BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

OBJECTIVE To analyze the clinical characteristics and influential factors of drug-induced liver injury （DILI） in children caused by intravenous azithromycin. METHODS Clinical data of 157 DILI pediatric cases caused by intravenous azithromycin， reported by the Hengshui Adverse Drug Reaction Monitoring Center from January 2015 to January 2025， were collected as the observation group. Clinical data of pediatric patients who received intravenous azithromycin but did not develop DILI during the same period at Hengshui People’s Hospital were collected in a 1∶1 ratio to serve as the control group. The clinical classification， severity and prognosis of DILI in pediatric patients from the observation group were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for DILI in children caused by intravenous azithromycin. RESULTS Among 157 DILI cases， 92 cases （58.60%） had hepatocellular injury-type， 51 cases （32.48%） had cholestatic-type， and 14 cases （8.92%） had mixed-type. DILI severity was grade 1 in 117 cases （74.52%）， grade 2 in 33 cases （21.02%）， and grade 3 in 7 cases （4.46%）. Liver function had all recovered after stopping medication and symptomatic treatment. Combined with acetaminophen [OR＝3.769， 95%CI （1.615， 8.235）， P＝0.021]， daily dose of azithromycin＞10 mg/kg [OR＝ 2.237， 95%CI （1.075， 4.655）， P＝0.034] were independent risk factors for DILI in children caused by intravenous azithromycin. CONCLUSIONS Hepatocellular injury-type and cholestatic-type are relatively common in children with DILI caused by intravenous azithromycin， with mild severity being predominant and showing a favorable prognosis. Combination with acetaminophen and daily dose＞10 mg/kg are independent risk factors for azithromycin-induced DILI in children.

Objective To explore the effect of individualized positive end expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy for elderly patients.Methods A total of 64 patients underwent elective laparoscopic radical gastrectomy for gastric cancer in the Second Affiliated Hospital of Anhui Medical University were selected.According to the random number table method,patients were divided into the driving the pressure guided individualized positive end-expiratory pressure(PEEP)group(experimental group)and the fixed PEEP group(control group),32 cases in each group.In the control group,PEEP = 5 cmH2O.In the experimental group,PEEP titration was performed according to the increasing method,and the PEEP corresponding to the lowest driving pressure was selected until extubation.Peak airway pressure(Ppeak),plateau airway pressure(Pplat)and PEEP were recorded at 5 min after intubation(T1),immediately after PEEP titration(T2),1 h after operation(T3),2 h after operation(T4),and 10 min after pneumoperitoneum release(T5).Driving pressure(ΔP)and lung dynamic compliance(Cdyn)were calculated.Arterial blood was collected at T1-5 for blood gas analysis,arterial partial pressure of oxygen(PaO2)was recorded,and oxygenation index(OI)was calculated.The occurrence of pulmonary complications(PPCs)within 7 days after operation was recorded.Modified clinical pulmonary infection score(mCPIS)was recorded on the second day after operation.The pulmonary function was evaluated before operation,1 day,3 days and 5 days after operation.Results Compared with T1,Ppeak,Pplat and ΔP were increased and Cdyn was decreased at T2-5,while OI was decreased at T4 in control group(P＜0.05).Compared with the control group,Ppeak,Pplat and Cdyn in the experimental group were increased at T2-5,ΔP was decreased,and OI was increased at T3-5(P＜0.05).Compared with the preoperative results,FVC at 1,3 and 5 days after surgery was decreased,and FEV1 and maximum expiratory flow(PEF)were decreased 1 and 3 days after surgery in the experimental groups(P＜0.05).Compared with the control group,FVC,FEV1 and PEF were higher 1 day after operation in the experimental group(P＜0.05).Compared with the preoperative results,mCPIS scores of the two groups were higher on the second day after surgery(P＜0.05).Compared with the control group,the mCPIS score was lower on day 2 after surgery in the experimental group(P＜0.05).The incidence of PPCs within 7 days after surgery was lower in the experimental group than that in the control group(15.6%vs.40.6%).Conclusion Individualized PEEP guided by drive pressure can improve lung compliance,reduce drive pressure,improve oxygenation function and early postoperative lung function,reduce the incidence of postoperative lung complications,and has a certain lung protection effect.

Burkitt lymphoma is a highly aggressive B-cell lymphoma and the fastest proliferating human malignant tumor.If the disease is found in the early stage,the patient could have a high possibility to be cured successfully,whereas the prognosis is poor in the late stage.Burkitt lymphoma can occur in children and adults,and it is categorized as local(Africa),sporadic,and immunodeficiency associated type.Sporadic Burkitt lymphoma mainly affects children and ado-lescents,and the most common initial sites are abdominal organs and lymph nodes.Sporadic Burkitt lymphoma manifested by initial oral and maxillofacial lesions is rela-tively rare.Here,a case of pediatric sporadic Burkitt lym-phoma,with oral and maxillofacial lesions as the first symptoms,was reported.The patient was treated in the Department of Periodontology,Shandong University School and Hospital of Stomatology.After timely checkup was pro-vided,the patient was transferred to another hospital and had good results.In this article,an incidence of Burkitt lympho-ma,with oral and maxillofacial lesions as the first symptom,was reviewed to provide reference for oral clinicians to achieve early diagnosis and treatment of patients with Burkitt lymphoma with oral diseases and improve the success rate of treatment.

OBJECTIVE To explore the mechanism of Compound lizard powder reducing cisplatin resistance in gastric cancer by regulating glycolytic activity based on phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. METHODS Human gastric cancer MKN45 and MKN45/DDP （cisplatin-resistant） cells were cultured in vitro and intervened with different mass concentrations of cisplatin （0.1， 0.2， 0.4， 0.8， 1.6， 3.2 μg/mL） to detect the survival rate， half inhibitory concentration （IC50） and drug resistance index. MKN45/DDP cells were inoculated subcutaneously in the right anterior axilla of nude mice to prepare a transplanted tumor model of gastric cancer. After successful modeling， they were randomly divided into model group， cisplatin group （0.002 g/kg）， Compound lizard powder group （2.8 g/kg） and combination group （the same dose as each single drug group）， with 8 nude mice in each group. Each administration group was given relevant solution， twice a week （cisplatin， i.p.） or twice a day （Compound lizard powder， i. g.）， for 4 consecutive weeks. During the experiment， the body weight of nude mice was monitored， and tumor volume and inhibitory rate of tumor were calculated. The levels of inflammatory factors （tumor necrosis factor- α， interleukin-6） in tumor tissue， the mRNA and protein expressions of multidrug resistance-associated protein 1 （MRP1）， P-glycoprotein （P-gp）， glucose transporter-1 （GLUT1） and lactate dehydrogenase A （LDHA）， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， hexokinase-2 （HK2） and pyruvate kinase M2 （PKM2） were all detected. RESULTS With the intervention of different concentrations of cisplatin， the survival rate of MKN45/DDP-resistant cells was significantly higher than that of MKN45 parent cells （P＜0.05）. IC50 value of MKN45/DDP and MKN45 cells were（1.052 0±0.221 9） and （0.372 1±0.238 0）μg/mL， and the drug resistant index was 2.827. Compared with the model group， cisplatin group， Compound lizard powder group and combination group all had certain inhibitory effects on the tumor growth in nude mice； the inhibitory rates of tumor increased significantly （P＜0.05）； the levels of inflammatory factors， the mRNA and protein expressions of MRP1， P-gp， GLUT1 and LDHA （except for cisplatin group）， the phosphorylation levels of PI3K and Akt protein （except for cisplatin group） as well as the protein expressions of HK2 and PKM2 were decreased significantly， while the combination group was significantly better than the cisplatin group （P＜0.05）. CONCLUSIONS Compound lizard powder may inhibit tumor growth in transplanted tumor model nude mice with gastric cancer-resistant cells by reducing the secretion of tumor-related inflammatory factors， inhibiting the expression of glycolysis， drug resistance-related proteins and genes， inhibiting the activation of the PI3K/Akt signaling pathway， thus having a certain effect of enhancing cisplatin efficacy and reversing drug resistance.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Ischemic stroke(IS)is a severe cerebrovascular disease that seriously endangers human health.Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine.In recent years,trimethylamine N-oxide(TMAO)as a gut microbiota metabolite has received widespread attention in cardiovascular diseases.Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis,atrial fibrillation,hypertension,and type 2 diabetes.TMAO exacerbates neurological damage in IS patients,increases the risk of IS recurrence,and is an independent predictor of post-stroke cognitive impairment(PSCI)in patients.Current research suggests that the mechanisms of TMAO action include endothelial dysfunction,promoting of foam cell formation,influence on cholesterol metabolism,and enhancement of platelet reactivity.Lowering plasma TMAO levels through the rational use of traditional Chinese medicine,dietary management,vitamins,and probiotics can prevent and treat IS.

Microgravity in space will lead to the decline of astronauts'motor sensation,which will affect the ability of balance maintenance and posture control.Which limits the ability of astronauts to quickly get out of danger in case of extravehicular activities or landing emergencies,and seriously affects the completion of space missions and endangers the safety of astronauts.The current weightlessness countermeasure based on exercise can effectively alleviate the problems of skeletal muscle and cardiovascular system caused by weightlessness to a certain extent,but it cannot effectively prevent the motor sensory dysfunction after space flight.Therefore,new weightlessness countermeasures of special physical conditioning are needed to attenuate the decline of human balance control ability after long-term space flight.By reviewing the previous research results of space flight and simulated weightlessness experiments,this paper systematically analyzes the influencing factors of human body balance control,compares the balance control promotion schemes of special physical conditioning in the field of sports,and puts forward the potential protection strategies for weightlessness environment based on the integration of sports and medicine.The feedback regulation of muscle tension,tactile and proprioceptive play an important role in human posture balance and motion control.The unloading of human gravity load in space weightlessness environment will greatly reduce the input-output feedback regulation activity of the above senses which may lead to balance dysfunction.The post-flight balance control dysfunction may be improved by special physical conditioning,such as loading of z-axial load,enhancement of tactile feedback and proprioceptive response based on unstable mechanical stress stimulation during spaceflight.