BACKGROUND:The liver,as the main target organ for arsenic toxicity,has become the focus of studies related to the mechanism of action of arsenic toxicity.OBJECTIVE:To investigate the effects of sodium arsenite(NaAsO2)on lipid metabolism,cell proliferation,apoptosis,and expression of related regulatory factors in human normal hepatocytes.METHODS:MIHA normal human hepatocyte cell lines were exposed to 0,10,20,and 30 μmol/L NaAsO2 for 48 hours.Cell morphology changes were observed by light microscopy.Cell viability was detected by CCK-8 assay.The cell serum total cholesterol,triacylglycerol,and total bile acids were detected by single-agent COD-PAP assay,single-agent GPO-PAP assay,and enzyme microplate assay.The intracellular lipid content was detected by oil red O staining.Cell proliferation was detected by Edu-488 infiltration.Cell cycle and apoptosis were detected by PI staining and Annexin V-FITC/PI dual-labeling combined with flow cytometry.The mRNA and protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor were detected by real-time fluorescence quantitative PCR and western blot assay,respectively.RESULTS AND CONCLUSION:(1)Compared with the control group(0 μmol/L NaAsO2),with the increase of NaAsO2 concentration:MIHA cell viability decreased gradually.The content of total cholesterol and triacylglycerol in cell supernatant increased gradually,while the contents of total bile acids decreased gradually.The content of intracellular lipid increased gradually.The proportion of cells stagnating in S phase and G2/M phase gradually increased,and the apoptosis rate gradually increased.The expression level of hepatocyte nuclear factor 4 alpha mRNA did not show significant changes,while cholesterol 7α-hydroxylase and farnesoid X receptor mRNA expression levels decreased.The protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor decreased gradually.(2)NaAsO2 has cytotoxicity,significantly reduces MIHA cell viability,induces cell steatosis,inhibits cell proliferation,and induces cell apoptosis.NaAsO2 down-regulates hepatocyte nuclear factor 4 alpha protein expression and the transcription and expression of cholesterol 7α-hydroxylase and farnesoid X receptor,which further induces lipid metabolism disorders in hepatocytes.

Objective To investigate CBX2 and TIM3 in salivary adenoid cystic carcinoma(SACC)tissue and their relationship with clinical pathological features and prognosis.Methods 80 patients with SACC who underwent surgical treatment in the First Affiliated Hospital of Hebei North University from January 2016 to January 2020 were selected.Immunohistochemistry was used to measure CBX2 and TIM3 in tissues.The relationship between CBX2 and TIM3 in SACC tissue and prognosis was discussed though Kaplan-Meier method.The factors influencing the prognosis of SACC were discussed using multivariate Cox regression.Results The positive rates of CBX2 and TIM3 in SACC tissues were clearly higher than those in normal glandular tissues adjacent to cancer(χ2=11.237,8.229,P<0.05).The CBX2 and TIM3 were associated with nerve invasion and distant metastasis(P<0.05).After a 5-year follow-up,26 cases died and 54 cases survived,with an overall 5-year survival rate of 67.50%(54/80).The death group had higher positive rates of CBX2 and TIM3 in SACC tissues than the survival group(P<0.05).Patients with positive CBX2 and TIM3 in SACC tissues had clearly lower 5-year survival rate than patients with negative CBX2 and TIM3(Log Rank χ2=6.564,5.197,P<0.05).CBX2,TIM3 positivity,nerve invasion,and distant metastasis were risk factors affecting prognosis(P<0.05).Conclusion The positive expression of CBX2 and TIM3 in SACC tissues is closely related to the clinical pathological features and prognosis of patients.

Objective To investigate CBX2 and TIM3 in salivary adenoid cystic carcinoma(SACC)tissue and their relationship with clinical pathological features and prognosis.Methods 80 patients with SACC who underwent surgical treatment in the First Affiliated Hospital of Hebei North University from January 2016 to January 2020 were selected.Immunohistochemistry was used to measure CBX2 and TIM3 in tissues.The relationship between CBX2 and TIM3 in SACC tissue and prognosis was discussed though Kaplan-Meier method.The factors influencing the prognosis of SACC were discussed using multivariate Cox regression.Results The positive rates of CBX2 and TIM3 in SACC tissues were clearly higher than those in normal glandular tissues adjacent to cancer(χ2=11.237,8.229,P<0.05).The CBX2 and TIM3 were associated with nerve invasion and distant metastasis(P<0.05).After a 5-year follow-up,26 cases died and 54 cases survived,with an overall 5-year survival rate of 67.50%(54/80).The death group had higher positive rates of CBX2 and TIM3 in SACC tissues than the survival group(P<0.05).Patients with positive CBX2 and TIM3 in SACC tissues had clearly lower 5-year survival rate than patients with negative CBX2 and TIM3(Log Rank χ2=6.564,5.197,P<0.05).CBX2,TIM3 positivity,nerve invasion,and distant metastasis were risk factors affecting prognosis(P<0.05).Conclusion The positive expression of CBX2 and TIM3 in SACC tissues is closely related to the clinical pathological features and prognosis of patients.

BACKGROUND:The liver,as the main target organ for arsenic toxicity,has become the focus of studies related to the mechanism of action of arsenic toxicity.OBJECTIVE:To investigate the effects of sodium arsenite(NaAsO2)on lipid metabolism,cell proliferation,apoptosis,and expression of related regulatory factors in human normal hepatocytes.METHODS:MIHA normal human hepatocyte cell lines were exposed to 0,10,20,and 30 μmol/L NaAsO2 for 48 hours.Cell morphology changes were observed by light microscopy.Cell viability was detected by CCK-8 assay.The cell serum total cholesterol,triacylglycerol,and total bile acids were detected by single-agent COD-PAP assay,single-agent GPO-PAP assay,and enzyme microplate assay.The intracellular lipid content was detected by oil red O staining.Cell proliferation was detected by Edu-488 infiltration.Cell cycle and apoptosis were detected by PI staining and Annexin V-FITC/PI dual-labeling combined with flow cytometry.The mRNA and protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor were detected by real-time fluorescence quantitative PCR and western blot assay,respectively.RESULTS AND CONCLUSION:(1)Compared with the control group(0 μmol/L NaAsO2),with the increase of NaAsO2 concentration:MIHA cell viability decreased gradually.The content of total cholesterol and triacylglycerol in cell supernatant increased gradually,while the contents of total bile acids decreased gradually.The content of intracellular lipid increased gradually.The proportion of cells stagnating in S phase and G2/M phase gradually increased,and the apoptosis rate gradually increased.The expression level of hepatocyte nuclear factor 4 alpha mRNA did not show significant changes,while cholesterol 7α-hydroxylase and farnesoid X receptor mRNA expression levels decreased.The protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor decreased gradually.(2)NaAsO2 has cytotoxicity,significantly reduces MIHA cell viability,induces cell steatosis,inhibits cell proliferation,and induces cell apoptosis.NaAsO2 down-regulates hepatocyte nuclear factor 4 alpha protein expression and the transcription and expression of cholesterol 7α-hydroxylase and farnesoid X receptor,which further induces lipid metabolism disorders in hepatocytes.

ObjectiveTo determine the optimal dose of Dachengqi Decoction （大承气汤， DCQD） for the treatment of acute intestinal obstruction （AIO） through a randomized， double-blind， dosage parallel controlled， multi-center clinical trial， and to providee evidence support for the reasonable dosage of DCQD in clinical practice. MethodsBased on the commonly used clinical dose of DCQD， three different groups were set up， including low-dose group which used Dahuang （Radix et Rhizoma Rhei） 12 g， Houpo （Cortex Magnoliae Officinalis） 9 g， Zhishi （Fructus Aurantii Immaturus） 9 g， and Mangxiao （Natrii Sulfas） 4.5 g， medium-dose group using Dahuang 36 g， Houpo 27 g， Zhishi 27 g， Mangxiao 13.5 g， and high-dose group using Dahuang 60 g， Houp0 45 g， Zhishi 45 g and Mangxiao 22.5 g. Initially， 149 AIO patients with Yangming （阳明） bowel excess syndrome were randomly assigned to three groups using a stratified randomization method， and both the patients and the doctors were blinded. In addition to conventional western medicine treatment， each group was given 12 bags of granules made from the raw herbs of DCQD at different doses， taken orally or injected through a gastric catheter once every 6 hours， 3 bags each time， for 3 consecutive days. After treatment， the indicators of the three groups of patients with primary AIO and non-primary AIO were evaluated respectively， and the full analysis set （FAS） and per-protocol set （PPS） were used for analysis. The primary outcomes were the time to recover voluntary bowel movements and voluntary flatulence. The secondary outcomes were the ideal rate of spontaneous defecation and the ideal rate of spontaneous flatus. The occurrence of adverse events during the study was recorded and analyzed using the safety analysis set （SS）. ResultsA total of 91 patients with primary AIO and 58 patients with non-primary AIO were included in the FAS and SS analysis， while 80 primary AIO patients and 56 non-primary AIO patients were included in the PPS analysis. Both FAS and PPS analysis showed significant differences in the time to recover voluntary bowel movements and voluntary flatulence among primary AIO patients in different dose groups of DCQD （P＜0.01）， and the high- and medium-dose groups assumed less time than the low-dose group （P＜0.05）. There was no statistically significant difference in the ideal rate of spontaneous defecation and spontaneous flatus among the three groups （P＞0.05）. And consistent results were seen in the non-primary AIO patients among the three groups. Five adverse events occurred in primary AIO patients （3 in the low-dose group， 1 in the medium-dose group， and 1 in the high-dose group）， mainly manifested as abdominal distension and abdominal pain， and there was no statistically significant difference in the incidence of adverse events （P＞0.05）. No adverse events occurred in patients with non-primary AIO. ConclusionDCQD， as an effective treatment for patients with AIO， is commonly used at a medium dose for patients with primary AIO and at a high dose for patients with non-primary AIO. The therapeutic advantage is mainly reflected in the shorter time to recover spontaneous defecation and spontaneous flatulence and the improvement of intestinal function.

Objective:To explore the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) and serum trimethylamine oxide (TMAO) on in-hospital mortality events in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) upon admission.Methods:A retrospective collection of medical records of 103 AMICS patients admitted to the Shanxi Yingkang Life General Hospital from January 2018 to June 2023 was conducted. The patients were divided into a survival group ( n=78) and a death group ( n=25) based on whether they experienced in-hospital mortality events. Two groups of peripheral blood NLR, serum TMAO, baseline data, and other laboratory indicators were compared. A logistic regression model was used to analyze the risk factors for in-hospital mortality in AMICS patients and a prediction model was constructed. We established receiver operating characteristic (ROC) curves to evaluate the predictive efficacy of peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and predictive model indicators for in-hospital mortality events in AMICS patients. Results:The peripheral blood NLR and serum TMAO levels in the death group were significantly higher than those in the survival group (all P<0.05). The age of the death group was higher than that of the survival group, and the proportion of hypertension, alanine aminotransferase, creatinine, random blood glucose, proportion of patients who did not receive emergency percutaneous coronary intervention (PCI) treatment, peak cardiac troponin I, B-type natriuretic peptide, Gensini score of coronary artery disease, and C-reactive protein were all higher than those of the survival group. Systolic blood pressure and platelet count were lower than those of the survival group, heart rate and erythrocyte sedimentation rate were faster than those of the survival group, and the pre hospital time was longer than that of the survival group. The differences were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that after adjusting for confounding factors such as age, male proportion, body mass index, proportion of old myocardial infarction, proportion of hypertension, and proportion of PCI history, advanced age, long pre hospital time, failure to receive emergency PCI, elevated peripheral blood NLR, and elevated serum TMAO were independent risk factors for in-hospital mortality in AMICS patients ( P<0.05). The predictive model was obtained as 0.734×age+ 0.277×pre hospital time+ 2.263×failure to receive emergency PCI+ 0.549×peripheral blood NLR+ 0.608×serum TMAO-26.923. The ROC curve results showed that the area under the curve (AUC) values of peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and predictive model indicators for predicting in-hospital mortality events in AMICS patients were 0.744, 0.781, 0.825, and 0.921, respectively. When the optimal cutoff value was taken, the sensitivities were 0.880, 0.520, 0.680, and 0.880, and the specificities were 0.526, 0.923, 0.872, and 0.821, respectively. Conclusions:Advanced age, long pre hospital duration, failure to undergo emergency PCI, elevated peripheral blood NLR, and elevated serum TMAO are independent risk factors for in-hospital mortality in AMICS patients. Peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and prediction models all have certain predictive value for in-hospital mortality events in AMICS patients. Among them, the sensitivity and specificity of the prediction models are high, and the efficacy is good.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Objective:To determine the median effective dose (ED 50) of oliceridine combined with propofol for analgesia during induced abortion in patients with different labor histories. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-45 yr, with a body mass index of 20-28 kg/m 2, scheduled for elective induced abortion at Henan Provincial People′s Hospital (Zhengzhou University People′s Hospital) from July 1, 2024 to August 20, 2024, were selected. Patients were divided into a delivery group (group D) and a non-delivery group (group N) based on their histories of vaginal delivery. The modified Dixon′s up and down method was used to conduct the trial. Oliceridine was intravenously injected at a dose of 0.015 mg/kg in the first patient in each group, and the dose was determined based on the intraoperative body movement. The positive response was defined as the body movement of grade 2 or higher during induced abortion. If the response was positive, the next patient received a higher dose of oliceridine, or conversely, a lower dose was given. The ratio between the two successive concentrations was 1.2, and the trial was terminated until 7 turning points were achieved. The ED 50 and 95% confidence interval were calculated using the Dixon sequential method formula. The occurrence of adverse reactions was recorded. Results:A total of 54 patients were included in this study, with 25 in group D and 29 in group N. The ED 50 and 95% confidence interval of oliceridine for painless abortion were 0.019 (0.014-0.031) mg/kg and 0.026 (0.020-0.044) mg/kg in group D and group N, respectively. Compared with group D, the ED 50 of oliceridine for analgesia during induced abortion was significantly increased when combined with propofol in group N ( P<0.05). Patients in both groups experienced dizziness after intravenous oliceridine injection, and no other adverse reactions such as injection pain were observed. Conclusions:When combined with propofol, the ED 50 of oliceridine for analgesia is 0.019 mg/kg and 0.026 mg/kg during induced abortion in patients with and without vaginal delivery history, respectively. The analgesic potency of oliceridine is decreased in patients without a history of vaginal delivery compared to patients with a history of vaginal delivery.

Objective:To determine the median effective dose (ED 50) of oliceridine combined with propofol for analgesia during induced abortion in patients with different labor histories. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-45 yr, with a body mass index of 20-28 kg/m 2, scheduled for elective induced abortion at Henan Provincial People′s Hospital (Zhengzhou University People′s Hospital) from July 1, 2024 to August 20, 2024, were selected. Patients were divided into a delivery group (group D) and a non-delivery group (group N) based on their histories of vaginal delivery. The modified Dixon′s up and down method was used to conduct the trial. Oliceridine was intravenously injected at a dose of 0.015 mg/kg in the first patient in each group, and the dose was determined based on the intraoperative body movement. The positive response was defined as the body movement of grade 2 or higher during induced abortion. If the response was positive, the next patient received a higher dose of oliceridine, or conversely, a lower dose was given. The ratio between the two successive concentrations was 1.2, and the trial was terminated until 7 turning points were achieved. The ED 50 and 95% confidence interval were calculated using the Dixon sequential method formula. The occurrence of adverse reactions was recorded. Results:A total of 54 patients were included in this study, with 25 in group D and 29 in group N. The ED 50 and 95% confidence interval of oliceridine for painless abortion were 0.019 (0.014-0.031) mg/kg and 0.026 (0.020-0.044) mg/kg in group D and group N, respectively. Compared with group D, the ED 50 of oliceridine for analgesia during induced abortion was significantly increased when combined with propofol in group N ( P<0.05). Patients in both groups experienced dizziness after intravenous oliceridine injection, and no other adverse reactions such as injection pain were observed. Conclusions:When combined with propofol, the ED 50 of oliceridine for analgesia is 0.019 mg/kg and 0.026 mg/kg during induced abortion in patients with and without vaginal delivery history, respectively. The analgesic potency of oliceridine is decreased in patients without a history of vaginal delivery compared to patients with a history of vaginal delivery.