Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

A combined radiation-wound injury refers to a radiation injury combined with a traumatic wound, with the characteristics of repeated ulceration and a long and difficult healing process, which is a focus in the field of research on difficult-to-heal wounds. To research combined radiation-wound injuries, the establishment of animal models is a key part, and appropriate animal models are a guarantee of reliable experimental results. This review summarizes the current research progress on various animal models of combined radiation-wound injuries in terms of radiation types, animal species, and injury types and location, aiming to provide a scientific basis for establishing standardized animal models, studying injury mechanisms, and evaluating prevention and treatment efficacy for combined radiation-wound injuries.

Objective To investigate the effect of anti-Mullerian hormone(AMH)levels on the development potential of oocytes in patients with polycystic ovarian morphology(PCOM)complicated with infertility during in vitro fertilization-embryo transfer.Methods A total of 480 infertile patients who met the inclusion and exclusion criteria were selected(160 cases in control group,104 cases in PCOM group and 216 cases in PCOS group),AMH levels were compared among different groups.According to the serum AMH level(4.7ng/ml as normal value,＞4.7ng/ml as high value),both PCOM and PCOS patients were divided into normal AMH group and high AMH group.The differences of oocyte indexes and their correlation between different AMH levels in PCOM and PCOS patients were ana-lyzed.Results The basal androgen level in PCOS group was significantly higher than that in PCOM group(P＜0.01).The comparison of serum AMH value showed that the control group＜PCOM group＜PCOS group(P＜0.001).Laboratory indexes showed that the num-ber of mature oocytes,2PN,fertilization,D3 cleavage and total embryos in the high AMH group were significantly higher than those in the normal AMH group in PCOM and PCOS patients(P＜0.05).The AMH levels was positively correlated with the number of mature oo-cytes,2PN,fertilization,D3 cleavage and total embryos(P＜0.05).In the PCOS group,the number of dominant follicles,oocytes,high-quality embryos and available embryos in the high AMH group were significantly higher than those in the normal AMH group(P＜0.05),and the AMH levels was positively correlated with the number of dominant follicles,oocytes,high-quality embryos and available embryos(P＜0.05).However,there was no significant difference in the above indicators among different AMH levels in PCOM group(P＞0.05).Conclusion The serum AMH level of PCOM patients with infertility is higher than that of the control group,but lower than that of PCOS patients.PCOM patients with high AMH level can obtain better quality oocytes and more embryos,and increase the number of transplantation in patients with repeated transplantation failure,thereby improving the clinical pregnancy rate.

Objective:To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients.Methods:A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition.Results:① There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. ② On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (μg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. ③ The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). ④ The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). Conclusion:Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Objective To explore the clinical efficacy of escitalopram combined with multidisciplinary collaborative management model(MCMM)on adolescents with first-episode major depressive disorder(MDD).Methods Two hundred adolescents with first-episode MDD who admitted to Fuyang Third People's Hospital,Anhui Province,from January 2019 to November 2023,were selected as study participnts.They were randomly divided into a control group and a MCMM group.Both groups of patients received sertraline hydrochloride tablets and routine psychiatric care for 8 weeks.Additionally,the MCMM group received an MCMM intervention on this basis.The clinical efficacy of the interventions,pre-and post-treatment assessments included clinical scale data[Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),and Connor-Davidson Resilience Scale(CD-RISC)],inflammatory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)],neurotrophin factors[serotonin(5-hydroxytryptamine,5-HT)and glial cell-derived neurotrophic factor(GDNF)]were compared between the two groups.Results Before the intervention,there were no statistical differences in the clinical scale data,inflammatory factors and neurotrophic factors between the two groups(P＞0.05).After 8 weeks of intervention,the HAMD score,HAMA score,serum IL-1β,IL-6,TNF-α,5-HT,and GDNF levels significantly decreased compared with pre-intervention(P＜0.05),while the CD-RISC score significantly increased(P＜0.05).In addition,the MCMM group showed greater reductions in HAMD,HAMA,IL-1β,IL-6,TNF-α,5-HT,and GDNF levels and a greater increase in CD-RISC score compared to the control group(P＜0.05).Conclusion Compared with sertraline combined with routine care,MCMM significantly alleviates anxiety and depression,enhances psychological resilience,and reduces inflammation in MDD patients.

Objective To observe the value of intravascular ultrasound(IVUS)for assisting endovascular therapy for renal artery stenosis(RAS).Methods Thirty patients with RAS who underwent endovascular therapy were retrospectively analyzed.Parameters of renal artery and plaques in RAS segment measured with CT angiography(CTA)and IVUS before treatment were compared.Bland-Altman diagram was performed to evaluate the consistency of lumen cross-sectional stenosis rate and plaque eccentricity index between CTA and IVUS.The stent parameters measured with IVUS were recorded immediately after implantation of balloon-expandable covered stents.Results Before treatment,the minimum lumen diameter,lumen cross-sectional stenosis rate and stenotic segment length of IVUS were all larger,while maximum lumen diameter and lumen eccentricity index of IVUS were both smaller than those of CTA(all P＜0.05).No significant difference of plaque eccentricity index,plaque type nor stenosis distal remodeling was found between CTA and IVUS(all P＞0.05).The average difference between IVUS and CTA for evaluating lumen cross-sectional stenosis rate and plaque eccentricity index was-0.020(-0.096,0.050)and-0.020(-0.130,0.091),respectively.The consistency of IVUS and CTA for evaluating plaque eccentricity index was better than that of lumen cross-sectional stenosis rate.The stent symmetry,stent eccentricity index,stent expansion coefficient and stenosis coverage rate immediately after implantation measured with IVUS was(82.69±14.61)%,(1.54±9.16)%,(99.81±10.70)%and 100%,respectively.Among 30 cases,2 cases(2/30,6.67%)underwent postdilation since poor stent apposition.Conclusion IVUS could assist evaluating lumen and plaque parameters of stenotic renal arteries,guiding stent release and real-timely monitoring the effect of endovascular therapy.

Objective:To investigate the effect of oral immunotherapy with donor human milk on feeding tolerance in premature infants with very low birth weight.Methods:A total of 94 extremely low birth weight preterm infants admitted to the neonatal Intensive Care Unit of Cangzhou People's Hospital from August 2022 to February 2024 were selected, These infants were randomized at 1:1 into 2 groups (47 cases each) using random number method. The control group were given oral 0.9% sodium chloride (oral drip), while the experimental group were given donor human milk (oral drip). General information were collected, including gender, delivery method, twins or not, small for gestational age or not, birth weight, gestational age, intestinal feeding of dairy products, and so on. Total intestinal feeding time, length of hospital stay and feeding intolerance were compared between groups.Results:The total intestinal feeding time and length of hospital stay were significantly shorter in the experimental group compared with the control group ( P<0.05). The incidence of feeding intolerance in the experimental group was also lower than that in the control group ( P<0.05). Conclusion:Oral immunotherapy with donor human milk can improve the feeding tolerance in premature infants with very low birth weight and shorten the hospital stay.

Maternal separation is a kind of social deprivation in early life that has been shown to impede the learning and memory abilities of rodents(mainly rats or mice)in adulthood.Animal models of mother-infant separation are commonly used to study the manifestations and mechanisms of learning and memory impairment.In this paper,an animal model of maternal-infant separation and related mechanisms of maternal-infant separation that affect offspring's learning and memory are reviewed to provide a basis for subsequent research on maternal-infant separation.