High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in DGAT and PDAT in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology. Furthermore, future research and application of DGAT and PDAT are prospected. This review aims to provide a basis for deeply understanding the molecular mechanism of plant oil synthesis and improving the quality and productivity of oil crops by the utilization of DGAT and PDAT genes.
Diacylglycerol O-Acyltransferase/physiology* ; Plant Oils/metabolism* ; Acyltransferases/metabolism* ; Lipid Metabolism/genetics* ; Gene Expression Regulation, Plant ; Triglycerides/biosynthesis*

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

Objective: To constructCSF1R+/-mice and to analyze their genotypes, so as to provide animal model basis for disease pathological mechanism and drug target. Methods : A linearized targeting vector was designed according to Cre/Loxp system. A Loxp site was inserted upstream of the 5th exon of theCSF1Rgene, and a neomycin resistance box with Loxp sites on both sides was inserted downstream of the 5th exon. The linearized targeting vector was electroporated into embryonic stem cells. The correctly targeted embryonic stem cells were injected into the blastocysts of C57BL/6J mice to obtain chimeric mice, which were bred with Zp3-Cre mice. The newborn mice were numbered 9-14 days after birth and their tails were cut. The DNA of the mice was extracted, and the genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. The expression of CSF1R in mouse macrophages was detected by flow cytometry. The expression of CSF1R in mouse tissues was detected by Western blot. Results: The results of agarose gel electrophoresis showed that 453 bp bands were amplified in wild type mice, and 453 bp and 650 bp bands were amplified in heterozygous mice. The results of flow cytometry showed that the expression of CSF1R in peritoneal macrophages and bone marrow-derived macrophages of CSF1R heterozygous mice was lower than that of WT group(P<0.05). The results of Western blot showed that the expression of CSF1R in spleen, kidney and brain tissue of CSF1R heterozygous group was lower than that of WT group(P<0.05). Conclusion CSF1R+/-mice are successfully constructed, reproduced and identified, which provides an animal model basis for further revealing the potential mechanism of CSF1R in immune regulation.

Objective:To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer.Methods:This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded.Results:All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient.Conclusions:The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

Objective To explore the protective effect and mechanism of modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on diabetic kidney disease(DKD)mice based on the regulation of VEGF-C/VEGFR3 pathway inhibiting lymphangiogenesis.Methods Twenty-four male db/db mice were randomly divided into model group,Chinese medicine group(modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction,crude drug 24.44 g·kg-1)and western medicine group(Irbesartan,13.5 mg·kg-1),with eight mice in each group.Eight db/m mice were selected as control group.Intragastric administration was given once a day for 12 consecutive weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),urinary albumin/creatinine ratio(ACR)and kidney index were measured.The pathological changes of renal tissue were observed by HE and Masson staining.The expressions of fibronectin(FN),type I collagen(Col I),Vimentin,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor receptor 3(VEGFR3),vascular endothelial growth factor-C(VEGF-C),lymphatic endothelial hyaluronic acid receptor 1(LYVE-1),podoplanin(PDPN),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in renal tissue were detected by immunohistochemistry.The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were detected by Western Blot.The mRNA expressions of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were detected by Real-time PCR.Results Compared with the control group,the levels of serum FBG,TG,TC,ACR and kidney index in the model group were significantly increased(P＜0.05).Glomerular hypertrophy,mesangial matrix increased,basement membrane thickening,cystic cavity narrowing,renal tubular epithelial cell degeneration and necrosis,interstitial infiltration of a large number of inflammatory cells,renal tubular atrophy;the level of renal fibrosis was significantly increased(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the expression of VEGF-C protein in cytoplasm and the expression of VEGFR3 and PDPN protein around renal tubular capillaries were significantly up-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly up-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly increased(P＜0.05).Compared with the model group,the levels of serum TG,TC and ACR in the Chinese medicine group were significantly decreased(P＜0.05).Renal tissue injury was improved to varying degrees,renal inflammatory cell infiltration was reduced to a certain extent,and renal tissue fibrosis was significantly reduced(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the protein expression of VEGF-C in cytoplasm and the protein expressions of VEGFR3 and PDPN around renal tubular capillaries were significantly down-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly down-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly decreased(P＜0.05).Conclusion Modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction can reduce the level of inflammation and fibrosis in renal tissue of DKD mice,and its mechanism may be related to the regulation of VEGF-C/VEGFR3 pathway to inhibit lymphangiogenesis.

Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for Cmax,99.64 to 103.62 percent for AUC0-tand 99.39 to 103.51 percent for AUC0-∞,respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for Cmax,100.37 to 104.51 percent for AUC0-tand 100.71 to 104.63 percent for AUC0-∞,respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of Cmax,AUC0-tand AUC0-∞ for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.

Objective To analyze the onset characteristics of type 2 diabetes mellitus (T2DM) with cognitive impairment in Baotou area, and study the improvement effect of GLP-1 receptor agonists. Methods A total of 320 patients with T2DM admitted between September 2021 and September 2022 were selected and divided into the observation group with T2DM and cognitive dysfunction and the negative control group without cognitive dysfunction according to their cognitive function status , Among the 160 cases in each group; Patients with type 2 diabetes and cognitive impairment were randomly divided into a treatment group and a control group, 80 cases in each group; the control group was treated with conventional treatment, and the treatment group was additionally treated with semaglutide; Logistics multiple regression model was used to analyze T2DM The related risk factors of cognitive impairment in patients were assessed by the Mini-Mental State Examination (MMSE) score to evaluate the cognitive function of the patients. Results Multivariate regression model showed that course of disease, age, vitamin D, HbA1c, LDL-C, BMI, Hcy, Lp-PLA2, TNF-α, IL-6 and folic acid levels were also independent risk factors for cognitive impairment in T2DM patients (P<0.05); There was a significant positive correlation between GLP-1 receptor agonists and cognitive function recovery in T2DM patients with cognitive impairment (P<0.05). Conclusion The onset of T2DM with cognitive impairment in Baotou area is often accompanied by a long course of disease, older age, abnormal levels of vitamin D, HbA1c, LDL-C, BMI, Hcy, Lp-PLA2, TNF-α, IL-6 and folic acid, and GLP -1 receptor agonists have a clear role in improving the cognitive function of patients.

ObjectiveTo analyze the effect of different fixation methods on the chemical quality characteristics and antioxidant activity of Rehmannia glutinosa leaves， so as to lay a foundation for the selection of processing technology and quality evaluation of this medicinal materials. MethodR. glutinosa leaves was dried at 55 ℃ after treating by three fixation methods （55 ℃， boiling water， 105 ℃）， and then the fingerprints of R. glutinosa leaves were collected by high performance liquid chromatography （HPLC） and near infrared spectroscopy （NIRS）， and their antioxidant activities were analyzed by the 2，2-biphenyl-1-picrylhydrazyl （DPPH） method. Finally， similarity analysis， principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA） and Pearson correlation analysis were used to comprehensively evaluate the quality of R. glutinosa leaves with different fixation methods. ResultThe results of HPLC and NIRS fingerprint analysis indicated that there were differences in the quality characteristics of R. glutinosa leaves by different fixation treatments. The comprehensive score of chemical quality of R. glutinosa leaves by fixation at 55 ℃ was the highest， its average comprehensive score was 2.096， followed by fixation at 105 ℃， and the lowest was fixation with boiling water. The antioxidant activity of sample with fixation at 55 ℃ was the highest， followed by fixation with boiling water. The results of OPLS-DA showed that verbascoside， isoacteoside and catalpol were the main components causing the difference in chemical quality of the leaves from the three treatments， and the three components were positively correlated with the antioxidant activity of R. glutinosa leaves. Among them， the correlation between verbascoside and antioxidant activity was extremely significant， and the isoacteoside was significant. ConclusionThe chemical quality and antioxidant activity of R. glutinosa leaves are affected by the method of fixation， and the fixation at low temperature is the best primary processing method of R. glutinosa leaves.

Objective: To systematically evaluate the relationship between neck circumference and hypertension of primary and secondary school students. Methods: Web of science, PubMed, Scopus, CNKI and WanFang databases were searched by computer, and the retrieval time was from inception to December 2019. Two researchers independently screened the literature, extracted the data and evaluated the quality, and then performed Meta-analysis using Stata 14.0 software. Results: A total of 8 studies were included, including 20 475 subjects. Meta-analysis results showed that the risk of hypertension increased by 35% in people with a high neck circumference compared with the normal population(OR=1.35, 95%CI=1.20-1.51, P<0.01). The results of subgroup analysis showed that the correlation between neck circumference and hypertension of obese primary and secondary school students was 1.41 times higher than that of normal weight students(OR=1.41, 95%CI=1.23-1.61, P<0.01). The correlation between the neck circumference and the risk of hypertension of primary and secondary school students in Europe and America was more significant than that in Asia(OR=1.31, 95%CI=1.11-1.53, P=0.01). When the mean value of neck circumference was greater than 28.5 cm(OR=1.29, 95%CI=1.02-1.64, P=0.03), it was associated with the incidence of hypertension. Conclusion The neck circumference of primary and middle school students is related to the risk of hypertension, especially in obese people. Blood pressure monitoring and health education should be strengthened to prevent hypertension.