OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

Objective To understand the current situation of protective mask wearing behavior of health care workers(HCWs),analyze the influencing factors for the failure to wear medical protective masks in a standard manner,and provide basis for the improvement of mask-wearing related training.Methods From June 2022 to March 2023,staff in a tertiary first-class hospital were selected as the research object.Real-time quantitative fitness testing using aerosol condensation particle counting method was applied to test 5 commonly used medical protective masks available in the market.Fitness factor changes of the testing instrument and assistance from professional per-sonnel were needed to comprehensively estimate the wearing condition of medical protective masks.Participants were surveyed through a self-made general information questionnaire.Heads and faces of participants were scanned by three-dimensional(3D)laser scanning technology,and scanned images were imported into Geomagic Studio 2013 software to measure head and face dimensions.Results A total of 222 HCWs were investigated,991 real-time tests and 208 times of 3D scanning were conducted.221(22.30％)tests showed failure of participants in wearing masks in a standard manner.The non-standard wearing rates of 5 types of medical protective masks were 30.56％,25.62％,25.87％,23.15％,and 7.35％,respectively.The non-standard mask-wearing rates showed statistically significant difference between groups categorized in terms of medical protective masks with different shapes,partici-pants'occupation,time of last training for wearing medical protective masks,and participants'experience in pre-vention and control of respiratory infectious disease(all P＜0.05).There were no statistically significant differences in non-standard mask-wearing rate between groups with different brands and sizes of medical protective masks,as well as gender and department of participants,etc.(all P＞0.05).The body mass index(BMI)was significantly different among participants who wear foldable medical protective masks in the standard and non-standard manner(both P＜0.05).Conclusion Wearing medical protective masks by HCWs in a non-standard manner is influenced by multiple factors.It is recommended to conduct real-time testing before formal quantitative fitness testing,so as to save time and improve testing efficiency.When conducting training on wearing medical protective masks in the fu-ture,targeted training should be provided based on mask shape and focus on logistics personnel,interns,individuals with high BMI,those who have never received training on wearing medical protective masks,and those who have never participated in the prevention and treatment of respiratory infectious diseases.

Aim To construct CX3CR1GFP transgenic mice based on the Cre/Loxp system,and to analyze the expression efficiency of CX3CR1GFP.Methods Targeted vectors were designed using restriction enzyme-based cloning technology to create a linearized targeted vector for transfecting embryonic stem cells(ES).The ES cells with a deletion of the neomycin resistance gene(neo)were then cloned into blastocysts to generate chimeric CX3CR1+/GFPmice.These mice were subsequently bred with wild-type mice(WT),and repeated backcrossing was performed to obtain CX3CR1GFP/GFP mice.DNA and mRNA from WT and CX3CR1GFP mice were extracted and genotyped using agarose gel electrophoresis.The expression level of CX3CR1 in various tis-sues of the mice was detected by RT-qPCR.Western blot analy-sis was used to analyze the expression of GFP protein in periph-eral blood mononuclear cells(PBMC)and various tissues.The labeling efficiency of immune cells in bone marrow was detected by flow cytometry.The expression of GFP in different mouse tis-sues was observed by immunofluorescence.Results The results of agarose gel electrophoresis showed that the transgenic mouse genotype was CX3CR1GFP/GFP homozygote.RT-qPCR and West-ern blot showed that EGFP were targeted to replace CX3CR1 gene,so CX3CR1 expression was very low in CX3CR1GFP mice,while GFP expression was significantly upregulated.Flow cytom-etry and immunofluorescence showed that GFP effectively marked CX3CR1GFP mice,expressed in various tissues and cells with different expression levels.Conclusion This study con-structs and identifies the CX3CR1GFP genetic reporter mice,and GFP is stably expressed in mice,which provides a foundation for further research into the potential mechanisms of CX3CR1 in im-mune regulation.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Aim To investigate the eorrelation between angiotensin II (Ang II ) level and clinical indicators in patients with rheumatoid arthritis ( HA) , and to determine the therapeutic effect of angiotensin receptor blockers ( ARBs).Methods Plasma samples and personal information were collected from HA patients admitted to our hospital from 2019 to 2021.The level of Ang II in plasma was determined by ELISA to elucidate the correlation between plasma Ang II level and the severity of HA.The pathological changes of synovi-al tissues and T eells subtype in different groups of HA patients were determined by pathological examination and flow cytometry.A rat model of collagen-induced arthritis (CIA) was established and the pathological examination was used to confirm that valsartan could alleviate the disease course in the CIA animal model.Results Compared with control group, the plasma level of Ang II in HA patients significantly increased.After therapy with oral ARBs plasma Ang H levels and anti - cyclic citrullinated peptide antibody ( CCP) titre were significantly lower than those untreated HA patients.The level of Ang II in plasma was positively correlated with CCP and the number of monocytes, but negatively with number of RBC and hemoglobin content.Staining of synovial tissue with HE and Masson found that patients with HA had significant synovial proliferation, pannus formation , and numerous inflammatory cell infiltrates compared with control patients.Immunohistochemical results showed significant infiltration of CD4 4 T cells in synovial tissues of HA patients.Western blot and immunofluorescence analysis showed that the expression of angiotensin type 1 receptor ( ATI R ) was significantly up-regulated in CD4 + T cells and synovial tissues of HA patients.The results of animal experiments showed that valsartan harl therapeutic effect on CIA rats and could delay the disease process of CIA.Conclusions Plasma Ang II level is positively correlated with CCP level and HA severity.ARBs can down-regualte CCP level and delay disease progression in HA patients.Animal experiments showed that valsartan blocks the combination of Ang H and ATI R and has therapeutic effect on a CIA rat model.This study provides the theoretical and experimental basis for ARBs to become the preferred antihypertensive drugs for HA patients with hypertension.

To explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a classical prescription, in improving testicular aging(TA) in vivo, the authors randomly divided 24 male rats into four groups: the normal, model, DHZCP and vitamin E(VE) groups. The TA rat model was established by continuous gavage of D-galactose(D-gal). During the experiment, the rats in the DHZCP and VE groups were given DHZCP suspension and VE suspension, respectively by gavage, while those in the normal and model groups were gavaged saline separately every day. After the co-administration of D-gal and various drugs for 60 days, all rats were sacrificed, and their blood and testis were collected. Further, various indexes related to TA and necroptosis of testicular cells in the model rats were examined and investigated, which included the aging phenotype, total testicular weight, testicular index, histopathological features of testis, number of spermatogenic cells, sex hormone level, expression characteristics of reactive oxygen species(ROS) in testis, expression levels and characteristics of cyclins in testis, and protein expression levels of the key molecules in receptor-interacting serine/threonine-protein kinase 1(RIPK1)/receptor-interacting serine/threonine-protein kinase 3(RIPK3)/mixed lineage kinase domain like pseudokinase(MLKL) signaling pathway in each group. The results showed that, for the TA model rats, both DHZCP and VE improved their aging phenotype, total testicular weight, testicular index, pathological features of testis, number of spermatogenic cells, serum testosterone and follicle stimulating hormone levels, expression characteristics of ROS and protein expression levels and characteristics of P21 and P53 in testis. In addition, DHZCP and VE improved the protein expression levels of the key molecules in RIPK1/RIPK3/MLKL signaling pathway in testis of the model rats. Specifically, DHZCP was better than VE in the improvement of RIPK3. In conclusion, in this study, the authors found that DHZCP, similar to VE, ameliorated D-gal-induced TA in model rats in vivo, and its mechanism was related to reducing necroptosis of testicular cells by inhibiting the activation of RIPK1/RIPK3/MLKL signaling pathway. This study provided preliminary pharmacological evidence for the development and application of classical prescriptions in the field of men's health.
Aging ; Animals ; Drugs, Chinese Herbal ; Male ; Necroptosis ; Protein Kinases/genetics* ; Rats ; Reactive Oxygen Species/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/pharmacology* ; Serine/pharmacology* ; Signal Transduction ; Testis ; Threonine/pharmacology*

OBJECTIVE: To investigate the gene-carrying rate and genetic types of thalassemia among the couples of child-bearing age in Ding'an, Hainan province. METHODS: A total of 1742 couples at child bearing age in the region were screened for thalassemia by detecting the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). If the sample data of either spouse of couples was tested as MCV＜82 fl and /or MCH＜27 pg, both samples of the couple would be further assayed by hemoglobin electrophoresis. Those samples of HbA2 2.5 % or HbA2＞3.5 % were judged as positive in the preliminary screening, then subjected to genetic diagnosis of thalassemia. RESULTS: 478 cases out of 1 742 couples of child bearing age were diagnosed as thalassemia gene mutation, and the gene-carrying rate was 13.72 %. In those carriers, 42 couples were diagnosed with the same type of thalassemia, accounting for 3.67 %. The gene-carrying rate of α-thalassemia, β-thalassemia and αβ-thalassemia was 9.56%, 3.10% and 1.06 % respectively. CONCLUSION The Ding'an area in Hainan Province is an area with high incidence of thalassemia, and the main genotype is α-thalassemia, showing a distribution of local characteristics. The government should make efferts to popularise the screening for thalassemia, so as to effectively prevent the birth of children with thalassemia major.
Erythrocyte Indices ; Genetic Testing ; Heterozygote ; Humans ; alpha-Thalassemia ; beta-Thalassemia

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

OBJECTIVE: To determine the incidence of surgical site infection (SSI) after abdominal surgery and to further evaluate the related risk factors of SSI in China. METHODS: The multicenter cross-sectional study collected clinical data of all adult patients who underwent abdominal surgery from May 1, 2018 to May 31, 2018 in 30 domestic hospitals, including basic information, perioperative parameters, and incisional microbial culture results. The primary outcome was the incidence of SSI within postoperative 30 days. SSI was classified into superficial incision infection, deep incision infection, and organ/gap infection according to the US Centers for Disease Control and Prevention (CDC) criteria. The secondary outcome variables were ICU stay, postoperative hospital stay, total hospital stay, 30-day mortality and treatment costs. Multivariate logistic regression was used to analyze the risk factors of SSI. RESULTS: A total of 1666 patients were enrolled in the study, including 263 cases of East War Zone Hospital of PLA, 140 cases of Affiliated Hospital of Qingdao University, 108 cases of The First Affiliated Hospital of Nanchang University, 87 cases of Central War Zone Hospital of PLA, 77 cases of West China Hospital, 74 cases of Guangdong General Hospital, 71 cases of Chenzhou First People's Hospital, 71 cases of Zigong First People's Hospital, 64 cases of Zhangjiagang First People's Hospital, 56 cases of Nanyang City Central Hospital, 56 cases of Lanzhou General Hospital of Lanzhou Military Command, 56 cases of Shandong Provincial Hospital, 52 cases of Shangqiu First People's Hospital, 52 cases of People's Hospital of Xinjiang Uygur Autonomous Region, 48 cases of The Second Xiangya Hospital of Central South University, 48 cases of Chinese PLA General Hospital, 44 cases of Affiliated Hospital of Xuzhou Medical University, 38 cases of Hunan Province People's Hospital, 36 cases of Dongguan Kanghua Hospital, 30 cases of Shaoxing Central Hospital, 30 cases of Northern Jiangsu People's Hospital, 29 vases of The First Affiliated Hospital of Zhengzhou University, 27 cases of General Hospital of Tianjin Medical University, 22 cases of Zigong Fourth People's Hospital, 21 cases of The Second Hospital of University of South China, 18 cases of Tongji Hospital, 15 cases of Nanchong Central Hospital, 12 cases of The 901th Hospital of PLA, 11 cases of Hunan Cancer Hospital, 10 cases of Lanzhou University Second Hospital. There were 1019 males and 647 females with mean age of (56.5±15.3) years old. SSI occurred in 80 patients (4.8%) after operation, including 39 cases of superficial incision infection, 16 cases of deep incision infection, and 25 cases of organ/interstitial infection. Escherichia coli was the main pathogen of SSI, and the positive rate was 32.5% (26/80). Compared with patients without SSI, those with SSI had significantly higher ICU occupancy rate [38.8%(31/80) vs. 13.9%(220/1586), P<0.001], postoperative hospital stay (median 17 days vs. 7 days, P<0.001) and total hospital stay (median 22 days vs. 13 days, P<0.001), and significantly higher cost of treatment (median 75 000 yuan vs. 44 000 yuan, P<0.001). Multivariate analysis showed that male rise(OR=2.110, 95%CI:1.175-3.791, P=0.012), preoperative blood glucose level rise(OR=1.100, 95%CI: 1.012-1.197, P=0.026), operative time (OR=1.006, 95%CI:1.003-1.009, P<0.001) and surgical incision grade (clean-contaminated incision:OR=10.207, 95%CI:1.369-76.120, P=0.023; contaminated incision: OR=10.617, 95%CI:1.298-86.865, P=0.028; infection incision: OR=20.173, 95%CI:1.768-230.121, P=0.016) were risk factors for SSI; and laparoscopic surgery (OR=0.348, 95%CI:0.192-0.631, P=0.001) and mechanical bowel preparation(OR=0.441,95%CI:0.221-0.879, P=0.020) were protective factors for SSI. CONCLUSIONS The incidence of postoperative SSI in patients with abdominal surgery in China is 4.8%. SSI can significantly increase the medical burden of patients. Preoperative control of blood glucose and mechanical bowel preparation are important measures to prevent SSI.
Abdomen ; surgery ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; General Surgery ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Operative Time ; Postoperative Complications ; prevention & control ; Preoperative Period ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection ; prevention & control