Objective To explore the related functional mechanism of Xihuang pill containing serum inter-vention in breast cancer cells based on microRNA(miR)21-5p targeting FAM13A gene.Methods Bioinfor-matics websites was used to predict potential miRNAs of FAM13A gene,double luciferase reporter experi-ments were conducted to verify the binding site relationship between FAM13A and predicted miRNAs.The Xihuang pill containing serum was prepared,and human breast cancer MDA-MB-231 cells were cultured.The proliferation of MDA-MB-231 cells was interfered by the Xihuang pill containing serum with different dilution ratios by CCK-8 test,and the best dilution ratio concentration of Xihuang pill containing serum to inhibit the proliferation of breast cancer cells was selected.Real time fluorescence quantitative PCR(RT-qPCR)was ap-plied to detect the relative expression levels of FAM13A mRNA,as well as the relative expression levels of miR21-5p,in MDA-MB-231 cells after intervention with Xihuang pill containing serum.Cell proliferation(Edu)assay and cell apoptosis detection(TUNEL)assay were used to detect the effects of Xihuang pill con-taining serum intervention on cell proliferation and apoptosis function in MDA-MB-231 cells.The siRNA lentiviral transfection on MDA-MB-231 cells was performed to knock down the FAM13A gene,and Edu assay and TUNEL assay were used to detect changes in proliferation and apoptosis ability of MDA-MB-231 cells af-ter lentiviral transfection.The expression level of miR21-5p in MDA-MB-231 cells after FAM13A gene knock-out was detected by RT-qPCR technology.Results Target Scan online website predicted the potential miR-21-5p binding sequence in the 3'UTR of FAM13A mRNA,and dual luciferase reporter assay confirmed the in-teraction between miR-21-5p and FAM13A.After intervention of MDA-MB-231 cells with Xihuang pill drug containing serum,RT-qPCR results showed that compared with the control group(NC group),the Xihuang pill drug containing serum group(XHW group)downregulated the expression levels of FAM13A mRNA(P＜0.05),and upregulated the expression level of miR21-5p(P＜0.05).Compared with the NC group,the XWH group showed reduced cell proliferation ability and promoted cell apoptosis.(P＜0.05).After silencing the FAM13A gene in MDA-MB-231 cells,compared with the control group(shCtrl group),the shFAM13A group showed a significant decrease in cell proliferation ability and promoted cell apoptosis.The RT-qPCR re-sults showed that compared with the shCtrl group,the expression level of miR21-5p was significantly upregu-lated in the shFAM13A group(P＜0.05).Conclusion Xihuang pill could participate in the anti-tumor treat-ment of breast cancer by regulating miR21-5p to affect the expression level of FAM13A gene.

Objective To establish a stable and reproducible animal model of abdominal intestinal firearm penetrating injury in a cold high-altitude environment.Methods Twenty landrace pigs were randomly and equally assigned to a low-altitude normal temperature(LN)group and a high-altitude cold(HC)group.The HC group was placed in a cold environment at high altitudes,and the LN group was placed in a normal-temperature environment at low altitudes.They were raised for 48 hours respectively.After anesthesia,they were suspended on the shooting range,and the right lower abdomen of the experimental pigs was shot with a gun.After injury,they were simply bandaged and transported back to the laboratory for observation in the normal temperature environment of the low altitudes.The vital signs and injuries at 0,2,4,8,12 and 24 h and 24 h survival rates of experimental pigs were compared.Laparotomy was immediately performed on the dead pigs and the experimental pigs still alive at 24 h to explore the injuries and observe the pathology of the small intestine and colon.Results The 24 h survival rate of the HC group was 70％,with no statistically significant difference compared to the LN group's 90％(P＞0.05).After the injury,the body temperature of both groups gradually increased.The body temperature of the HC group was significantly higher than the LN group at 0,2,4 and 8 h time points(P＜0.001),and the LN group exceeded the HC group at 24 h(P＜0.05).Both groups showed an initial increase followed by a decrease in heart rate,with the HC group significantly higher than the LN group only at 0 h(P＜0.01),and no statistically significant differences were observed at other time points(P＞0.05).Both groups showed an early increase and later decrease in respiratory rate,with the HC group higher than the LN group at 0,4,8,12 and 24 h(P＜0.05 or P＜0.001).There was no statistically significant difference(P＞0.05)between the HC group and the LN group in small intestine rupture,small intestine contusion,mesenteric injury,colon rupture and wound diameter.The pathology of the small intestine and colon in the HC group showed extensive necrosis and shedding of the mucosa layer,severe congestion and edema of the submucosa,and extensive lymphocyte infiltration.The LN group also showed similar symptoms but to a lesser extent.Conclusion This study established a pig model of abdominal firearm intestinal perforation injury in a cold environment at high-altitudes.The model has strong operability and stable damage,which can provide a reference for subsequent research.

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy. METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species. RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01). CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.

Background Dibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. Objective To investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. Methods Thirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg⁻¹ DBP exposure group (OVA+DBP), and OVA+40 mg·kg⁻¹ DBP+50 mg·kg⁻¹ 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg⁻¹ DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. Results Compared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P<0.01), the Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) cytokines in BALF (P<0.01), and the expression levels of endoplasmic reticulum stress-related proteins IRE1α, PERK and ATF-6 (P<0.01). In addition, after the 4-PBA treatment, it was found that compared with the OVA+DBP group, the expression levels of endoplasmic reticulum stress-related proteins (IRE1α, PERK and ATF-6) were down-regulated in the OVA+DBP+4-PBA group (P<0.01), the levels of cytokines (IL-4, IL-5, IL-13, and IL-17A) in BALF and T-IgE and OVA-IgE in serum were decreased (P<0.01), and airway remodeling and mucous hyperplasia were significantly alleviated. Conclusion Long-term exposure to DBP could aggravate allergic asthma by activating the endoplasmic reticulum stress pathway. This worsening effect is accompanied by the increase of immunoglobulin IgE levels and the release of Th2 and Th17 cytokines, which in turn leads to lung histopathological changes that affect lung function.

Background With the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro. Objective To explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life. Methods Twelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg⁻¹·d⁻¹) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot. Results Compared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05). Conclusion Early-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice.

Objective To explore the associations between risk factors for cardiovascular disease and breast cancer. Methods A total of 300 patients with breast cancer and 300 with benign breast diseases diagnosed by postoperative pathology were included in the Department of Breast Surgery, Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2023 to June 2023. The main cardiovascular risk factors in patients between the two groups were compared. Stratification was performed according to menstrual status, and the main cardiovascular risk factors in patients with different menstrual status between the two groups were compared. The logistic regression correlation analysis was used to analyze the risk factors related to cardiovascular disease for breast cancer. Results There were statistically significant differences in clinical data and laboratory indicators between the two groups (P＜0.01) . Multivariate logistic regression analysis showed that age (OR=1.03, P=0.029), triglyceride (TG; OR=1.94, P=0.025), C-reactive protein (CRP; OR=2.73, P＜0.001), D-dimer (OR=61.19, P＜0.001), and homocysteine (Hcy; OR=2.10, P＜0.001) were independently associated with breast cancer. The stratified analysis showed age, TG, CRP, D-dimer, and Hcy were independently associated with breast cancer in both premenopausal and postmenopausal patients (P＜0.05). Conclusions Among risk factors for cardiovascular disease, advanced age, increased TG, CRP, D-dimer, and Hcy might increase breast cancer risk, which are helpful of screening high-risk individuals for breast cancer.

Objective To observe the effects of electroacupuncture on the motor function and mitochondrial dynamics of skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in improving the motor dysfunction of Alzheimer disease(AD)from the perspective of mitochondrial dynamics.Methods Totally 18 SAMP8 mice were divided into model group and electroacupuncture group,with 9 mice in each group,and the SAMR1 mice with the same age were set as control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,and electroacupuncture was performed daily for 20 min,8 d as a course of treatment.Each course of treatment was separated by 2 d,for a total of 3 courses of treatment.The model group and the control group were not intervened.The motor function of mice was tested by grip strength test,suspension test,hind limb extension test and Morris water maze experiment.The morphology and structure of gastrocnemius were observed by HE staining,ATP content in gastrocnemius was determined by colorimetry,the mRNA expression of optic atrophy 1(OPA1),mitofusin 2(MFN2)and dynamin-related protein 1(DRP1)in gastrocnemius were detected by real-time quantitative PCR,the expressions of OPA1,MFN2 and DRP1 in gastrocnemius were detected by Western blot.Results Compared with the control group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment of mice in model group significantly decreased(P<0.01);the arrangement of fibers in the gastrocnemius muscle tissue was disordered,the gaps become wider,and the distribution of nuclei was uneven;the ATP content in the gastrocnemius muscle tissue was significantly decreased(P<0.01),the mRNA and protein expressions of OPA1 and MFN2 were significantly decreased(P<0.01),and the expression of DRP1 mRNA and protein significantly increased(P<0.01).Compared with the model group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment in electroacupuncture group significantly increased(P<0.01);the arrangement of gastrocnemius muscle tissue was relatively neat,the gaps become narrower,and the distribution of nuclei was more uniform;the ATP content in gastrocnemius muscle tissue significantly increased(P<0.01),while the mRNA and protein expressions of OPA1 and MFN2 significantly increased(P<0.05,P<0.01),the expression of DRP1 mRNA and protein significantly decreased(P<0.01).Conclusion Electroacupuncture can improve the skeletal muscle morphological structure and motor dysfunction of SAMP8 mice,and the mechanism may be related to the correction of skeletal muscle mitochondrial dynamic imbalance and the increase of skeletal muscle ATP content.

Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy. METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species. RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01). CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy. METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species. RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01). CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.