Objective:To investigate the value of anlotinib combined with radiotherapy in second-line targeted drug-resistant advanced lung adenocarcinoma with epidermal growth factor receptor(EGFR) mutation.Methods:A total of 150 patients with advanced lung adenocarcinoma with EGFR mutation who were resistant to second-line targeted therapy and admitted to the Affiliated Hospital of Shaoxing University from July 2021 to July 2023 were prospectively selected as the study objects, and they were divided into the control group and the study group by random number table method, with 75 cases in each group. The control group received radiotherapy, and the study group received anrotinib combined radiotherapy. The recent clinical effects, tumor indexes, cellular immune indexes and the occurrence of adverse reactions were compared between the two groups.Results:After treatment, the objective response rate (ORR) and disease control rate (DCR) in the study group were higher than those in the control group: 53.33%(40/75) vs. 34.67%(26/75), 86.67%(65/75) vs. 64.00%(48/75), there were statistical differences ( χ2 = 5.30, 10.37, P<0.05). After treatment, the levels of VEGF, cytokeratin 21-1 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in the study group were lower than those in the control group: (472.93 ± 45.71) ng/L vs. (510.26 ± 50.49) ng/L, (4.82 ± 1.13) μg/L vs. (5.25 ± 1.34) μg/L, (5.65 ± 1.24) μg/L vs. (6.17 ± 1.42) μg/L, there were statistical differences ( P<0.05). After treatment, the levels of CD 3+, CD 4+ and CD 4+/CD 8+ in the study group were higher than those in the control group, and the level of CD 8+ was lower than that in the control group: 0.532 ± 0.044 vs. 0.508 ± 0.041, 0.321 ± 0.030 vs. 0.305 ± 0.027, 1.02 ± 0.19 vs. 0.93 ± 0.16, 0.303 ± 0.040 vs. 0.320 ± 0.044, there were statistical differences ( P<0.05). There was no significant difference in the occurrence of adverse reactions between the two groups ( P>0.05). Conclusions:Anlotinib combined with radiotherapy can enhance the clinical efficacy of second-line targeted drug resistant advanced lung adenocarcinoma with EGFR mutation, improve tumor indexes, promote the recovery of immune function, without significantly increasing adverse reactions.

AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ²_trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.

Objective:To investigate the effects of the expanded lateral thoracic artery perforator flap in the reconstruction of breast scar contracture deformity after burns in minor females.Methods:The study was a retrospective observational study. From July 2018 to October 2023, 8 female children aged 4 to 12 years and with breast scar contracture deformity after burns, who met the inclusion criteria, were admitted to the Department of Burns and Plastic Surgery of Guangzhou Red Cross Hospital of Jinan University. The skin and soft tissue expander (hereinafter referred to as expander) was placed in the first stage. The contracture scar was removed and released in the second stage, and the wound formed after the scar was removed measured between 9 cm×8 cm and 15 cm×10 cm. The expanded lateral thoracic artery perforator flap was designed and transferred to repair the wound with resected flap area of 10 cm×9 cm to 16 cm×11 cm, and the wound at the flap donor area was directly sutured. The complications such as incision infection, hematoma, and expander exposure were observed after stage Ⅰ surgery. After stage Ⅱ surgery, the survival of the flap and the wound healing at the flap donor area were observed. During the 1-year follow-up after the stage Ⅱ surgery, the breast development was evaluated according to tanner staging performance of female pubertal breast development, the aesthetic effect of the affected breast was evaluated by using the aesthetic effect evaluation standard after breast surgery, the Vancouver scar scale (VSS) was used to score the scar condition at the flap donor and recipient areas, and the satisfaction of the children's families with the surgical outcomes was investigated by using a self-made scale.Results:After stage Ⅰ surgery, no incision infection, hematoma, expander exposure, or other complications occurred in 8 children. After stage Ⅱ surgery, only one child had tissue necrosis at the distal end of the flap with a size of about 2 cm×1 cm, which healed after dressing change, and the flap in other children had good blood supply, soft texture, moderate thickness, and similar color to the skin at the recipient area. The wounds at all flap donor areas healed well. During the 1-year follow-up after stage Ⅱ surgery, 7 children had normal breast development, with their breast volume, height, and shape being almost the same as or similar to the healthy side, with the aesthetic effect of all being grade Ⅰ; the breast in one child had not yet developed, and these indicators were not evaluated. The locations of nipple areola complex in 8 children were almost the same as or similar to those in the healthy side, and their skin color, integrity, texture, and elasticity of the partial breast repaired by the transferred flap were similar to those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The shapes of nipple and areola in 5 children were inconsistent with those in the healthy side because of the original scar, with the aesthetic effect of all being grade Ⅱ, and the shapes of nipple and areola in the other 3 children were consistent with those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The VSS score of the scar at the flap recipient area was 2-5, and the VSS score of the scar at the flap donor area was 1-3. Seven children's families were satisfied with the surgical effect, and one child's family was basically satisfied with the surgical effect.Conclusions:For the breast scar contracture deformity of minor females after burns, the expanded lateral thoracic artery perforator flap is used for reconstruction before puberty, which results in fewer postoperative complications, good breast shape, and hidden scar at the flap donor area. It is beneficial for the normal development of adolescent breasts, and is one of the safe and effective methods for the treatment of breast scar contracture deformity in minor females after burns.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.