AIM:This study aims to investigate the effects of aerobic exercise on hypothalamic autophagy and central leptin resistance in obese mice,and to explore the potential mechanisms.METHODS:Forty male C57BL/6J mice,aged 7 to 8 weeks,were randomly assigned to 5 groups:normal control(CON)group,high-fat diet(HFD)group,HFD+exercise(HFD+Exe)group,HFD+phosphate-buffered saline(PBS)group,and HFD+rilmenidine(autophagy ago-nist)group,with 8 mice in each group.Additionally,twelve fibronectin type Ⅲ domain-containing protein 5(Fndc5)gene(encoding irisin precursor protein)knockout(Fndc5 KO)mice were randomly allocated to Fndc5 KO+HFD group and Fndc5 KO+HFD+Exe group,with 6 mice in each group.All mice were fed for 28 weeks.The mice in CON group re-ceived a normal diet,while those in the remaining groups were provided with an HFD.The mice in HFD+Exe and Fndc5 KO+HFD+Exe groups engaged in aerobic treadmill exercise while continuing an HFD from weeks 17 to 28.The mice in HFD+PBS group received intraperitoneal injections of PBS as a control,while those in HFD+rilmenidine group received in-traperitoneal injections of rilmenidine(10 mg?kg-1?d-1),4 times a week over a total duration of 12 weeks(weeks 17 to 28).Following the intervention,serum metabolite levels,as well as concentrations of leptin and irisin,were quantified by ELISA.Morphological alterations in the liver and white adipose tissues were evaluated through oil red O staining and he-matoxylin-eosin(HE)staining.Western blot was utilized to assess the hypothalamic protein levels of autophagy markers,autophagy-related protein 7(ATG7),beclin-1,microtubule-associated protein 1 light chain 3(LC3)and p62,and leptin resistance markers,suppressor of cytokine signaling 3(SOCS3)and protein tyrosine phosphatase 1B(PTP1B).RE-SULTS:Observations of mouse phenotypes indicated that HFD feeding significantly increased body weight,blood lipid content and serum leptin level(P<0.05).The results of HE and oil red O staining demonstrated that HFD feeding marked-ly promoted lipid accumulation in the liver and caused ballooning of white adipocytes.Western blot analyses revealed that HFD feeding significantly down-regulated the protein levels of ATG7,beclin-1 and LC3-Ⅱ/LC3-I,but up-regulated the pro-tein level of p62(P<0.05),thus reducing cellular autophagy capacity.Furthermore,HFD feeding elevated the protein levels of leptin resistance markers SOCS3 and PTP1B(P<0.05).Aerobic exercise and autophagy agonist were found to partially reverse these changes,enhancing cellular autophagy capacity and alleviating leptin resistance.However,these effects were diminished after knockout of Fndc5 gene,further substantiating the role of irisin in exercise-mediated en-hancement of cellular autophagy and attenuation of leptin resistance.CONCLUSION:Aerobic exercise alleviates hypo-thalamic autophagy defect and central leptin resistance in obese mice,which may be associated with exercise-induced irisin.

Objective: To understand the epidemiological and etiological characteristics of food poisoning event occurred in a school in Hangzhou, Zhejiang, so as to provide reference for the scientific management of related emergencies. Methods: By determining the nature of the event through epidemiological investigation, a case control study was carried out to spot suspicious food in May 2024. The hygienic investigation was conducted to find out possible pollution links and factors, patients and canteen practitioners anal swab, canteen retention samples, catering link daub and other specimens were collected ,for rapid pathogen screening. And the suspected pathogen Clostridium perfringens (CP) were isolated and identified according to the screening results, and toxin gene detection and whole genome sequencing and cluster analysis of CP isolated strains were carried out. Results: The incident resulted in 45 people experiencing gastrointestinal symptoms, such as diarrhea and abdominal pain. The suspicious food was tomato scrambled eggs and corn ribs provided by the student canteen for lunch on May 29. A hygiene investigation found that there was a risk of contamination in the food processing, preparation and storage. A total of 46 anal swabs and 10 canteen retention samples were positive for CP 16 S, 59 strains of CP were isolated from 27 samples, 10 cases and 1 practitioner isolate were positive for CPE ( cpe ) (F mode), and their whole genome evolution analysis was conducted based on the same source. Conclusions The food poisoning event is caused by CP infection carrying CPE ( cpe ) (F mode), and the possible sources of outbreak are the carriers of the CP by employees. It is recommended that cafeteria staff strengthen training on common foodborne diseases and conduct regular monitoring of pathogens.

Fractures requiring surgical intervention during pregnancy is rarely seen in clinic,and these patients need special treatment and nursing,necessitating the consideration of both maternal fracture repair and fetal safety.For patients in late pregnancy,they have higher risk of complications,such as premature birth,placental abruption,venous thromboembolism(VTE),and anesthesia-relat-ed manifestations during the perioperative period.This article reported a case of a patient at 28 weeks of gestation with medial and lateral malleolar fractures accompanied by ankle joint subluxation and summarized the successful experience of collaboration by a multidisciplinary team(MDT).In terms of nursing,personalized body position management was implemented to relieve inferior vena cava com-pression;a phased analgesic strategy combining nerve block with drugs safe for the fetus was adopted;continuous electronic fetal heart rate and uterine contraction monitoring were carried out to ensure fetal stability during surgery;VTE prevention was strengthened by combining intermittent pneumatic com-pression devices with low-molecular-weight heparin;nutritional support and psychological counseling were provided.No complications such as infection,thrombosis,or fetal distress occurred after surgery.The Patient's ankle Kofoed score reached 88 points three months after surgery,indicating good func-tional recovery.Finally,the patient delivered a healthy male infant at full term,with a good Apgar score,and both the mother and the infant were safe.The case indicates that refined perioperative nursing combined with multidisciplinary collaboration can effectively reduce risks and improve the clinical outcomes of pregnant patients with fractures.

Purpose To investigate the expression of Versican(VCAN)and thrombospondin 2(THBS2)and their relationship with cancer-associated fibroblast(CAFs)and clinicopathological significance in papillary thyroid car-cinoma(PTC).Methods Bioinformatics analyses were performed using PTC single-cell sequencing data from the GEO and TCGA database.Weighted correlation network analysis identified CAFs-related genes,and enrichment analy-sis highlighted pivotal genes associated with CAFs;the expression of VCAN,THBS2,and α-SMA in 130 PTC tissue samples were detected by immunohistochemistry EnVision method.Masson staining evaluated tumor stromal fibrosis.Relationships between these markers,clinicopathological parameters,and CAF proliferation were analyzed.Results Bioinformatics analysis identified VCAN and THBS2 as core genes significantly associated with CAFs,and extracellular matrix-related pathways.The proliferation rate of CAFs in PTC was 83.1％(108/130),with positivity rate of 96.9％(126/130)for VCAN and 75.4％(98/130)for THBS2.The median mesenchymal fibrosis index was 32.4(inter-quartile range:22.7-50.0).High CAF proliferation correlated positively with lymph node metastasis(P＜0.001),higher TNM stage(P＜0.05),and specific histologic subtypes of PTC.Similarly,VCAN expression,THBS2 expres-sion,and the degree of PTC stromal fibrosis were positively correlated with lymph node metastasis(P＜0.001,P＜0.05,and P＜0.001,respectively).Both THBS2 expression and the degree of PTC stromal fibrosis correlated with the histologic subtype of PTC.The percentage of tumor mesenchymal α-SMA-positive cells strongly correlated with the im-mune response score(IRS)of VCAN and THBS2(rs=0.713,P＜0.001;rs=0.646,P＜0.001).Additionally,the percentage of Masson-stained area was positively correlated with the percentage of tumor mesenchymal α-SMA-posi-tive cells,and the IRS of VCAN and THBS2(rs=0.892,P＜0.001;rs=0.729,P＜0.001;rs=0.616,P＜0.001).Conclusion VCAN and THBS2 serve as potential markers for assessing invasiveness and lymph node metas-tasis of PTC.Their strong association with CAFs provides a basis for further investigation of the malignant biological be-havior of PTC.

AIM:This study aims to investigate the effects of aerobic exercise on hypothalamic autophagy and central leptin resistance in obese mice,and to explore the potential mechanisms.METHODS:Forty male C57BL/6J mice,aged 7 to 8 weeks,were randomly assigned to 5 groups:normal control(CON)group,high-fat diet(HFD)group,HFD+exercise(HFD+Exe)group,HFD+phosphate-buffered saline(PBS)group,and HFD+rilmenidine(autophagy ago-nist)group,with 8 mice in each group.Additionally,twelve fibronectin type Ⅲ domain-containing protein 5(Fndc5)gene(encoding irisin precursor protein)knockout(Fndc5 KO)mice were randomly allocated to Fndc5 KO+HFD group and Fndc5 KO+HFD+Exe group,with 6 mice in each group.All mice were fed for 28 weeks.The mice in CON group re-ceived a normal diet,while those in the remaining groups were provided with an HFD.The mice in HFD+Exe and Fndc5 KO+HFD+Exe groups engaged in aerobic treadmill exercise while continuing an HFD from weeks 17 to 28.The mice in HFD+PBS group received intraperitoneal injections of PBS as a control,while those in HFD+rilmenidine group received in-traperitoneal injections of rilmenidine(10 mg?kg-1?d-1),4 times a week over a total duration of 12 weeks(weeks 17 to 28).Following the intervention,serum metabolite levels,as well as concentrations of leptin and irisin,were quantified by ELISA.Morphological alterations in the liver and white adipose tissues were evaluated through oil red O staining and he-matoxylin-eosin(HE)staining.Western blot was utilized to assess the hypothalamic protein levels of autophagy markers,autophagy-related protein 7(ATG7),beclin-1,microtubule-associated protein 1 light chain 3(LC3)and p62,and leptin resistance markers,suppressor of cytokine signaling 3(SOCS3)and protein tyrosine phosphatase 1B(PTP1B).RE-SULTS:Observations of mouse phenotypes indicated that HFD feeding significantly increased body weight,blood lipid content and serum leptin level(P<0.05).The results of HE and oil red O staining demonstrated that HFD feeding marked-ly promoted lipid accumulation in the liver and caused ballooning of white adipocytes.Western blot analyses revealed that HFD feeding significantly down-regulated the protein levels of ATG7,beclin-1 and LC3-Ⅱ/LC3-I,but up-regulated the pro-tein level of p62(P<0.05),thus reducing cellular autophagy capacity.Furthermore,HFD feeding elevated the protein levels of leptin resistance markers SOCS3 and PTP1B(P<0.05).Aerobic exercise and autophagy agonist were found to partially reverse these changes,enhancing cellular autophagy capacity and alleviating leptin resistance.However,these effects were diminished after knockout of Fndc5 gene,further substantiating the role of irisin in exercise-mediated en-hancement of cellular autophagy and attenuation of leptin resistance.CONCLUSION:Aerobic exercise alleviates hypo-thalamic autophagy defect and central leptin resistance in obese mice,which may be associated with exercise-induced irisin.

Purpose To investigate the expression of Versican(VCAN)and thrombospondin 2(THBS2)and their relationship with cancer-associated fibroblast(CAFs)and clinicopathological significance in papillary thyroid car-cinoma(PTC).Methods Bioinformatics analyses were performed using PTC single-cell sequencing data from the GEO and TCGA database.Weighted correlation network analysis identified CAFs-related genes,and enrichment analy-sis highlighted pivotal genes associated with CAFs;the expression of VCAN,THBS2,and α-SMA in 130 PTC tissue samples were detected by immunohistochemistry EnVision method.Masson staining evaluated tumor stromal fibrosis.Relationships between these markers,clinicopathological parameters,and CAF proliferation were analyzed.Results Bioinformatics analysis identified VCAN and THBS2 as core genes significantly associated with CAFs,and extracellular matrix-related pathways.The proliferation rate of CAFs in PTC was 83.1％(108/130),with positivity rate of 96.9％(126/130)for VCAN and 75.4％(98/130)for THBS2.The median mesenchymal fibrosis index was 32.4(inter-quartile range:22.7-50.0).High CAF proliferation correlated positively with lymph node metastasis(P＜0.001),higher TNM stage(P＜0.05),and specific histologic subtypes of PTC.Similarly,VCAN expression,THBS2 expres-sion,and the degree of PTC stromal fibrosis were positively correlated with lymph node metastasis(P＜0.001,P＜0.05,and P＜0.001,respectively).Both THBS2 expression and the degree of PTC stromal fibrosis correlated with the histologic subtype of PTC.The percentage of tumor mesenchymal α-SMA-positive cells strongly correlated with the im-mune response score(IRS)of VCAN and THBS2(rs=0.713,P＜0.001;rs=0.646,P＜0.001).Additionally,the percentage of Masson-stained area was positively correlated with the percentage of tumor mesenchymal α-SMA-posi-tive cells,and the IRS of VCAN and THBS2(rs=0.892,P＜0.001;rs=0.729,P＜0.001;rs=0.616,P＜0.001).Conclusion VCAN and THBS2 serve as potential markers for assessing invasiveness and lymph node metas-tasis of PTC.Their strong association with CAFs provides a basis for further investigation of the malignant biological be-havior of PTC.

Objective To explore the pain catastrophizing (PC) level of pain in patients with multiple fractures and its influencing factors. Methods A convenience sampling method was used to investigate 156 patients with multiple fractures in the orthopedic trauma department of the First Affiliated Hospital of Nanjing Medical University. The questionnaire included a general information survey, a Digital Pain Rating Scale, PC scale, Positive and Negative Emotion Scale, and Social Rating Scale. Results The average PC score of patients with multiple fractures was (23.22±12.05), with 27 patients (17.20%) reaching the PC level. The average score of the Digital Pain Rating Scale was (6.30±1.49), the score of the Positive Emotion Scale was (27.92±6.06), the score of the Negative Emotion Scale was (23.18±7.00), and the total score of the Social Rating Scale was (27.90±4.61). The results of multiple linear regression analysis showed that pain score, negative emotion level, and social support level had predictive effects in PC among patients with multiple fractures. Conclusion The incidence of PC among patients with multiple fractures is at a moderate to high level. Patients with high pain scores, high negative emotion scores, and low social support are more likely to develop PC.

Objective:To compare the fertilization rate, embryonic developmental potential, and clinical outcomes following the applications of A23187 and Ionomycin.Methods:A total of 65 patients whose oocytes were exposed to either the A23187 or Ionomycin for artificial oocyte activation (AOA) due to total failed fertilization/lower fertilization rate in the previous intracytoplasmic sperm injection (ICSI) cycles or severe oligo-astheno-teratozoospermia at Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University from May 2010 to December 2019 were enrolled in this retrospective cohort study. All patients were categorized into two groups: A23187-AOA group and Ionomycin-AOA group. And each group was divided into two subgroups according to sperm origin (ejaculated or testicular sperm). The fertilization rate, embryo development potential and clinical outcome were compared between the two groups.Results:The two pronuclei (2PN) fertilization rate [55.0% (116/211) vs. 43.3% (135/312), P=0.008], 2PN cleavage rate [97.4% (113/116) vs. 90.4% (122/135), P=0.023] and blastocyst formation rate [69.1% (38/55) vs. 45.2% (14/31), P=0.029] in the Ionomycin-AOA group were significantly higher than those in the A23187-AOA group. In the ejaculated spermatozoa subgroup, the 2PN cleavage rate [97.1% (68/70) vs. 85.8% (91/106), P=0.013] and the rate of day 3 (D3) transferable embryos [92.6% (63/68) vs. 73.6% (67/91), P=0.002] in the Ionomycin-AOA group were higher than those in the A23187-AOA group; in the testicular spermatozoa subgroup, the 2PN fertilization rate [55.4% (46/83) vs. 37.7% (29/77), P=0.024], the blastocyst formation rate [93.3% (14/15) vs. 20.0% (1/5), P=0.005], the implantation rate [38.9% (7/18) vs. 5.6% (1/18), P=0.041] and the cumulative clinical pregnancy rate [66.7% (6/9) vs. 10.0% (1/10), P=0.019] in the Ionomycin-AOA group were higher than those in the A23187-AOA group. A total of 20 healthy neonates were delivered in 65 patients. None of the congenital anomalies (birth defects) was found in fetuses after AOA. Conclusion:Ionomycin may be superior to A23187 for improving fertilization rate and embryonic developmental potential. And compared with A23187, Ionomycin may be a more efficient means to benefit the patients with testicular-origin severe oligo-astheno-teratozoospermia.

Objective:To compare the fertilization rate, embryonic developmental potential, and clinical outcomes following the applications of A23187 and Ionomycin.Methods:A total of 65 patients whose oocytes were exposed to either the A23187 or Ionomycin for artificial oocyte activation (AOA) due to total failed fertilization/lower fertilization rate in the previous intracytoplasmic sperm injection (ICSI) cycles or severe oligo-astheno-teratozoospermia at Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University from May 2010 to December 2019 were enrolled in this retrospective cohort study. All patients were categorized into two groups: A23187-AOA group and Ionomycin-AOA group. And each group was divided into two subgroups according to sperm origin (ejaculated or testicular sperm). The fertilization rate, embryo development potential and clinical outcome were compared between the two groups.Results:The two pronuclei (2PN) fertilization rate [55.0% (116/211) vs. 43.3% (135/312), P=0.008], 2PN cleavage rate [97.4% (113/116) vs. 90.4% (122/135), P=0.023] and blastocyst formation rate [69.1% (38/55) vs. 45.2% (14/31), P=0.029] in the Ionomycin-AOA group were significantly higher than those in the A23187-AOA group. In the ejaculated spermatozoa subgroup, the 2PN cleavage rate [97.1% (68/70) vs. 85.8% (91/106), P=0.013] and the rate of day 3 (D3) transferable embryos [92.6% (63/68) vs. 73.6% (67/91), P=0.002] in the Ionomycin-AOA group were higher than those in the A23187-AOA group; in the testicular spermatozoa subgroup, the 2PN fertilization rate [55.4% (46/83) vs. 37.7% (29/77), P=0.024], the blastocyst formation rate [93.3% (14/15) vs. 20.0% (1/5), P=0.005], the implantation rate [38.9% (7/18) vs. 5.6% (1/18), P=0.041] and the cumulative clinical pregnancy rate [66.7% (6/9) vs. 10.0% (1/10), P=0.019] in the Ionomycin-AOA group were higher than those in the A23187-AOA group. A total of 20 healthy neonates were delivered in 65 patients. None of the congenital anomalies (birth defects) was found in fetuses after AOA. Conclusion:Ionomycin may be superior to A23187 for improving fertilization rate and embryonic developmental potential. And compared with A23187, Ionomycin may be a more efficient means to benefit the patients with testicular-origin severe oligo-astheno-teratozoospermia.

Objective To study the effect of clopidogrel on different CYP2C19 genotypes and platelet reactivity in acute cerebral infarction patients with antiplatelet aggregation.Methods Four hundred and seventy-four cases of cerebral infarction patients in Beijing Tiantan Hospital Affiliated to Capital Medical University from April 2015 to April 2016 were collected.CYP2C19 genotype was determined,and the genotype was divided into the wild type group,the heterozygous type group and the mutant homozygous group.Platelet aggregation inhibition rate(ADP%) and platelet reactivity index induced by ADP were detected.Patients were divided into clopidogrel resistance group(group CR) and non resistant group according to whether ADP% was less than 30.SPSS 16.0 statistical software was used for statistical analysis,the comparison between groups using independent samples t test,chi square test and multivariate analysis using Logistic regression analysis,when P<0.05 difference was statistically significant.Results Among the 474 patients,204 cases(43.04%) were divided into wild-type group,and 204(43.04%) and 66(13.92%) were divided into the mutant heterozygous group and mutant homozygous group.In Chi square test analysis,clopidogrel resistance group and non resistance group CYP2C19 genotype distribution was significantly different(χ2=6.658,P=0.036).CR group angle(α) values((68.87±5.47)°) and MA((66.77±6.25) mm) were higher than that of CS group ((66.55±6.05)° and (63.30±5.66) mm,t=2.199,3.387,P=0.029,0.001).The multivariate logistic regression analysis showed that OR of angle level was 1.028,95%CI was 0.929-1.137 (P=0.595);OR of Ma level was 1.561,95%CI was 0.785-0.970 (P=0.012).Conclusion The effect of clopidogrel on platelet aggregation in patients with acute cerebral infarction is decreased by CYP2C19 gene mutation.CYP2C19 mutant allele is a risk factor for clopidogrel resistance.Angle (α) value and MA value are the risk factors for the diagnosis of CR in the patients with acute cerebral infarction,and the risk of clopidogrel resistance increased when the patients′ Angle (α) value and the value of MA increased.MA value as a predictor of CR and the screening tool has a certain value.