 Nm strains, including 18 cases (47.37%) of group B, 14 cases (36.84%) of group C, five cases (13.16%) of group A, and one case (2.63%) of group Y. Among the 29 Nm strains tested for antimicrobial susceptibility, one strain (3.45%) was resistant to penicillin, two strains (6.90%) were resistant to cefotaxime, 21 strains (72.41%) were resistant to ciprofloxacin, and 25 strains (86.21%) were resistant to sulfamethoxazole/trimethoprim. All strains were sensitive to ceftriaxone, azithromycin, meropenem, rifampicin, chloramphenicol, and minocycline. Conclusions:Epidemic cerebrospinal meningitis presents a low prevalence trend in children in Shanghai area. Infants and toddlers remain the major susceptible individuals. Nm has reduced sensitivity to penicillin, but remains sensitive to ceftriaxone. Ceftriaxone is recommended as the first-line choice for antibiotic therapy. The prevalent serogroups are Group B, Group C, Group A and Group Y in sequence. Immunization plan adjustment should be suggested. Vaccination covering the current epidemic serum population as early as possible should be recommended.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective To investigate the association between intraoperative dexamethasone administration and long-term survival outcomes.Methods A total of 1 629 NSCLC patients who underwent lung tumor resection between January 2008 and December 2014 were included in this study.A propensity score-matched cohort was generated at a ratio of 1∶2 to compare patients who received dexamethasone with those who did not.This matching process resulted in a cohort of 532 patients in the non-DEX group and 283 patients in the DEX group.Within this propensity score-matched cohort,disease-free survival(DFS)and overall survival(OS)were compared between the non-DEX and DEX groups using the Kaplan-Meier method.Additionally,Cox proportional hazards regression analysis was used to evaluate the associations between intraoperative administration of dexamethasone and high-risk factors for postoperative nausea and vomiting(PONV),as well as their impact on DFS and OS.Results After propensity score matching,intraoperative dexamethasone was significantly associated with worse OS(P=0.005),while no significant correlation was observed between intraoperative dexamethasone and DFS.Multivariate Cox regression analyses indicated that intraoperative dexamethasone was associated with poorer overall survival(HR=1.233,95%CI:1.002～1.516,P=0.048).In subgroup analyses,intraoperative dexamethasone was significantly associated with shorter OS in the female,video-assisted thoracoscopic surgery(VATS),prolonged anesthetic time,and inhalation anesthesia subgroups.Conclusions There was a significant correlation between intraopera-tive dexamethasone administration and overall survival in NSCLC patients following curative surgery.In high-risk subgroups for PONV,including females,those undergoing VATS,patients with prolonged anesthetic duration,and those under inhalation anesthesia,the administration of intraoperative dexamethasone was associated with a potentially poorer prognosis compared to patients who did not receive intraoperative dexamethasone.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective:To investigate the clinical characteristics, prevalent serum groups, and drug sensitivity test results of epidemic cerebrospinal meningitis in children in Shanghai area.Methods:The study was a retrospective case-control study. The children hospitalized for epidemic cerebrospinal meningitis in Children′s Hospital of Fudan University from January 2003 to December 2023 were enrolled. Clinical data were collected, including demographic characteristics, clinical manifestations, pathogen detection results, strain typing, and drug sensitivity test results.Results:A total of 77 children with confirmed epidemic cerebrospinal meningitis were hospitalized, including 50 males (64.94%) and 27 females (35.06%). The age was 24(8, 60) months, with 16 cases (20.78%) aged 0 to five months, nine cases (11.69%) aged six to 11 months, 21 cases (27.27%) aged 12 to 35 months, 16 cases (20.78%) aged three to five years, 13 cases (16.89%) aged six to 11 years, and two cases (2.60%) aged 12 years. The highest number of cases was in spring, with 36 cases (46.75%), followed by winter with 25 cases (32.47%). Thirty-three cases (42.86%) had vaccinated with meningococcal vaccine. The clinical symptoms included fever in all 77 cases (100.00%), skin petechiae and ecchymosis in 58 cases (75.32%), vomiting in 56 cases (72.73%), respiratory symptoms in 12 cases (15.58%), convulsions in 17 cases (22.08%), conscious disturbance in 24 cases (31.17%), shock in 38 cases (49.35%), circulatory failure in 13 cases (16.88%), and respiratory failure in seven cases (9.09%). Among the 77 children, fifty-seven cases (74.03%) were common type and 20 cases (25.97%) were fulminant type, with seven deaths (9.09%). Neisseria meningitidis (Nm) was detected in 55 cases (71.43%), with the positive rates of skin petechiae smear and cerebrospinal fluid smear of 23.26%(10/43) and 19.44%(14/72), respectively. The positive rates of cerebrospinal fluid culture and blood culture were 36.51%(23/63) and 31.51% (23/73), respectively. The positive rate of polymerase chain reaction detection was 79.17%(38/48). The serogroups were determined in the 38 Nm strains, including 18 cases (47.37%) of group B, 14 cases (36.84%) of group C, five cases (13.16%) of group A, and one case (2.63%) of group Y. Among the 29 Nm strains tested for antimicrobial susceptibility, one strain (3.45%) was resistant to penicillin, two strains (6.90%) were resistant to cefotaxime, 21 strains (72.41%) were resistant to ciprofloxacin, and 25 strains (86.21%) were resistant to sulfamethoxazole/trimethoprim. All strains were sensitive to ceftriaxone, azithromycin, meropenem, rifampicin, chloramphenicol, and minocycline. Conclusions:Epidemic cerebrospinal meningitis presents a low prevalence trend in children in Shanghai area. Infants and toddlers remain the major susceptible individuals. Nm has reduced sensitivity to penicillin, but remains sensitive to ceftriaxone. Ceftriaxone is recommended as the first-line choice for antibiotic therapy. The prevalent serogroups are Group B, Group C, Group A and Group Y in sequence. Immunization plan adjustment should be suggested. Vaccination covering the current epidemic serum population as early as possible should be recommended.

Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.