ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

The number of patients with reduced blood volume due to haemorrhage, fractures, severe infections, extensive burns and tumours is increasing, and traditional blood products are no longer able to meet the increasing clinical demand. Therefore, plasma substitutes have become particularly important in fluid resuscitation, especially artificial colloidal solutions, which have a sustained volume expansion time and a good volume expansion effect, and can significantly improve the circulatory status of patients. This article aims to review the classification of artificial colloidal plasma substitutes and their research progress in clinical practice, in order provide a more rigorous, professional and standardized reference for medicine.

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

The faithful segregation of genetic material to daughter cells is a fundamental biological process and a prerequisite for autonomous construction of robustly self-replicating artificial cells.Artificial cells are mimic cell structures with part or whole functions of normal cells.The complexity of eukaryotic chromosome segregation machinery has limited its applications in the field of synthetic biology.In contrast,the plasmid segregation machineries employed by prokaryotes are relatively simple and can provide valuable approaches for the bottom-up construction of complex artificial cells.This review aimed to comprehensively analyze the origin species and working mechanism of three bacterial plasmid segregation systems,namely ParABS,ParMRC,and TubZRC systems.The current researches on plasmid segregation both in bacterial and artificial cellular systems were summarized,and the future directions of this field were also proposed.

The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

The theory of " Sui Qi Suo De" originates from Zhang Zhongjing's Jin Gui Yao Lue and has been further developed by later generations of practitioners, offering significant guidance for clinical practice. Myelodysplastic syndromes (MDS) are common malignant disorders of the hematopoietic system, characterized by high heterogeneity and progressive mutational changes. In Traditional Chinese Medicine (TCM), MDS falls under the category of "marrow toxin exhaustion". This article applies the theory of " Sui Qi Suo De" in TCM to analyze the pathophysiological changes during different stages of MDS. Specifically, it explores the precursor stage (focusing on health maintenance and prevention before illness, addressing the " Suo De" of "gradual decline of vital qi"), the low-risk stage (strengthening the spleen and kidneys, clearing toxic pathogens, addressing the " Suo De" of "weakened vital qi invaded by pathogens"), and the medium-to-high-risk stage (detoxifying and reinforcing the body, harmonizing physical and mental health, addressing the " Suo De" of "dominant pathogens and declining vital qi"). The goal is to provide new directions and theoretical insights for the TCM treatment of MDS.

Objective To investigate the characteristics and differences of congenital endowment in senile dementia population based on the theory of five circuits and six qi.Methods Based on the cross-sectional data of China Health and Retirement Longitudinal Survey(CHARLS)in 2018,the dementia status of the population aged 60 and above in China was evaluated by using the Mini-Mental State Examination(MMSE),and the five-circuit and six-qi features at birth in the senile dementia population were analyzed by descriptive statistics and Chi-square goodness-of-fit test.Results A total of 854 patients with senile dementia were included.The five-circuit and six-qi features at birth in the senile dementia population were as follows:most of them were born at the heavenly stem of Bing while the least at the heavenly stem of Ji and Geng(P＜0.001),most of them were born at the earthly branch of Wei while the least at the earthly branch of Zi(P＜0.001),most of them were born at the yearly circuit of excessive water circuit while the least at the yearly circuit of excessive gold circuit and deficient earth circuit(P＜0.001),and most of the patients were born at sitan of taiyin damp-earth and zaiquan of taiyang cold-water while the least at sitan of jueyin wind-wood and zaiquan of shaoyang ministerial fire;no statistically significant differences were found in the dominant qi and guest qi(P＞0.05);most of the patients were born in the year of combination of circuit and qi being Shunhua while the least in the year of combination of circuit and qi being same celestial correspondence(P＜0.001),and the patients born in the year of Shunhua usually were frequently distributed in heavenly-stem and earthly-branch year of Jiawu(P＜0.001).Conclusion There is a certain relationship between the congenital endowment at birth and the incidence of senile dementia in the population of senile dementia.The circuit-qi features at birth for the prevalence of senile dementia are the yearly circuit of excessive water circuit,sitan of taiyin damp-earth and zaiquan of taiyang cold-water,and the year of the combination of circuit and qi being Shunhua.The population born at the time with the above circuit-qi features are prone to suffer the injury of the kidneys,the heart,and the spleen,and then result into illness.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals