Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Osteocytes are the most abundant and long-lived cells in bone,serving as primary regulators of bone remodeling.Besides playing critical roles in endocrine regulation and calcium-phosphate metabolism,osteocytes are primary responders to mechanical stimuli,perceiving and responding to these stimuli directly and indirectly.The process of mechanotransduction in osteocytes is a complex and finely tuned regulation involving interactions between the cell and its surrounding environment,neighboring cells,and various mechanosensors within the cells with distinct functions.The known major mechanosensors in osteocytes include primary cilia,Piezo ion channels,integrins,extracellular matrix,and connexin-based intercellular junctions.These mechanosensors play crucial roles in osteocytes,perceiving and transducing mechanical signals to regulate bone homeostasis.This review aims to provide a systematic introduction to these five mechanosensors,offering new perspectives and insights into understanding how osteocytes respond to mechanical stimuli and maintain bone tissue homeostasis.

Objective:To explore the impact of weekend hospitalization on total hospitalization expenses for elderly patients with hip fracture under the geriatric orthopedic co-management.Methods:A retrospective analysis was conducted to analyze the clinical data of elderly patients with hip fracture who had been hospitalized for surgical treatment at Beijing Jishuitan Hospital from May 2015 to December 2020. They were divided into 2 groups based on their admission date. Group A was admitted from Monday to Thursday while Group B from Friday to Sunday. The general demographic data, diagnostic information, comorbidities, hospitalization expenses of the patients were collected. The differences in total hospitalization expenses, hospitalization time, rate of surgery within 48 hours and rate of hospital mortality between the 2 groups were analyzed by rank sum test, chi square test, correlation analysis, and multiple linear regression.Results:A total of 6,075 patients with hip fracture were included in this study, including 1,675 males and 4,400 females with a median age of 80 (74, 85) years. There were 3,935 ones in group A and 2,140 ones in group B. The total hospitalization expenses for group A was 58,160.52 (49,215.45, 72,748.94) yuan, insignificantly lower than those for Group B [58,412.90 (49,163.58, 72,712.61) yuan] ( P>0.05). The rate of surgery within 48 hours for group A was 75.8% (2,984/3,935), significantly higher than that for group B [49.3% (1,054/2,140)]. The hospitalization time for group A was 5 (4, 7) days, significantly less than that for group B [5 (4, 7) days] ( P<0.05). There was no significant difference in the rate of hospital mortality between the 2 groups ( P>0.05). Multiple linear regression analysis showed that total hospitalization expenses were significantly higher for patients admitted on weekends, hospitalization time was positively correlated with total hospitalization expenses, and total hospitalization expenses were significantly lower for the patients undergoing surgery within 48 hours ( P<0.05). Conclusion:Admission on weekends can increase total hospitalization expenses, prolong hospitalization time, and reduce rate of surgery within 48 hours for elderly patients with hip fracture.

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

This article analyzes the clinical manifestations and magnetic resonance imaging (MRI) data of 2 patients with hypoxic encephalopathy after simple asphyxia gas poisoning. Both patients were in a moderate coma after being poisoned, and the arterial blood lactic acid level and carbon dioxide partial pressure were higher than the normal range within 1 week after poisoning. Two patients were cured and discharged after being treated with oxygen therapy and glucocorticoids. The prognosis was good.

Objective:Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells.Methods:HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test.Results:AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 ( P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion:AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.

OBJECTIVE: To explore the characteristics of peripheral nerve injury caused by occupational acute trimethyltin chloride(TMT) poisoning. METHODS: The clinical manifestations and test data of neurotic electrophysiology, pure tone hearing threshold and acoustic immittance in 16 patients with occupational acute TMT poisoning were retrospectively analyzed. The patients were followed up after 6 months of discharge. RESULTS: Among the 16 cases of occupational acute TMT poisoning, 6, 4 and 6 cases were with mild, moderate and severe poisoning, respectively. For the firstly appeared symptoms, 7 cases had abnormal mental behavior and memory loss, 5 cases had tinnitus and hearing loss, 5 cases had decreased visual acuity, 2 cases had diplopia and 2 cases had binocular pain. The main clinical manifestations included 8 cases of disturbance of consciousness, and 6 cases of abnormal orientation and aggressive behavior. After correction of hypokalemia, 7 cases of patients had limb muscle weakness, hypomyotonia and weakened tendinous reflect, 9 cases had decreased tactile sensation below the groin in the lower limbs, and 6 cases had instability of walking. The main manifestations of neuroelectrophysiological detection were: 9 patients(accounting for 56.3%) showed abnormal neuroelectromyography, 4 cases of severe poisoning had damaged motor nerve, sensory nerve axon and myelin sheath, and the proximal nerve was also partially damaged. There were 2 cases of moderate poisoning showing abnormal symptoms, the axon and myelin sheath of sensory nerve were damaged, one common peroneal nerve was demyelinated. Three cases of mild poisoning had one common peroneal nerve axon damaged, one proximal tibial nerve damaged, and the axon and myelin sheath of sensory nerve were damaged. Brainstem auditory evoked potential I wave and visual evoked potential P100 latency prolonged and amplitude decreased in some of the patients with mild, moderate and severe poisoning. The sensorineural hearing loss occurred in 81.3% of patients. CONCLUSION: Occupational acute TMT poisoning can cause damage to motor nerve, sensory nerve axon and myelin sheath of extremities. Both distal and proximal nerves might be involved. It can also damage cochlear hair cells and optic nerve. Attention should be paid to the early treatment of peripheral nerve damage, cochlear hair cell and optic nerve damage caused by TMT.

This article analyzes the clinical manifestations and magnetic resonance imaging (MRI) data of 2 patients with hypoxic encephalopathy after simple asphyxia gas poisoning. Both patients were in a moderate coma after being poisoned, and the arterial blood lactic acid level and carbon dioxide partial pressure were higher than the normal range within 1 week after poisoning. Two patients were cured and discharged after being treated with oxygen therapy and glucocorticoids. The prognosis was good.

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm³), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ² = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.