ObjectiveTo investigate the effects of prostaglandin E₂ （PGE₂） microinjection into the median preoptic nucleus （MnPO） on core body temperature in female mice， and to clarify its underlying mechanism. MethodsMicroinjection cannula were implanted into the MnPO of female mice using stereotaxic surgery.Subsequently， a multi-channel temperature acquisition system was used to simultaneously monitor rectal and brown adipose tissue （BAT） temperatures before and after intra-MnPO injections of different reagents.To investigate the thermoregulatory effects of the microinjection of PGE₂ into the MnPO， 12 female C57BL/6 mice were randomly divided into a saline group （n=6） and a PGE₂ group （n=6）， which were injected with 0.1 μL saline and PGE₂ （2.8 mmol/L）， respectively.To determine whether E-series prostaglandin receptor （EP）1， EP3， and EP4 receptors mediate the thermoregulatory effects of PGE₂， 15 female C57BL/6 mice were randomly divided into 3 groups （n=5 per group）.Mice in each group first received an injection of 0.1 μL PGE2 （2.8 mmol/L） into the MnPO. After their body temperature returned to baseline levels， they were subsequently injected with a mixture of either EP1， EP3 or EP4 antagonist （ant） （20 mmol/L） + PGE2 （2.8 mmol/L）. ResultsCompared with baseline level， the rectal temperature （P<0.01） and BAT temperature （P<0.001） of female mice both increased significantly after microinjection of PGE₂ into the MnPO.Compared with the saline group， the increases in rectal temperature （P<0.001） and BAT temperature （P<0.000 1） were significantly greater in the PGE₂ group of mice.Furthermore， following the injection of PGE₂ into MnPO， the increase in BAT temperature was found to be significantly greater than that in rectal temperature in mice （P<0.001）.Compared to the administration of PGE₂ alone， co-injection of an EP3 ant + PGE₂ into the MnPO of mice resulted in a significantly smaller increase in both rectal temperature （P<0.001） and BAT temperature （P<0.001）.In contrast， the increases in rectal and BAT temperatures following MnPO injection of either EP1 ant + PGE₂ or EP4 ant + PGE₂ were not statistically significant （P>0.05）. ConclusionInjection of PGE₂ into the MnPO elevates BAT and core body temperature in female mice via the EP3 receptor.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To investigate the diagnostic features of eosinophilic gastroenteritis (EGE) of the stomach and duodenum.Methods:A case-control study was conducted to retrospectively analyze 238 biopsy specimens of gastric and duodenal EGE (75 cases) and 133 biopsy specimens of chronic active gastroenteritis (97 cases) in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China from 2012 to 2023. The eosinophil count, infiltration site and other pathological features (e.g., infiltration of neutrophils into the epithelium, edema, and increase of background lymphocytes and plasma cells) were examined under a microscope. Chi-square test, chi-square multiple comparison ( Bonferroni method) and modified Poisson regression were used to analyze the data. Results:The results showed that there were significant differences in eosinophil count ( χ2=43.926, P<0.01), location ( χ2=31.391, P<0.01), neutrophilic infiltration of the epithelium ( χ2=5.199, P=0.023), edema ( χ2=3.934, P=0.047), and lymphoplasmacytosis ( χ2=36.813, P<0.01) between the EGE and control cases. The results of Chi-square multiple comparisons showed that eosinophils distributed in clusters or sheets (versus other grades of eosinophil presence) were statistically associated with EGE. When eosinophils infiltrated the epithelium (versus eosinophils in other locations of the mucosa), there was a statistically significant association with EGE. Modified Poisson regression also showed that EGE was more likely to have eosinophilic infiltration of epithelium [ RR=1.661, P=0.001,95% CI (1.397,1.973)] and that of muscularis mucosa [ RR=1.818, P<0.01,95% CI (1.491,2.216)]. Conclusions:The important pathological features for diagnosing EGE of the stomach and duodenum are that eosinophils are clustered or distributed in sheets with epithelial infiltration. However, epithelial infiltration by neutrophils, edema and background lymphoplasmacytosis are relatively rare.

Objective To investigate the bidirectional causal relationship between circulating amino acid levels and the risk of myasthenia gravis(MG)using Mendelian randomization(MR).Methods A two-sample Mendelian randomization a-nalysis was conducted using publicly available genome-wide association study(GWAS)genetic data,with validation from GWAS data from different sources to assess the robustness of the results.Five models were used for the two-sample bidirectional MR anal-ysis,and odds ratios(OR)were calculated to evaluate the causal relationship between the levels of nine circulating amino acids and MG risk.Sensitivity analyses,heterogeneity tests,and pleiotropy tests were performed to assess the robustness of the results.The causal effect estimated by the inverse variance weighted(IVW)method was the primary result,and the IVW-estimated causal effects were further validated using data from different GWAS sources to assess robustness.Results Genetically predicted high-er circulating glutamine levels were significantly associated with a lower risk of MG[OR(95％CI)=0.696(0.524,0.926),P=0.012 7,IVW model].Validation analyses using GWAS data from various sources also demonstrated a significant negative associa-tion between genetically predicted higher circulating glutamine levels and MG risk[OR(95％CI)=0.321(0.178,0.581),P=1.67x10-1,IVW model].Moreover,genetically predicted higher MG risk was associated with lower levels of circulating glutamine and alanine(β=-0.178±0.009,P=0.049;β=-0.013±0.007,P=0.048,IVW model,respectively).Conclusion Genetic evidence reveals a potential bidirectional causal relationship between circulating amino acid levels and MG risk.Further studies are required to elucidate the mechanisms underlying this relationship.

Differentiated thyroid cancer (DTC) is prone to central lymph node metastasis. Current guidelines and consensus explicitly state that the central lymph node range for thyroid cancer includes regions Ⅵ and Ⅶ. However,there is still controversy regarding the implementation of prophylactic central lymph node dissection(pCND) in DTC patients who have no lymph node metastasis detected by preoperative clinical examination and intraoperative exploration. Although the role of pCND in long-term survival,recurrence rate,and postoperative thyroglobulin levels in cN0 DTC patients remains unclear,it can effectively remove potentially metastatic lymph nodes in the central area. This not only helps to enhance the thoroughness of the surgery but also reduces the potential complications of reoperation. According to the “Diagnosis and treatment guidelines for thyroid nodules and differentiated thyroid cancer(second edition)” from 2023 and the general opinion of domestic scholars, it is recommended to perform pCND on the same side as the lesion for cN0 DTC patients. When performing pCND, it is crucial to maintain the accuracy of the surgical scope to minimize the risk of postoperative complications.

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.