Objective:To investigate the effect of dexmedetomidine (DEX) on intestinal barrier function impairment in gynecologic neoplasms patients undergoing laparoscopic surgery and the possible role of silent information regulator 1 (SIRT1) in this process.Methods:A prospective randomized controlled study was conducted. Forty patients who were to undergo laparoscopic surgery of gynecologic neoplasms under general anesthesia in the Second Hospital of Shanxi Medical University from May 2022 to May 2023 were prospectively selected. All patients were divided into the experimental group and the control group using the method of randomized numerical table, with 20 cases in each group. The experimental group was given a loading dose of DEX 0.5 μg/kg (intravenously pumped in 10 min) before induction of general anesthesia, and then maintained with DEX 0.2 μg·kg -1·h -1 until 30 min before the end of surgery. In the control group, the same dose of 0.9% sodium chloride injection was pumped intravenously. Taking 5 ml of peripheral venous blood from the upper extremities 10 min before induction of anesthesia (T 1), 1 h after the release of pneumoperitoneum (T 2) and 24 h after the release of pneumoperitoneum (T 3), respectively, the serum levels of SIRT1 and Claudin-1 proteins were measured by enzyme-linked immunosorbent assay. Then the concentrations of SIRT1 and Claudin-1 proteins and the time of first postoperative exhaust in the two groups of patients were compared. Results:The differences in age, body mass index, pneumoperitoneum time, operation time and anesthesia time between the two groups were not statistically significant (all P >0.05). At T 1, there was no statistically significant difference in concentrations of SIRT1 [(10.2±1.5) ng/ml vs. (10.0±1.3) ng/ml, t = 0.46, P = 0.468] and Claudin-1 [(405±45) pg/ml vs. (404±40) pg/ml, t = 0.13, P = 0.901] proteins between the control group and the experimental group. At T 2, the concentrations of SIRT1 [(8.4±1.3) ng/ml vs. (6.1±1.3) ng/ml, t=-5.55, P<0.001] and Claudin-1 [(383±39) pg/ml vs. (331±44) pg/ml, t=-4.02, P<0.001] proteins in the experimental group were higher than those in the control group, the differences were statistically significant. At T 3, the concentrations of SIRT1 [(8.4±1.2) ng/ml vs. (6.7±1.1) ng/ml, t=-4.56, P<0.001] and Claudin-1 [(388±40) pg/ml vs. (341±43) pg/ml, t=-3.63, P<0.001] proteins in the experimental group were higher than those in the control group, the differences were statistically significant. The time of first postoperative exhaust in the experimental group was shorter than that in the control group [(21.7±2.2) h vs. (27.9±3.4) h], and the difference was statistically significant ( t =6.78, P < 0.001). Conclusions:Dexmedetomidine may reduce the intestinal epithelial cell injury induced by laparoscopic surgery in patients with gynecologic neoplasms via activating SIRT1, and exert a protective effect on intestinal barrier function.

Objective:To investigate whether intestinal rehabilitation therapy (IRT)could optimize the effectiveness of IRT in patients with short bowel syndrome (SBS) caused by acute mesenteric ischemia (AMI) with chronic multivessel lesions.Methods:Clinical data of 18 hospitalized patients diagnosed with AMI leading to SBS and undergoing IRT at the Eastern Theater General Hospital of the People's Liberation Army from Jan 2012 to Oct 2023 was retrospectively analyzed.Result:Following IRT, the revascularization group showed significantly greater increases in ASMI and grip strength compared to the control group [(0.28±0.26) kg/m 2vs. (0.02±0.21) kg/m 2, P=0.033, and (0.97±0.33) kg vs. (0.48±0.34) kg, P=0.007, respectively]. Similarly, the increase in EN intake was significantly higher in the revascularization group compared to the control group [(572.5±93.6) ml/d vs. (375.2±176.3) ml/d, P=0.012], accompanied by a greater improvement in intestinal nitrogen absorption rate [(25.06±14.06)% vs. (13.84±4.62)%, P=0.034] and a more substantial decrease in GSRS scores [(-15.88±3.94) vs. (-6.33±5.13), P=0.030]. Moreover, there were significant differences in the composition of EN formulations between the two groups after IRT ( P=0.046). Additionally, SF-36 scores at discharge were significantly higher in the revascularization group than that in the control group for five indicators including BP, GH, VT, SF, and MH ( P<0.05). Conclusions:For patients with SBS resulting from AMI by chronic multivessel lesions, revascularization therapy may not leading to higher growth in weight and hematological nutritional indicators during IRT, but it is beneficial for improving muscle function, improving EN absorption, increasing the likelihood of PN independence, relieving gastrointestinal symptoms, and enhancing overall quality of life.

Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:To investigate the role of dietary fiber in the intestinal rehabilitation for patients with ultra-short bowel syndrome.Methods:This study included 34 inpatients diagnosed with ultra-short bowel syndrome in the General Surgery Department of the Eastern Theater General Hospital of the People's Liberation Army from January 2012 to October 2023. Patients were grouped based on whether they received intestinal rehabilitation and whether dietary fiber was added to the treatment plan, and were divided into three groups: nutritional therapy group (11 cases), growth hormone + glutamine intestinal rehabilitation treatment group (10 cases) and growth hormone injection + glutamine + dietary fiber intestinal rehabilitation treatment group (13 cases). The therapeutic regimen and its changes, pre- and post-treatment parameters of hematology, nutrition, intestinal absorption, fecal consistency, and quality of life were recorded and compared, and the impact of different treatment regimens on clinical outcomes was analyzed.Results:Compared with nutrition treatment group and growth hormone + glutamine intestinal rehabilitation treatment group, growth hormone injection + glutamine + dietary fiber intestinal rehabilitation treatment group, the increase of enteral nutritional fluid, the decrease of parenteral nutritional energy, the increase of intestinal moisture absorption, the decrease of defecation times and the appreciation of hemoglobin were significantly increased, and the difference was statistically significant ( P<0.05). At the same time, the levels of insulin-like growth factor 1 and insulin-like growth factor binding protein were significantly increased after treatment ( P<0.01). Conclusions:Nutritional support combined with intestinal rehabilitation can significantly improve the nutritional status and intestinal absorption rate of ultra-short bowel syndrome patients. The use of dietary fiber in the intestinal rehabilitation regimen for ultra-short bowel syndrome patients yields more significant benefits, as evidenced by improved clinical outcomes.

Objective:To investigate the effect of vitamin D supplementation on weight loss efficacy and insulin resistance (IR) in obese patients.Methods:It was a randomized controlled trial. A total of 190 obese patients with vitamin D deficiency were selected from the obesity clinic of Tianjin Union Medical Center from March to December in 2023. The patients were divided into control group (95 cases) and vitamin D group (95 cases) according to random number table. The control group was given energy-limited high-protein diet combined with moderate intensity exercise, and the vitamin D group was supplemented with vitamin D on the basis of the control group, 14 000 U/week for 24 weeks. A total of 25 dropped out of the study from the two groups for various reasons. Finally, 79 cases in the control group and 86 cases in the vitamin D group were included in the analysis. Independent sample t test and rank sum test were used to compare serum 25 hydroxyvitamin D [25 (OH) D] level, body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin and glycated hemoglobin (HbA 1c) between the two groups at baseline and after intervention. Homeostasis model insulin resistance index (HOMA-IR) was used to evaluate the degree of insulin resistance (IR), and the effects of vitamin D supplementation on weight loss efficiency and IR in those patients were analyzed. Results:There was no significant differences in serum 25(OH)D level between the two groups before intervention ( P>0.05); the serum 25(OH)D level in the vitamin D group was significantly higher than that in the control group after intervention [(30.90±7.55) vs (16.00±4.34) μg/L] ( t=-15.35, P<0.001). The body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin, HbA 1c, and HOMA-IR were all significantly lower after the intervention than those before the intervention in both groups [control group: (93.32±13.47) vs (98.95±14.31) kg, (33.74±5.09) vs (35.80±5.52) kg/m 2, (39.77±11.87) vs (44.12±12.79) kg, (183.76±40.95) vs (204.01±32.18) m 2, 5.00 (4.55, 5.67) vs 5.24 (4.68, 6.42) mmol/L, 16.78 (13.94, 24.30) vs 22.56 (15.95, 31.2) mU/L, 5.55%±0.53% vs 6.05%±0.99%, 4.11 (3.14, 5.57) vs 5.51 (3.61, 8.49); vitamin D group: (88.14±17.66) vs (104.43±22.02) kg, (31.02±5.10) vs (36.66±5.98) kg/m 2, (35.51±12.87) vs (46.67±13.33) kg, (166.50±49.50) vs (213.64±40.14) m 2, 4.70 (4.35, 5.07) vs 5.17 (4.77, 6.30) mmol/L, 13.18 (9.87, 18.84) vs 21.67 (15.78. 32.74) mU/L, 5.43%±0.48% vs 6.21%±1.22%, 2.88 (1.99, 4.21) vs 5.19 (3.82, 9.27)], and the body weight, body mass index, adiposity, visceral fat area, fasting blood glucose, fasting insulin, and HOMA-IR were all significantly lower in vitamin D group than those in the control group [(88.14±17.66) vs (93.32±13.47) kg, (31.02±5.10) vs (33.74±5.09) kg/m 2, (35.51±12.87) vs (39.77±11.87) kg, (166.50±49.50) vs (183.76±40.95) m 2, 4.70 (4.35, 5.07) vs 5.00 (4.55, 5.67) mmol/L, 13.18 (9.87, 18.84) vs 16.78 (13.94, 24.30) mU/L, and 2.88 (1.99, 4.21) vs 4.11 (3.14, 5.57), respectivley] (all P<0.05). The IR remission rate was significantly higher in the vitamin D group than that in the control group after the intervention (37.3% vs 15.3%) ( χ2=8.071, P=0.002). Conclusion:Supplementation of vitamin D on the basis of energy-limited high-protein diet combined with moderate intensity exercise can significantly improve the efficacy of weight loss and IR in obese patients with vitamin D deficiency.

The ApoE gene is a genetic risk determinant for sporadic Alzheimer′s disease (AD). The ApoEε4 allele increases the risk of developing AD relative to the common ApoEε3 allele, whereas the ApoEε2 allele decreases the risk of developing the disease. The 3 alleles encode ApoE2, ApoE3, and ApoE4 protein isoforms, respectively. ApoE4 contributes to the pathogenesis of AD by regulating β-amyloid protein, tau protein, transactive response DNA-binding protein-43, neuroinflammation, and cerebral vascular function. The pathways associated with ApoE also offer new opportunities for the treatment of AD. In addition, studies have shown that ApoE4 also plays a toxic role in other neurological disorders. This article described the biological characteristics of ApoE, as well as the impact of ApoE4 on AD and related dementias, aiming to enhance clinical doctors′ understanding of the involvement of ApoE4 in the pathogenesis of AD and related dementia.

OBJECTIVE To clarify the core content of traditional Chinese medicine （TCM） policy in the provinces of China， so as to provide reference for optimizing the structure of the policy system of traditional Chinese medicine in China and assisting the inheritance and innovation of TCM industry in various regions. METHODS The websites of directly affiliated organs in 31 provinces， excluding Hong Kong， Macao and Taiwan， were retrieved to collect the TCM policies released from 2000 to 2021. The importance of keywords in the TCM policies of each province was measured based on term frequency-inverse documentation frequency （TF-IDF） keyword extraction method， and the similarities and differences were analyzed among TCM policies. RESULTS & CONCLUSIONS A total of 99 documents related to TCM policies of various provinces were obtained in this study， most of which were released after 2016. The theme of national TCM policy covered four aspects： building TCM talent team， perfecting TCM service system， strengthening TCM resource management and promoting TCM industry innovation. The TF-IDF values of “medical institutions”“traditional Chinese medicine”“medical treatment” were higher than other keywords in each province， indicating that the provinces paid more attention to the construction of TCM service system and the management of TCM resources than other aspects. Anhui and Jiangsu， Beijing and Henan， Hubei and Jilin， Hubei and Tianjin， and Hubei and Yunnan had the more degree of similarity in TCM policies， which all contained 16 of the same keywords. Therefore， the above regions should be encouraged to strengthen exchanges and cooperation and realize mutual promotion and joint development. Among all the keywords whose importance ratio was greater than 0.2，“ Tibetan medicine” was unique to Qinghai and Tibet，“ disease type” was unique to Guangdong， and the TF-IDF value of “supervision and management” in Beijing was higher， indicating that the emphasis of TCM policy formulation in different provinces was various. Meanwhile， the top 10 keywords of TF- IDF value in all provinces did not have words related to financial input， and the TF-IDF values of “informatization” in most provinces did not rank at the top. It is suggested to increase financial input or encourage social financing， and add “Internet+new business” in the field of TCM.

Objective:To investigate the effectiveness of a tiered progressive training model in the standardized residency training of general practice in primary care institutions.Methods:A tiered progression teaching plan was applied for 26 general practice residents who attended the rotation of general practice residency training in Beijing Fangzhuang Community Hearlth Service Center from June 2022 to May 2023. The plan defined the teaching objectives and requirements for different stages, and the Leicester Assessment Package (LAP) and narrative medicine were included in the teaching methods. The effectiveness of the tiered progression training was evaluated through a questionnaire survey on the post competency of general practice residents.Results:There were 12 primary stage residents, 9 intermediate stage residents and 5 advanced stage residents. The post-training scores of general practice residents in all three stages of residents were significantly higher than the pre-training scores ( t=-3.627,-2.073,-5.277,all P<0.05). The scores of basic medical and health services, basic public health services, information utilization ability and management ability, medical knowledge and lifelong learning, interpersonal communication and teamwork, professional quality after six post competency training were significantly higher than those before training in all three stages of residents. The scores of basic medical and health services, basic public health services, medical knowledge and lifelong learning, in primary residents were significantly improved compared with those before training ( t=-3.457,-3.428,-3.063, all P<0.05);the scores of basic public health services, interpersonal communication and teamwork, and professional quality in intermediate residents were significantly higher than those before training ( t=-2.328,-2.100,-1.997, all P<0.05); the scores of basic medical and health services, basic public health services, information utilization ability and management ability, medical knowledge and lifelong learning, interpersonal communication and teamwork, and professional quality in senior residents were significantly higher than those before training ( t=-5.707,-4.542,-2.952,-1.753,-2.705,-2.805, all P<0.05). Conclusion:The application of tiered and progressive training model in the standardized residency training is helpful to improve the post competency of general practice residents.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.