Autophagy is a catabolism process in which lysosomes degrade damaged organelles, protein aggregates and recover nutrients. Studies have shown that autophagy could protect the structure and function of islet β cell and maintaining normal secretion of insulin. In addition, autophagy plays important roles in the occurrence and development of diabetes mellitus by reducing oxidative stress, preventing apoptosis and removing ubiquitination protein aggregates. Therefore, autophagy may be a new target for the prevention and treatment of diabetes. At present, hypoglycemic drugs have been proved to play positive roles by regulating autophagy including thiazolidine dione and guanidine. Therefore, this paper will review autophagy definition, the role of autophagy in diabetes mellitus and autophagy-related hypoglycemic drugs, providing a new direction for clinical treatment of diabetes.

Objective:To investigate gender measurement invariance of the Perceived Social Support Scale(PSSS)in people aged 50 years and older.Methods:A total of 1013 adults(50-96 years old)in Beijing, Hunan and Shandong were tested by using PSSS.The measurement invariance of PSSS between middle-aged and elderly males and females was analyzed.Differences in PSSS total scores and subscale scores between males and females were examined.Results:The equivalence test results of each item in the questionnaire met the requirements of the metrology(△CFI≥0.010, △TLI≥0.010, △RSMEA≤0.015), indicating that the hypotheses of morphological equivalence, weak equivalence, strong equivalence and strict equivalence of PSSS were all valid in the middle-aged and elderly population regardless of gender.In addition, middle-aged and elderly females had higher scores in family support, support from friends, support from other people and perceived social support than their male counterparts( P<0.05). Conclusions:PSSS has cross-gender equivalence in middle-aged and elderly people.Thus, differences in PSSS can reflect the perceived social support level in middle-aged and elderly people of different genders.

Objective:To observe the effects of acupuncture and moxibustion on ubiquitin-like containing PHD and RING finger domains 1(UHRF1)and DNA methyltransferase 1(DNMT1)in ectopic endometrium of rats with endometriosis(EMS). Methods:Forty Sprague-Dawley rats were randomly divided into a sham operation group with 10 rats and a model-building group with 30 rats according to body mass.EMS rat models were established in the model-building group and then were divided into a model group,an acupuncture and moxibustion group,and a progesterone group,with 10 rats in each group.All rats were fixed by a fixator.The sham operation group and the model group were given normal saline by gavage.The acupuncture and moxibustion group received acupuncture at Xuehai(SP10)and Sanyinjiao(SP6),moxibustion at Guanyuan(CV4),and gavage of normal saline.The progesterone group was given the mixed liquid made of dydrogesterone and normal saline by gavage.After 28 d of treatments,the three diameters(length,width,and height)of EMS rats'ectopic cysts were measured,the cyst volumes were calculated,the volumes before intervention were subtracted,and the difference values were used to evaluate the growth of ectopic cysts.UHRF1 and DNMT1 mRNA and protein levels in normal endometrium,eutopic endometrium,and ectopic endometrium were detected by real-time polymerase chain reaction and immunohistochemistry. Results:There was no significant difference in the ectopic cyst volume difference between the acupuncture and moxibustion group and the progesterone group(P>0.05),but they were smaller than that of the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the ectopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of DNMT1 mRNA and UHRF1 protein in the eutopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of UHRF1 mRNA and protein and the level of DNMT1 protein in the ectopic endometrium of the acupuncture and moxibustion group were higher than those in the model group(P<0.05),and the level of UHRF1 mRNA was higher than that in the progesterone group(P<0.05).The level of DNMT1 mRNA in the eutopic endometrium of the acupuncture and moxibustion group was higher than that in the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the acupuncture and moxibustion group were insignificantly different from those in the normal endometrium(P>0.05). Conclusion:Acupuncture and moxibustion may up-regulate the levels of UHRF1 mRNA and UHRF1 and DNMT1 proteins in the ectopic endometrium to the normal level so as to reduce the volume of ectopic cysts and cure EMS in rats.

Acute pancreatitis (AP) is a common acute abdominal disease in clinical practice. As the hepatic manifestation of metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) is closely associated with the severity and prognosis of AP. This article elaborates on the mechanism of action of NAFLD in the development and progression of AP and further points out that NAFLD can induce AP and aggravate its severity through many ways.

Objective A comparison of different routes for the administration of clodronate disodium liposomes to determine the most effective method of rat endometrial macrophage clearance.Methods Female 8-week-old SD rats were randomly divided into a unilateral control group(injected with 100 μL PBS liposomes into the left uterine cavity),unilateral clearance group(injected with 100 μL clodronate liposomes into the right uterine cavity),bilateral control group(injected with 100 μL PBS liposomes into the bilateral intrauterine),bilateral clearance group(injected with 100 μL clodronate liposomes into the bilateral intrauterine),whole-body control group(injected with 500 μL PBS liposomes into the caudal vein),and whole-body clearance group(injected with 500 μL clodronate liposomes into the caudal vein).Hematoxylin and eosin staining was used to observe the morphology and structures of uterine and ovarian tissues,immunohistochemistry was used to observe the presence of macrophages in uterine and ovarian tissues,and flow cytometry was used to detect changes to macrophage cell counts in uterine and ovarian tissues.Results There were no significant differences in the structures or morphology of the uterus and ovary among the groups.Immunohistochemical staining showed that,compared to the control group,the unilateral and bilateral uterine clearance groups'population of terine macrophages was significantly decreased(P＜0.001),but there was no difference in the accumulation of macrophages in the ovary(P＞0.05).The number of macrophages in both uterine and ovarian tissues decreased in the whole-body clearance group(P＜0.01,P＜0.01).Compared with the unilateral and bilateral clearance groups,the whole-body clearance group had more macrophages in the ovarian tissues(P＜0.05).Flow cytometry showed that,compared with the control group,each clearance group's percentages of macrophages in the uterine tissue were significantly reduced(P＜0.001,P＜0.001,P＜0.05).Compared to the whole-body clearance group,the unilateral and bilateral clearance groups'endometrial macrophages had superior clearance activity(P＜0.05,P＜0.05).In addition,the number of macrophages in ovarian tissue decreased in all clearance groups compared to the control group.The decrease in macrophage number was most pronounced in the whole-body clearance group(P＜0.05),and there was no significant difference in numbers between the unilateral and bilateral clearance groups and the control group(P＞0.05).Conclusions Local injection of clodronate liposomes was more effective than caudal injection for clearing uterine macrophages,and the impact on ovarian macrophages was largely avoided.Thus local clodronate liposome injection is an improved method for establishing a local uterine macrophage clearance model.

Objective:To investigate the effect of hematopoietic stem cell transplantationon(HSCT)survival outcomes in older patients with myeloid neoplasms.Methods:We retrospectively analyzed the treatment outcomes of 54 patients aged≥55 years with myeloid neoplasms who underwent HSCT between January 2018 and May 2023 at Zhujiang Hospital of Southern Medical University.Results:Among the 54 pa-tients,45 had acute myeloid leukemia(AML)and 9 had myelodysplastic syndrome.The median age of the patients was 57.5(55-68)years.Fifty-three patients underwent hematopoietic reconstitution,with a median time to neutrophil reconstitution of 13(8-24)days and median time to platelet reconstitution of 15(9-75)days.The cumulative incidence was 23.3%for acute graft-versus-host disease(GVHD)and 24.6%for 3-year chronic GVHD.With a median follow-up of 28.2 months,the 3-year cumulative relapse rate(CIR)was 18%and 3-year non-relapse mortality rate was 28.3%.The 3-year relapse-free survival(RFS)rate was 58.2%and 3-year overall survival(OS)rate was 56.5%.Conclu-sions:HSCT is an effective and safe therapy for achieving long-term survival in older patients with myeloid tumors.

ObjectiveTo explore the mechanism of cucurbitacin B （CuB） in inhibiting cell proliferation and glycolysis. MethodCell counting kit-8 （CCK-8） was applied to investigate the effect of different concentrations of CuB （0， 40， 80， 120， 160， 200， 400， and 800 nmol·L^-1） on the proliferation of HuCCT1 cells. The effect of different concentrations of CuB （50， 100， and 200 nmol·L^-1） on the colony formation ability of HuCCT1 cells was detected by plate cloning assay. The effect of different concentrations of CuB （50， 100， 200 nmol·L^-1） on the HuCCT1 cell cycle was analyzed by flow cytometry. Visible spectrophotometry was employed to detect the activity of key glycolytic enzymes hexokinase （HK） and pyruvate kinase （PK）） and changes in glucose consumption， lactate production， and adenosine triphosphate （ATP） production in HuCCT1 cells after administration of different concentrations of CuB （50， 100， 200 nmol·L^-1）. Western blotting was used to assay the effect of CuB on the expression of cell cycle-related proteins， proliferation-related proteins， key glycolytic proteins， and Akt/mammalian target of rapamycin （mTOR） pathway-related proteins. ResultAs compared with the blank group， CuB at dose of 160-800 nmol·L^-1 after 24 h administration and CuB at dose of 80-800 nmol·L^-1 after 48 h administration inhibited the proliferation of HuCCT1 cells in a time- and dose-dependent manner （P<0.05， P<0.01）， and the median inhibitory concentration was 200 nmol·L^-1 48 h after administration. CuB can restrain the colony formation ability of HuCCT1 cells in a dose-dependent manner （P<0.01）， and block HuCCT1 cell cycle in G₂ phase （P<0.05， P<0.01）. CuB （100 and 200 nmol·L^-1） can suppress the activities of HK and PK and reduce cell glucose consumption and production of lactate and ATP （P<0.05， P<0.01）. Western blot results showed that CuB （100 and 200 nmol·L^-1） can inhibit the protein levels of cycle-related protein Cyclin B₁， proliferating cell nuclear antigen （PCNA）， HK1， HK2， PKM1， PKM2， phosphorylated Akt （p-Akt）， phosphorylated mTOR （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） （P<0.05， P<0.01）. ConclusionCuB can inhibit aerobic glycolysis in HuCCT1 cells via the Akt/mTOR pathway， thereby affecting cell proliferation.

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections. Six males and six females received single dose of either 25 mg or 50 mg levosulpiride, or multiple doses of 25 mg every 12 h for 5 consecutive days. In the single 25 mg study, the mean peak plasma concentration (C max) was 441 ng/mL, the mean area under the concentration-time curve from 0 to 36 h (AUC0-36) was 1724 ng h/mL, and the mean elimination half-life (t 1/2) was 7.0 h. In the single 50 mg study, the mean C max was 823 ng/mL, the mean AUC0-36 was 3748 ng·h/mL, and the mean t 1/2 was 6.8 h. After multiple doses of 25 mg levosulpiride, the average plasma concentration (C av) was 136 ng/mL, the fluctuation index (DF) was 3.60, and the accumulation ratio (R) was 1.2. Levosulpiride injections appeared to be well tolerated by the subjects, and can be used for successive administration.

ObjectiveTo investigate the effect and mechanism of osthole on the proliferation and apoptosis in human intrahepatic cholangiocarcinoma HuCCT1 cells. MethodThe effect of 10， 20， 40， 80， and 120 μmol·L^-1 osthole on the proliferation of HuCCT1 cells was detected by the cell counting kit-8 （CCK-8）. A blank group， and low-， medium-， and high-dose osthole groups （16， 32， and 64 μmol·L^-1） were set up. The effect of osthole on cell clone formation rate was detected by colony formation assay. The effect of osthole on cell cycle and apoptosis was detected by flow cytometry. The effect of osthole on cell apoptotic morphology was detected by Hoechst 33342 fluorescent staining. The effect of osthole on cell cycle protein cyclin B₁， proliferating cell nuclear antigen （PCNA）， cysteine-aspartic acid protease （Caspase）-9， Caspase-3， cleaved Caspase-9， cleaved Caspase-3， cleaved poly（ADP-ribose） polymerase （cleaved PARP）， B-cell lymphoma-2 （Bcl-2）， phosphorylated protein kinase B （p-Akt）， phosphorylated mammalian target of rapamycin （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） was detected by Western blot. ResultThe cell viability in the osthole group（40，80，120 μmol·L^-1） decreased （P<0.05，P<0.01）， with the half maximal inhibitory concentration （IC₅₀） of 63.8 μmol·L^-1 as compared with that in the blank group. Compared with the blank group， the osthole groups（32，64 μmol·L^-1）showed reduced clone formation rate （P<0.01）， increased number of cells in the G₂ phase （P<0.05，P<0.01）， decreased number of cells， increased pyknosis and fragmentation， increased apoptosis rate （P<0.05，P<0.01）， down-regulated expression of cyclin B₁， PCNA， Bcl-2， Caspase-3， Caspase-9， p-Akt， p-mTOR， and p-RPS6 （P<0.05，P<0.01）， and up-regulated expression of cleaved Caspase-3， cleaved Caspase-9， and cleaved PARP （P<0.05，P<0.01）. ConclusionOsthole can inhibit the proliferation and promote the apoptosis of HuCCT1 cells， and its mechanism may be related to the Akt/mTOR signaling pathway.

Background: Recent studies showed that the clinical outcome of moderately severe acute pancreatitis (MSAP) are different among different subgroups. Aims: To further subdivide MSAP, and explore the heterogeneity of MSAP subgroups. Methods: A retrospective analysis was performed on patients with acute pancreatitis (AP) from January 2016 to December 2020 at Northern Jiangsu People’s Hospital, including 538 patients with mild acute pancreatitis (MAP) and 461 patients with MSAP. MSAP patients were divided into four groups according to local complication and transient organ failure (TOF), including single acute peripancreatic fluid collection (APFC) without TOF group (group A), multiple APFC without TOF group (group B), other local complication without TOF group (group C) and TOF group (group D). The baseline data and the severity of AP among the four subgroups were compared. Meanwhile, the severity of disease between group A and MAP patients was also compared. Logistic regression analysis was used to evaluate the risk factors of MSAP. Results: Patients in group D were older than those in group A (P<0.05). There were statistically significant differences in different scoring systems among the four subgroups (P<0.05). The proportions of APACHE Ⅱ≥8, Glasgow≥3 and BISAP≥3 in group D were significantly higher than those in the other three groups (P<0.05). There were significant differences in levels of Ca