Nowadays,the prevalence of nonalcoholic fatty liver disease(NAFLD)is constantly rising in China and globally,and its incidence rate is increasing year by year,which has seriously affected human life and health.Lipophagy is molecular chaperone-mediated autophagy and has the functions of promoting lipolysis,maintaining the lipid homeostasis of hepatocytes,and alleviating hepatocyte fatty degeneration.Lipophagy has three main processes of lipid droplet catabolism,lipid droplet autophagy,and fatty acid β-oxidation,which are regulated by key genes,receptors,and enzymes.Currently,important advances have been achieved for the intervention methods of traditional Chinese medicine,Western medicine,diet,and exercise in the research on lipophagy,which provides new perspectives for the prevention and treatment strategies for NAFLD.

Liver transplant patients require lifelong immunotherapy， and if they are infected by SARS-Cov-2， their immune function will face double whammy. This report described the integrated approach of traditional Chinese and western medicine in the treatment of a liver transplant patient with severe COVID-19. The treatment was involved with western medicine such as antiviral， immunosuppressive， focusing on maintaining immune balance. Traditional Chinese medicine was given based on the differentiation of syndromes， targeting at the core pathogenesis and using methods such as promoting qi circulation， clearing heat and resolving dampness， draining lung and relieving panting. Following the treatment， the patient exhibited notable improvement in clinical symptoms and liver function， leading to the effective cessation of disease progression and a shortened recovery period.

Objective To observe the effects of the intercellular gap junction (GJIC) composed of connexin 43(Cx43) in mesenchymal stem cells (MSCs) from different sources and their signals on the biological behavior of multiple myeloma (MM) lateral population cells (SP cells), and to explore its possible mechanism. Methods Mesenchymal stem cells (MSCs) from different sources were isolated and cultured. SP cells of MM cell line RPMI 8266 were sorted by flow cytometry. RT-PCR and Western blot were used to detect the expression of Cx43 gene and protein in MSCs, RPMI 8266 and SP cells from different sources. The effects of MSCs from different sources on SP cell cycle, Cx43 protein expression, colony formation ability in vitro, stem cell related gene expression, cytokine secretion and drug resistance were observed. Results There was no significant difference in morphology and phenotype between MM-MSCs and ND-MSCs. Both MM-MSCs and RPMI 8266 cells expressed a higher level of Cx43. Co-culture with MM-MSCs induced more SP cells to enter G0 phase (P<0.001). The expressions of c-myc, Kif4 and Sox2 genes in SP cells were significantly up-regulated, while the expression of Oct-4 gene was down-regulated. After adding α-GA, c-myc, Kif4 and Sox2 were down-regulated in varying degrees, but there was no significant difference. The expression of Cx43 was up-regulated by (31.00±2)% and (39.00±2)%, respectively. The colony formation ability in vitro was up-regulated, and the addition of α-GA could partially inhibit this effect. A small amount of c-myc, Kif4, Sox2 and Oct-4 genes were expressed in RPMI 8266. These genes were significantly up-regulated in SP cell subpopulation. MM-MSCs secreted high levels of interleukin (IL)-6. After co-culture with SP cells, the expressions of IL-6, IL-10 and TGF-β in the supernatant of MM-MSCs were up-regulated (P=0.0072, P=0.037). bFGF and IL-17 had no significant change. After adding α-GA, the levels of IL-6, IL-10 and TGF-β in the supernatant decreased. MM cells were sensitive to bortezomib (BTZ) induced apoptosis, but SP cells were less sensitive. Co-culture with MM-MSCs significantly reduced BTZ-mediated apoptosis. The addition of α-GA partially restored the sensitivity of MM cells to bortezomib. Conclusion MM-MSCs and multiple myeloma SP cells up-regulate the expression of Cx43 protein, form more GJIC, and promote the proliferation and drug resistance of SP cells by changing the cytokine secretion profile of MSCs, which may be one of the reasons for the recurrence of MM.

Objective To investigate the role of monocyte subsets in the pathogenesis of type 2 diabetes mellitus(T2DM), the expression was detected on lipoprotein-associated phospholipase A2(LP-PLA2) mRNA in peripheral blood monocytes subsets of type 2 diabetic patients. Methods After the peripheral blood of 32 type 2 diabetic patients and 22 healthy controls were collected,the percentages of the monocytes subsets were detected by flow cytometry. The expression of LP-PLA2 mRNA in monocytes subsets were detected by PCR. After monocyte subsets of healthy subjects were induced into macrophages and stimulated by the serum of type 2 diabetic patients for 24h,LP-PLA2 mRNA expression was detected. Results Compared with the control group, the percentage of classical monocytes in T2DM group was decreased, while the LP-PLA2 mRNA expression and percentage of nonclassical,intermediate monocytes were significantly increased(all P<0.05). In addition,the homeostasis model assessment for insulin resistance index was positively correlated with LP-PLA2 mRNA expression in non-classical(P<0.05)and intermediate monocytes(P<0.01)of type 2 diabetic patients. Compared with type 2 diabetic patients without carotid atherosclerosis, the levels of LP-PLA2 mRNA in intermediate and nonclassical monocytes were significantly higher than those in type 2 diabetic patients with carotid atherosclerosis(P<0.05). The level of LP-PLA2 mRNA in non-classical monocytes-derived macrophages stimulated with the serum of type 2 diabetic patients was significantly higher than that in the control group(P<0.05). Conclusion Monocytes subsets from type 2 diabetic patients are abnormally skewed toward to intermediate and non-classical monocytes with high expression of LP-PLA2 mRNA,which may play an important role in the pathogenesis of type 2 diabetes mellitus and atherosclerosis.

Objective To investigate serum alpha2-Heremans-Schmid glycoprotein ( AHSG ) level and its relationship with associated clinical parameters in subjects with simple overweight and obesity. Methods Forty-nine subjects with obesity ( OB group) , 176 subjects with overweight ( OW group) , and 327 individuals with normal weight ( NW group) were randomly enrolled. The clinical data were collected and serum levels of AHSG and adiponectin ( APN) were determined by ELISA. The associations of serum AHSG level with other clinical parameters were assessed by Pearson correlation analysis and multiple linear regressive model. Results Serum AHSG levels were higher in OW and OB groups than that in NW group[(276. 30 and 302. 10 vs 241. 60)μg/ml], being especially higher in OB group (P<0. 05 or P<0. 01). Serum AHSG level in NW group was positively associated with fasting plasma glucose, homoeostasis model assessment of insulin resistance index, C-reactive protein (CRP), triglycerides, and free fatty acids ( FFA ) , but negatively associated with age and APN. In OW and OB groups, AHSG was also positively associated with body mass index, waist hip ratio(WHR), and low density lipoprotein cholesterol(P<0. 05 or P<0. 01) except the aforementioned clinical parameters. In multiple linear regression model, AHSG was positively associated with WHR, CRP, and FFA, and was negatively associated with APN ( P<0. 05 or P<0. 01). Conclusion The raised AHSG level in overweight and obese subjects may be a risk factor for obesity-related diseases.

OBJECTIVE:To compare clinical efficacy of Xiaoshi lidan capsules and Ursodeoxycholic acid capsules in the treat-ment of chronic cholesterol gallstone cholecystitis. METHODS:120 patients with chronic cholesterol gallstone cholecystitis in our hospital were selected and divided into observation group and control group according to random number table,with 60 cases in each group. Observation group was given Xiaoshi lidan capsules 1.2 g,po,tid(after the meal);control group was given Ursodeoxycholic acid capsules 250 mg,po,qd(after dinner). Both group received treatment for 6 months. Effective rate of litholysis were observed in 2 groups as well as abdominal pain score [PRI,VAS score,present pain intensity(PPI)],the thickness of gallbladder wall before and after treatment. Clinical efficacy and the occurrence of ADR were compared between 2 groups during treatment. RESULTS:3 pa-tients withdrew from the observation group and 1 patient withdrew from the control group. Before treatment,there was no statistical significance in PRI,VAS score,PPI and the thickness of gallbladder wall between 2 groups(P>0.05). After treatment,above index-es of 2 groups were decreased significantly,while PRI,VAS score and PPI in observation group was significantly lower than in con-trol group,with statistical significance (P<0.05). The effective rate of litholysis (64.91%) in observation group was significantly lower than in control group (79.67%),with statistical significance (P<0.05). Total effective rate of observation group (57.89%) was slightly higher than that of control group(54.24%),without statistical significance(P>0.05). There was no statistical signifi-cance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Xiaoshi lidan capsules are similar to Ursodeoxycholic acid capsules in clinical efficacy for chronic cholesterol gallstone cholecystitis with good safety,and can be used as optional drug ex-cept for chronic cholesterol gallstone cholecystitis.

The association between serum fetuin A and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus(T2DM) was investigated.Serum levels of fetuin-A and adiponectin were measured by ELISA and the clinical data were collected in 101 T2DM patients with normal albuminuria (NA group),87 patients with microalbuminuria (MA group),44 patients with overt albuminuria (OA group),and 130 normal control subjects (NC group).Fetuin-A levels increased progressively from NC,NA,MA,to OA groups,and there were significant differences among groups(P＜0.05 or P＜0.01).Fetuin-A level in patients was positively associated with duration of illness,urinary albumin to creatinine ratio (ACR),fasting blood glucose,2-hour postprandial blood glucose,and C-reactive protein(CRP,P＜0.05 or P＜0.01),but was negatively associated with age and adiponectin (all P＜ 0.01).Multiple stepwise regression analysis indicated that duration of diabetes,fetuin-A,CRP,and adiponectin were independent determinants for ACR (all P ＜ 0.01).Fetuin-A may be involved in the development and pathogenesis of DN by proinflammatory effects and repressing adiponectin production.

Objective To observe the impact of mild hypothermia (MH)on the reactive oxygen species (ROS)and expression of cacpase-3mRNA and light chain 3 (LC3,a subunit of immunoglobulin)in hippocampus nerve cells of rats after cardiopulmonary resuscitation (CPR).Methods A total of 65 healthy male Sprague Dawley (SD)adult rats were randomly (random number)divided into 2 groups:blank control group (n =5)and CPR group (n =60).Cardiac arrest (CA)was induced in rats of CPR group by asphyxia.The survival rats after CPR were randomly (random number)divided into 2 groups:normothermia CPR group (NT)and hypothermia CPR group (HT).Homeothermia of 37 ℃ was maintained in NT group after restoration of spontaneous circulation (ROSC),and hypothermal intervention to 32 ℃ was carried out in HT group for 4 hours immediately after ROSC.Both NT group and HT group were then randomly divided to 2 subgroups 12 hours and 24 hours after ROSC (NT-12,NT-24,HT-12,HT-24 subgroups).During observation,the neurological deficit (NDS)of rats was scored,then the bilateral hippocampi were obtained from rats'head,and monoplast suspension of fresh hippocampus tissue was made immediately to determine the level of intracellular ROS by flow cytometry.Transmission electron microscope was used to observe the ultrastructure changes of cellular nucleus and mitochondria.Reverse transcription-polymerase chain reaction (RT-PCR)was used to determine the expression of caspase-3mRNA and Western-blotting (WB)was used to determine the level of LC3 in frozen hippocampus tissue.Measured data were analyzed with paired sample T test and One-Way ANOVA.Results Of 60 rats with CA,44 were successfully resuscitated (73%)and 33 survived until the end of the experiment (55%).The NDSs of rats in NT and HT groups were significantly reduced in comparison with BC group (F=8.107,P<0.05),while the NDSs of rats in HT-12 subgroup and HT-24 subgroup were significantly increased in comparison with NDSs of rats in NT-12 subgroup and NT-24 subgroup,respectively (t=9.692,P<0.01;t=14.374,P<0.01 ).The ROS in hippocampus nerve cells of rats in NT group and HT group were significantly increased compared to BC group (F=16.824,P<0.05 ),whereas the ROS in HT-12 and HT-24 subgroups were significantly reduced compared to ROS in NT-12 and NT-24 subgroups,respectively (t =9.836,P<0.01;t =7.499,P<0.01).The expressions of caspase-3 mRNA in hippocampus nerve cells of rats in NT and HT groups were significantly increased compared to BC group (F=24.527,P<0.05),while the expressions of caspase-3 mRNA in rats of HT-12 and HT-24 subgroups were significantly reduced compared to NT-12 and NT-24 subgroups,respectively (t =6.935,P <0.01;t =4.317,P <0.01 ).The level of LC3B-II/I in hippocampus nerve cells of rats in NT and HT groups were significantly increased compared to BC group (F=6.584,P<0.05),while the levels of LC3B-II/I in rats of HT-12 and HT-24 subgroups were significantly reduced compared to NT-12 and NT-24 subgroups,respectively (t=10.836,P<0.001;t=2.653,P=0.02).Ultrastructure damage of nucleus and mitochondria in NT group was more evident compared to BC group,and eumorphism of nucleus and mitochondria were maintained in rats of HT group compared to NT group.Conclusions The mild hypothermia reduced the injury of nerve cells and improved the neurological function of rats survived from cardiac arrest likely by reducing ROS production of nerve cells and inhibition the expression of caspase-3mRNA and lowering the level of LC3 leading to reducing cellular apoptosis and massive autophagy in rats survived from cardiac arrest after CPR.

OBJECTIVE To determine the distribution and antibiotic resistance of bacteria isolated from cerebral spinal fluid in neurosurgical patients. METHODS Bacterial isolates from cerebral spinal fluid specimens in Department of Neurosurgery,Beijing Tiantan Hospital were collected from Jan 2000 to Dec 2004.Distribution and antibiotic resistance of pathogens were analyzed retrospectively. RESULTS Of 438 isolates,Gram positive cocci and Gram negative bacilli accounted for 72.1%(316 isolates) and 27.9%(122 isolates),respectively.The most frequently isolated pathogen was coagulasenegative staphylococci(53.7%) followed by Staphylococcus aureus(10.5%),Enterobacter spp(6.2%),Acinetobacter spp(6.2%),and Pseudomonas aeruginosa(3.7%).The most active compounds against Gram-negative bacilli were imipenem(87% susceptibility),piperacillin/tazobactam(77%),amikacin(68%),cefepime(64%) and ceftazidime(63% susceptibility).Imipenem,cefepime,ceftazidime,and piperacillin/tazobactam demonstrated excellent activity against most of Gram negative bacilli.In S.aureus and coagulase-negative staphylococci,oxacillin resistance strains accounted for 76% and 100%,respectively. CONCLUSIONS Prevailing pathogens are Gram positive cocci in intracranial infection after neurosurgical operation,especially coagulase-negative staphylococci and S.aureus.Data collected in present study will provide valuable information for prophylactic and empirical antibiotic use in post-operative intracranial infection.

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.

CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.