Objective To investigate the impact of anesthesia and surgery on hippocampal expression of Alzheimer’s disease (AD)-associated proteins in 5×FAD transgenic mice and explore potential sex differences. Methods 5×FAD mice were crossbred with C57BL/6J wild-type (WT) mice to generate offspring for genotypic confirmation. Four-month-old 5×FAD mice and littermate (LM) WT controls were allocated into 8 experimental groups (n＝8/group): female/male 5×FAD control group, female/male 5×FAD anesthesia/surgery group, female/male LM control group, and female/male LM anesthesia/surgery group. Anesthesia/surgery groups underwent laparotomy under 1.4% isoflurane anesthesia, while control groups received no intervention. Hippocampal tissues were collected 24 hours post-procedure for Western blotting analysis of β-catenin, glycogen synthase kinase 3 beta (GSK3β), and phosphorylated GSK3β (p-GSK3β) levels. Results Female 5×FAD mice demonstrated significant reductions in β-catenin levels and p-GSK3β expression compared to both sex-matched LM controls and male 5×FAD counterparts (P＜0.05). No significant differences in these proteins were observed in male 5×FAD mice following anesthesia/surgery. Conclusions These findings reveal sex-specific responses to perioperative stress in AD, suggesting that anesthesia and surgery may affect female AD patients through hippocampal β-catenin/GSK3β pathway modulation.

OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

Objective:To investigate the effectiveness and safety of the coaxial needle technique in percutaneous liver biopsy for patients with coagulation function abnormalities.Methods:Clinical data of 210 patients who underwent percutaneous liver biopsy using the coaxial needle technique under ultrasound guidance from December 2018 to May 2021 in 3 centers were collected. A retrospective analysis was conducted to compare the puncture success rate, number of samples obtained, pathology qualification rate, intraoperative and postoperative bleeding rates between the group with coagulation function abnormalities and the group with normal coagulation function.Results:After propensity score matching, there were 105 patients in each group, with a puncture success rate of 100% in both groups. The pathology qualification rate was 100% for all samples.Intraoperative bleeding occurred in 78 cases (74.3%, 78/105) in the coagulation function abnormalities group and in 64 cases (61.0%, 64/105) in the normal coagulation function group, with a statistically significant difference between the two groups ( P=0.006). Postoperative bleeding occurred in 3 cases (2.9%, 3/105) in the coagulation function abnormalities group and in 0 case in the normal coagulation function group, with no statistically significant difference between the two groups ( P=0.081). Conclusions:The use of the coaxial needle technique for percutaneous liver biopsy in patients with coagulation function abnormalities not only allows for obtaining an adequate tissue sample but also demonstrates good safety.

Oncocytoma is a benign tumor of the salivary gland.Its incidence is very low and very seldom documen-ted in literature.Clear-cell dominant oncocytoma is even less common.The tumor's clinical symptoms and imaging re-sults are nonspecific,so distinguishing other salivary gland tumors(such as oncocytic carcinoma)from clear-cell renal carcinoma is difficult,possibly leading to misdiagnosis and maltreatment.Here,a case of clear-cell dominant oncocyto-ma was presented,and the relevant literature was evaluated to investigate the diagnosis and management of clear-cell dominant oncocytoma.

Background and objective Tumor microenvironment(TME)is one of the important factors in tu-morigenesis and progression,in which tumor-associated macrophages(TAMs)play an important role in non-small cell lung cancer(NSCLC)progression.However,the mechanism of TAMs in NSCLC progression remains unclear,so this study aimed to investigate the role of TAMs in NSCLC progression and to find potential therapeutic targets.Methods Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the expression of prostaglandin E2 receptor 4(EP4)mRNA in NSCLC and normal lung tissues;the protein expression levels of cyclooxygenase-2(COX-2),EP4,cluster of differentiation 86(CD86),CD163 and CD31 were detected by immunohistochemistry(IHC)in 120 NSCLC tissues and 24 paracancerous tissues specimens.The nude mouse lung adenocarcinoma cell A549 and macrophage RAW264.7 co-transplanted tumor model was established.And the samples were collected by gavage with EP4 inhibitor E7046,and then stained with hematoxylin-eosin(HE),IHC,and immunofluorescence(IF),and then detected by Western blot for the epithelial mesenchymal transformation(EMT)of the tumor tissues of the nude mice in each group.Western blot was used to detect the expressions of EMT related protiens in each group of nude mice;full-length transcriptome sequencing was used to screen the key genes causing liver me-tastasis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results EP4 mRNA expression level in NSCLC tissues was generally lower than that in normal lung tissues(P<0.05);COX-2,EP4,CD163,CD31 proteins were differentially expressed in NSCLC tissues and adjacent tissues,and differences were observed in many clinico-pathological parameters of NSCLC patients;RAW264.7 shortened the latency period of tumorigenesis of A549 and promoted the proliferation of tumors and liver metastasis of tumors,and E7046 could reduce tumor cell proliferation activity,tumor tissue vascular density and M2-type macrophage infiltration in nude mice;IF staining showed that macrophages were mainly distributed around the metastatic foci of tumors;Western blot results showed that compared with A549 alone transplantation group,the relative expression of E-cadherin protein in tumor tissues of mice in A549 and RAW264.7 co-transplantation group was significantly decreased,and the difference was statistically significant(P<0.05),while the relative expression of N-cadherin protein was up-regulated,but the difference was not statistically significant(P>0.05);the main pathways enriched in the differ-ential genes of the full-length transcriptome were the PI3K-AKT and MAPK signaling pathways.Conclusion During NSCLC development,the COX-2/PGE2/EP4 axis may promote tumor progression by inducing macrophage functional activation,and EP4 may be a potential new target for tumor immunotherapy.This study provides new perspectives and ideas for in-depth exploration of the mechanisms of NSCLC development,as well as a theoretical basis for the development of new therapeutic strategies for NSCLC.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Objective To explore the effects and influencing factors of traditional occupational health training on occupational health literacy (OHL) of employees in micro-, small- and medium-sized enterprises. Methods A total of 540 employees from 154 micro-, small- and medium-sized enterprises, who participated (347 employees) and not-participated (193 employees) in traditional occupational health training, and 171 community residents/students (not-participated in occupational health training) were selected as the research subjects using the convenient sampling method. The OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations. Results The overall OHL level of employees was 43.3% (234/540). Among them, the overall OHL level of untrained and trained employees was 38.9% and 45.8%, respectively, and the overall OHL level of community residents/students was 43.3%. The results of multivariate logistic regression analysis showed that the higher the educational level, the higher the OHL level (all P<0.01). The OHL level of untrained and trained employees was higher than that of untrained community residents/students (all P<0.05). The interaction of education level and training status had no statistical difference on the OHL level of the research subjects (P>0.05). The results of factorial design analysis of variance showed that the overall OHL score rate of untrained employees and trained employees was higher than that of untrained community residents/students (all P<0.05). However, there was no significant difference in overall OHL score rate between untrained and trained employees (P>0.05). Conclusion The role of traditional occupational health training in improving the OHL level of employees in micro-, small- and medium-sized enterprises needs to be improved. The responsibility of enterprise occupational health training should be implemented, and multiple measures should be taken to enrich the ways and approaches of occupational health education for enterprise employees, to effectively improve the OHL of workers.

Objective:To analyze the biological characteristics, phylogenic features and clinical significance of SQ219 and SQ220 isolated from clinical sputum and midstream urine specimens.Methods:The culture and biochemical characteristics of the two strains were observed. VITEK2 System, drug sensitivity testing and MALDI-TOF mass spectrometry were used for bacterial identification. Phylogenetic analysis based on 16S rRNA and core genome was performed. The average nucleotide identity (ANI) based on whole genome sequences was calculated.Results:SQ219 and SQ220 were Gram-stain-negative, aerobic, catalase- and oxidase-positive, and non-motile bacteria. Their optimum growth was observed in NaCl-free medium at 30℃ and pH7. Flexirubin-type pigments were produced by SQ220 on Colombia blood agar, but not by SQ219. Both SQ219 and SQ220 were resistant to aztreonam, amikacin, tobramycin and colistin, which was consistent with the drug resistance phenotype of genus Chryseobacterium. The genome sequences of SQ219 and SQ220 were 5.08 Mb and 4.80 Mb in length, and the G+ C contents were 36.72% and 36.36%, respectively. Both strains carried β-lactam resistance gene ( blaCGA). 16S rRNA phylogenetic analysis showed that SQ219 and SQ220 were closely related to Chryseobacterium gambrini DSM18014 T with the similarities of 98.93% and 98.36%, respectively. Core genome phylogenetic analysis revealed that SQ219 and SQ220 were highly homologous to Chryseobacterium gambrini DSM18014 T. However, the ANI values between the two strains and Chryseobacterium gambrini DSM18014 T were 92.49% and 93.27%, respectively, below the threshold for prokaryotic species identification. Conclusions:Based on the phenotypic and phylogenetic data, SQ219 and SQ220 represent a novel species of the genus Chryseobacterium. This study would help promote the understanding of the evolution of Chrysobacterium and provide reference for the identification of new species of Chrysobacterium.

Objective:To explore the effect of high intensity interval training (HIIT) on cardiac rehabilitation in patients after heart transplantation.Methods:According to the search terms, the search was conducted on China National Knowledge Infrastructure, VIP, WanFang Data, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Embase, and EBSCO. The search time limit was from the establishment of the database to January 31, 2022. After 2 researchers screened the article, extracted information, and evaluated the quality, a Meta-analysis was conducted using RevMan 5.4 software.Results:According to the inclusion and exclusion criteria, 10 English articles were selected, including 191 patients in the intervention group and 212 patients in the control group, with a total of 403 patients. Meta-analysis showed that during cardiac rehabilitation exercise in patients after heart transplantation, HIIT could improve peak oxygen uptake in cardiopulmonary function exercise testing [ MD=1.98, 95% confidence interval ( CI) (0.55, 3.41), P=0.007], peak heart rate in chronotropic responses [ MD=6.93, 95% CI (2.62, 11.24), P=0.002], and muscle exercise ability [ MD=337.18, 95% CI (12.02, 62.35), P=0.04]. There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, peak systolic blood pressure, peak diastolic blood pressure, resting heart rate and respiratory exchange rate between the two groups ( P>0.05). A subgroup analysis of peak oxygen uptake was conducted based on the intervention period and the start time of rehabilitation exercise after heart transplantation. The results showed that there were statistically significant differences in peak oxygen uptake between the intervention group and the control group when the intervention period was ≤ 12 weeks or the start time was > 6 weeks ( P<0.01) . Conclusions:HIIT effectively improves the peak oxygen uptake, peak heart rate, and muscle exercise activity of patients after heart transplantation. HIIT has a significant impact on peak oxygen uptake when the rehabilitation exercise start time after heart transplantation is > 6 weeks or the intervention period is ≤ 12 weeks.