ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

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.

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 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.