Background::Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods::In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF. Results::We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion::We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

This article introduced the background,drafting process,and main content of the Interim Measures for the Management of Surplus Drugs in Medical Institutions of Hubei Province(referred as the Measures).It focused on explaining the definition of surplus drugs and analyzing the requirements for drug dismantling,surplus drug billing,recovery and use procedures,special fund management,and duties and responsibilities of management departments.This paper aimed to guide readers to learn the Measures,understand the Measures and implement the Measures.It would help to improve the efficiency of medical resources,ensure medication safety,reduce patients'medication burden,and promote the rational use of medical insurance funds.

Objective To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis(AM)and Ishikawa cells to explore the pathogenesis of AM.Methods Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics(control group).The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting,and the levels of glucose and lactic acid were determined.An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay,cell migration and invasion abilities with Transwell migration and invasion assays,and glycolytic capacity by determining the extracellular acidification rate.Results Compared with those in the control group,the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125(CA125),increased mRNA expression levels of Notch1,HK2 and PDHA and protein expressions of Notch1,GLUT1,HK2,PKM and PDHA,lowered glucose level and increased lactate level.The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve.Conclusion The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation,migration,invasion and glycolysis of endometrial cells.

Objective To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis(AM)and Ishikawa cells to explore the pathogenesis of AM.Methods Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics(control group).The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting,and the levels of glucose and lactic acid were determined.An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay,cell migration and invasion abilities with Transwell migration and invasion assays,and glycolytic capacity by determining the extracellular acidification rate.Results Compared with those in the control group,the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125(CA125),increased mRNA expression levels of Notch1,HK2 and PDHA and protein expressions of Notch1,GLUT1,HK2,PKM and PDHA,lowered glucose level and increased lactate level.The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve.Conclusion The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation,migration,invasion and glycolysis of endometrial cells.

Objective:To investigate the serum level of fatty acid binding protein 1 (FABP1) and its relationship with Helicobacter pylori (Hp) infection in patients with gastric cancer. Methods:Forty gastric cancer patients (gastric cancer group) who were hospitalized in Affiliated Hospital of Qinghai University from August 2021 to August 2022 were selected as the research subjects, and 40 physical examination subjects during the same period were selected as the normal control group and 40 chronic atrophic gastritis patients were selected as the CAG group. The Hp infection were detected by 13C breath test, and the levels of serum FABP1 were detected by enzyme-linked immunosorbent assay. The Hp infection status, serum FABP1 levels, and the relationship between the two in the three groups of study subjects were analyzed. And the relationships between the level of serum FABP1 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value of serum FABP1, CA19-9, CA72-4 and combined test of 3 indexes were evaluated by receiver operating characteristic (ROC) curve. Results:The Hp infection rates in the control group, CAG group, and gastric cancer group were 32.50% (13/40), 55.00% (22/40), and 60.00% (24/40), respectively, with a statistically significant difference ( χ2=6.87, P=0.032). Among them, the Hp infection rate in the control group was compared with that in the gastric cancer group, with a statistically significant difference ( P<0.05), and there were no statistically significant differences between the CAG group and the control group, the gastric cancer group (both P>0.05). The levels of serum FABP1 in the control group, CAG group, and gastric cancer group were [63.47 (37.53, 71.59) ] ng/ml, [65.26 (51.15, 79.67) ] ng/ml, and [72.84 (53.44, 82.25) ] ng/ml, respectively, with a statistically significant difference ( H=6.62, P=0.037). Among them, there was a statistically significant difference between the control group and the gastric cancer group ( H=19.93, P=0.031), while there were no statistically significant differences between the CAG group and the control group, the gastric cancer group ( H=1.50, P=0.133; H=1.09, P=0.277). Among all study subjects, the levels of serum FABP1 in the Hp positive group ( n=59) and Hp negative group ( n=61) were [77.05 (68.90, 83.54) ] ng/ml and [47.80 (37.76, 63.32) ] ng/ml, respectively, with a statistically significant difference ( Z=7.45, P<0.001). In the control group, the levels of FABP1 in the serum of Hp positive and Hp negative persons were [77.34 (68.84, 86.31) ] ng/ml and [39.79 (36.83, 63.75) ] ng/ml, respectively, with a statistically significant difference ( Z=4.46, P<0.001). In the CAG group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [76.51 (65.30, 80.97) ] ng/ml and [49.34 (39.92, 59.41) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). In the gastric cancer group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [77.15 (72.62, 84.13) ] ng/ml and [50.57 (44.54, 68.97) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). There were significant correlations between the serum level of FABP1 and smoking ( t=2.54, P=0.015), tumor diameter ( t=2.23, P=0.035), and lymph node metastasis ( t=3.22, P=0.003) in gastric cancer patients. And there were no significant correlations between FABP1 and gender ( t=0.98, P=0.333), age ( t=1.60, P=0.117), alcohol consumption ( Z=0.10, P=0.925), tumor site ( F=1.06, P=0.356), degree of differentiation ( t=0.61, P=0.545), the depth of infiltration ( t=1.41, P=0.166), distant metastasis ( Z=1.96, P=0.050) and TNM staging ( Z=0.66, P=0.508). ROC curve analysis showed that the area under the curve (AUC) of serum FABP1 for gastric cancer diagnosis was 0.62, 95% CI: 0.51-0.72, the sensitivity and specificity were 57.50% and 68.70%, respectively; the AUC of CA19-9 for gastric cancer diagnosis was 0.89, 95% CI: 0.83-0.95, the sensitivity and specificity were 77.50%, 86.30%, respectively; the AUC of CA72-4 for gastric cancer diagnosis was 0.88, 95% CI: 0.81-0.94, the sensitivity and specificity were 70.00%, 93.70%, respectively; the AUC of combined test of 3 indexes for gastric cancer diagnosis was 0.91, 95% CI: 0.82-0.97, the sensitivity and specificity were 67.50% and 95.00%, respectively. Conclusion:The Hp infection rate of gastric cancer patients is higher than that of the health examiners, the serum FABP1 level of gastric cancer patients is higher than that of the healthy health examiners, the serum FABP1 level of Hp positive persons is higher than that of Hp negative persons, and Hp infection and FABP1 level may have a common carcinogenic mechanism in the occurrence and development of gastric cancer.

Objective:To explore any effect of mechanical vibration on the expression of estrogen and brain-derived neurotrophic factor (BDNF) in ovariectomized rats with an osteoporotic fracture.Methods:Thirty 3-month-old female Wistar rats were divided randomly into a control group, an ovariectomy group and a vibration group, each of 10. Fractures were induced in the rats of all three groups. Twenty minutes of whole-body vertical vibration was applied to the vibration group at a frequency of 35Hz, 5 days a week for 6 weeks. After 2 and 6 weeks the fracture healing of each group was evaluated using X-rays, the levels of hippocampal estrogen were measured using enzyme-linked immunosorbent assays and fracture-end BDNF was quantified by immunoblotting.Results:After 2 and 6 weeks of vibration the average fracture healing in the vibration group was significantly greater than in the other 2 groups. The average estrogen content in the hippocampus of the vibration group was significantly higher than in the other 2 groups after both 2 and 6 weeks, while the average BDNF content in their fracture ends was significantly lower. The BDNF expression at the fracture end was significantly correlated with the fracture healing.Conclusion:Mechanical vibration can promote the expression of estrogen and BDNF in the hippocampus and accelerate fracture healing in osteoporotic rats.

Sarcopenia etiology is diverse and the pathogenesis is complex.It is closely related to limited activity, malnutrition and a variety of clinical diseases, which seriously affects the quality of life in the elderly and has become a global common health problem.This review focuses on the literature of non-drug interventions for sarcopenia in the past five years, focusing on the relationship of multimodal exercise, intestinal flora, parenteral nutrition and comprehensive intervention with sarcopenia, in order to provide a new basis for formulating scientific and effective non-drug intervention for sarcopenia.

AIM: To observe the anesthetic effect of nalbuphine used in ultrasound-guided transvaginal oocyte retrieval and its effect on embryo quality and pregnancy outcome. METHODS: Four-hundred patients who underwent ultrasound-guided transvaginal oocyte retrieval were randomly divided into two groups (n=200): nalbuphine group (N group) and control group (C group). The patients were in the bladder lithotomy position. Patients in N group were given nalbuphine 0.1 mg/kg intravenously 2 minutes before induction of anesthesia, patients in C group were given normal saline intravenously, and patients in both groups were induced with propofol 1.5 mg/kg. The patients were kept breathing spontaneously, and they were given intravenous injections of propofol (2 mg•kg

Objective:To investigate the clinical efficacy and safety of domestic bortezomib in the treatment of patients with multiple myeloma (MM).Methods:The data of 60 MM patients treated with domestic bortezomib as the basic chemotherapy regimen in 5 medical centers of Qilu Hospital of Shandong University, Heze Municipal Hospital, Weifang People's Hospital, Binzhou Medical University Hospital, Zibo Central Hospital in Shandong Province from January 2018 to June 2019 were retrospectively analyzed, 52 of which were newly treated patients and 8 were relapsed and refractory patients. The patients received at least 2 courses of combined chemotherapy based on domestic bortezomib, and the efficacy was assessed and evaluated every 2 courses.Results:Follow-up until June 30, 2019 showed that some patients were unable to return to the hospital for regular treatment. All patients completed at least 2 courses of treatment, with an overall effective rate (ORR) of 76.7% (46/60); 42 patients completed 4 courses of treatment, with an ORR of 78.6% (33/42); 30 patients completed 6 courses of treatment, with an ORR of 86.7% (26/30); there was no significant difference in ORR of 2, 4 and 6 courses ( P > 0.05). The complete remission+very good partial remission rates of 2, 4 and 6 courses were 16.7% (10/60), 47.6% (20/42) and 66.7% (20/30), respectively, and the difference was statistically significant ( P < 0.01). During the treatment, the adverse events mainly included infection, peripheral neuropathy, herpes, digestive tract symptoms, hematologic toxicities and so on, which were light and moderate mostly, and most of them can be reversed. The total incidence of adverse events in patients who completed 2, 4 and 6 courses of treatment were 91.7% (55/60), 66.7% (28/42) and 36.7% (11/30), respectively. Conclusions:The domestic bortezomib-based chemotherapy regimens have good efficacy in the treatment of MM. The incidence of adverse events is similar to that of the original drug, and patients can tolerate the adverse events.