Objective:To analyze the effect of donepezil hydrochloride combined with memantine on cognitive function in patients with Alzheimer's disease (AD).Methods:A randomized controlled trial was conducted among 90 patients with AD who were treated at the Zaozhuang Mental Health Center from January 2021 to March 2023. The patients were divided into a donepezil group and a combination group using a random number table grouping method, with 45 patients in each group. The donepezil hydrochloride group received only oral administration of donepezil hydrochloride tablets, while the combination group received oral administration of both donepezil hydrochloride tablets and memantine tablets. The two groups were continuously treated for 12 weeks. Before and after treatment, the Activities of Daily Living scale (ADL) score, the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score, the Mini-Mental State Scale (MMSE) score, and biochemical indicators (homocysteine, neuron-specific enolase, and S100 β) were compared between the two groups. Adverse drug reactions were observed in each group.Results:After treatment, the ADL, BEHAVE-AD, and MMSE scores in the combination group were (78.9 ± 6.1) points, (5.2 ± 0.5) points, and (22.8 ± 2.2) points, respectively, and they were (65.2 ± 5.9) points, (9.6 ± 0.9) points, and (19.4 ± 2.4) points, respectively, in the donepezil hydrochloride group. The ADL and MMSE scores in the combination group were significantly higher than those in the donepezil hydrochloride group ( t = 10.83, 7.01, both P < 0.001). The BEHAVE-AD score in the combination group was significantly lower than that in the donepezil hydrochloride group ( t = -28.67, P < 0.001). After treatment, serum levels of homocysteine, neuron-specific enolase, and S100 β in the combination group were (17.8 ± 3.6) μmol/L, (16.8 ± 2.7) μg/L, and (17.4 ± 7.5) μg/L, respectively, which were significantly lower than (21.5 ± 3.3) μmol/L, (20.4 ± 3.7) μg/L, and (23.5 ± 5.1) μg/L in the donepezil hydrochloride group ( t = -5.08, -5.27, -4.51, all P < 0.001). The incidence of adverse drug reactions in the combination group was 13.3% (6/45), which was slightly, but not significantly, higher than 8.9% (4/45) in the donepezil group ( χ2 = 0.45, P = 0.502). Conclusion:The combination of donepezil hydrochloride and memantine can effectively improve the mental and behavioral symptoms and cognitive function of patients with AD, improve daily living ability, and do not increase adverse reactions. The combined therapy has high clinical application value.

Objective:To investigate the relationship between non-alcoholic fatty liver disease(NAFLD) and hepatic fibrosis and skeletal muscle mass in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 685 T2DM patients diagnosed at the Endocrinology department of Lanzhou University First Hospital, from April 2022 to May 2023, were divided into NAFLD and Non-NAFLD groups, and the NAFLD group was further categorized into fibrosis and non-fibrosis based on aspartate aminotransferase(AST) /alanine aminotransferase(ALT) level. The differences in appendicular skeletal muscle mass(ASM), appendicular skeletal muscle mass index(ASMI), and the prevalence of muscle mass loss were compared across groups. The correlations between ASMI and NAFLD, as well as liver fibrosis were analyzed by binary logistic regression.Results:Among male T2DM patients, those with NAFLD had lower ASMI levels and a higher prevalence of muscle mass reduction compared to non-NAFLD group. Among female T2DM patients, those with NAFLD had lower levels of ASM and ASMI, and a higher prevalence of muscle mass reduction compared to non-NAFLD group. ASMI levels in both male and female T2DM patients were independently negatively correlated with NAFLD risk( OR=-0.696, 95% CI 0.579-0.837; OR=-0.757, 95% CI 0.629-0.911). In NAFLD patients, ASM and ASMI levels were lower in those with liver fibrosis compared to those without fibrosis; however, the prevalence of muscle mass reduction did not differ significantly. Among male NAFLD patients, ASMI levels were independently negatively correlated with the risk of liver fibrosis( OR=-0.726, 95% CI 0.537-0.983), while no correlation was found in female patients. Conclusion:Reduced muscle mass is independently associated with the risk of NAFLD in both male and female T2DM patients. In males, reduced muscle mass is also independently related to the risk of liver fibrosis.

Objective:To compare the differences in surgical safety and postoperative cosmetic effects between endoscopic nipple-sparing mastectomy with immediate prepectoral prosthesis breast reconstruction and conventional nipple-sparing mastectomy with immediate subpectoral prosthesis breast reconstruction.Methods:The clinical data of early breast cancer patients admitted to the Department of Breast Surgery of Peking University Peoples Hospital from Oct 1, 2022 to Sep 13, 2023 was retrospectively analyzed.Results:According to the surgical method, the patients were divided into endoscopic surgery group (30 cases) and traditional surgery group (46 cases). There were no significant differences in the basic clinicopathological data, and the number of sentinel lymph nodes taken and axillary lymph nodes dissected between the patients in two groups (all P>0.05). Compared with that in traditional surgery group, the patients in endoscopic surgery group had longer operation time and more wound drainage volumes 3 days after surgery (all P<0.05). There was no significant differences in the probability of postoperative complications between the patients in two groups (all P>0.05), however, the proportion of nipple-areola complex necrosis in patients of endoscopic surgery group (10.0%) was lower than that of traditional surgery group (26.1%). Conclusions:The single-port insufflation technique-assisted endoscopic nipple-sparing mastectomy with immediate prepectoral prosthesis breast reconstruction maximize the cosmetic effect. Under the premise of strict selection of indications, it can be an optional surgical method.

A 49-year-old female examinee, employed at a paper company in Guigang, Guangxi (engaged in the production of napkins), visited the Qintang District People′s Hospital in Guigang on June 11, 2023, to apply for a health certificate. Salmonella was isolated during a physical examination screening for enteric pathogens ( Salmonella, Shigella), and repeated use of empirical antibacterial drugs failed to eradicate the pathogen. A reference laboratory identified the two isolates as S. Kentucky ST198 by performing serotyping, drug resistance phenotyping, and whole genome sequencing. Based on the regional serotype database of Salmonella in China, a phylogenetic tree of S. Kentucky ST198 resistance genotypes was constructed, defining both isolated strains as high-level drug-resistant ST198.2-1 subclade clones. Following a multidisciplinary consultation and based on antimicrobial susceptibility test results, the treatment was adjusted to amoxicillin/clavulanate and azithromycin. On August 19, three consecutive negative test results confirmed the eradication of Salmonella Kentucky.

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
Animals ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species ; Tumor Suppressor Protein p53/genetics* ; Signal Transduction ; Liver ; Aging ; Cell Cycle Proteins ; Interleukin-6

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

Objective:To study the association of non-alcoholic fatty liver disease(NAFLD) and advanced liver fibrosis with osteoporosis in patients with type 2 diabetes mellitus(T2DM).Methods:Data was collected from 391 in-patients with type 2 diabetes mellitus(T2DM) from September 2019 to September 2020 at the Department of Endocrinology and Geriatric Medicine, Affiliated Huai′an First Hospital of Nanjing Medical University in this cross-sectional study. Participants were divided into T2DM with coexistent NAFLD(TCN) and with no NAFLD(TON) group via liver B-mode ultrasound.Also, the patients were divided into low and middle-high risk group via fibrosis index based on 4 factors index(FIB-4). Participant characteristics, laboratory results, and dual energy x-ray absorptiometry were obtained and analyzed. Multivariable logistic regression models were used to evaluate the association of NAFLD and advanced liver fibrosis with osteoporosis in T2DM. Interaction and stratified analyses were conducted according to age, sex, body mass index(BMI) and duration of diabetes(DD).Results:There was no significant difference in risk of osteoporosis and bone mineral density(BMD) loss between TCN and TON group(all P>0.05). After adjusting for age, sex, BMI, and DD, total hip BMD( β=-0.044, 95% CI -0.087--0.001, P=0.046) and lumbar L 1-L 4BMD( β=-0.044, 95% CI -0.087--0.002, P=0.044) were significantly reduced, and the risk of osteoporosis was significantly increased( OR=2.428, 95% CI 1.124-5.244, P=0.024) in FIB-4 middle-high risk group compared with low risk group. The subgroup analysis showed that overweight patients with T2DM had a significantly increased risk of osteoporosis( OR=4.240, 95% CI 1.637-10.987, interaction P=0.018) in FIB-4 middle-high risk group compared with low risk group. Conclusion:There was no significant difference in risk of osteoporosis and BMD loss between TCN and TON group. However, among T2DM patients who were overweight, NAFLD-related progressive liver fibrosis emerged as an independent risk factor for both BMD decline and the development of osteoporosis.

Objective To explore the relationship between serum iron(SI)metabolism and glucose and lipid metabolism in patients with type 2 diabetes mellitus(T2DM).Methods A total of 170 T2DM patients hospitalized in the Department of Endocrinology,Lanzhou University First Hospital from 2019 to 2021 were included.During the same period,30 healthy individuals from physical examination center were selected as the normal control(NC)group.Based on HbA1c control,T2DM patients were divided into subgroups with good blood glucose control(H1,HbA1c＜7%,n=39),poor glucose control(H2,7%＜HbA1c＜9%,n=63)and very poor glucose control(H3,HbA1c＞9%,n=68).According to the level of blood lipids,T2DM patients were divided into subgroups with normal blood lipids(L1,n=36)and high blood lipids(L2,n=134).Results Compared with NC group,age,SBP,DBP,BMI,serum ferritin(SF),FPG,FIns,HOMA-IR,TyG,TG,LDL-C and SUA increased inT2DM group(P＜0.05),while SI,TF,total iron binding capacity(TIBC),DI,HDL-C and eGFR decreased(P＜0.05).The levels of TF and TIBC in H3 subgroup were lower than those in H1 subgroup(P＜0.05).LDL-C of L2 subgroup was higher than that of L1 subgroup(P＜0.05),while HDL-C was lower than that of L1 subgroup(P＜0.05).Pearson correlation analysis showed that SF was positively correlated with HbA1c,TyG,TG and SUA(P＜0.05),and negatively correlated with HDL-C and eGFR(P＜0.05).TF was positively correlated with HDL-C and eGFR(P＜0.05),but negatively correlated with age,SBP,DBP,TyG and SUA(P＜0.05).Multiple linear regression analysis showed that SF and FPG were influencing factors for HbA1c in T2DM patients.Conclusion SI metabolism is closely related to glucose and lipid metabolism in T2DM patients.

Trimethylamine N-oxide (TMAO) is an intestinal flora metabolite produced in the liver by the oxidation of trimethylamine (TMA) by hepatic enzymes. Recently, it has been found that plasma TMAO levels play an important role in the development and progression of osteoporosis. This review has presented the physiological functions and metabolic processes of TMAO, and its effects on the development and progression of osteoporosis through oxidative stress and inflammation. Plasma TMAO levels are influenced by diet as well as medications, which provides a new perspective and target for the treatment and prevention of osteoporosis.

Sarcopenia is a disease characterized by a decrease in muscle mass and function that can induce adverse events such as falls, weakness, and death. The latest research shows that the use of many hypoglycemic drugs is associated with sarcopenia. Different types of hypoglycemic drugs may have different effects and mechanisms for the quality and function of skeletal muscle. In this paper, we review the research progress of the relationship between hypoglycemic drugs and sarcopenia and the molecular mechanism in recent years to provide a reference for the diagnosis and treatment prevention of sarcopenia in clinical areas.