ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

ObjectiveRecent studies have highlighted the critical role of NUDT19 in the initiation, progression, and prognosis of specific cancer types. However, its involvement in pan-cancer analysis has not been fully characterized. This study aims to systematically explore the expression patterns, clinical significance, and immune-related functions of NUDT19 in various cancer types through multi-omics analysis, further revealing its potential role in cancer, particularly its functional and therapeutic target value in leukemia. MethodsTo achieve this goal, various bioinformatics approaches were employed to evaluate the expression patterns, clinical significance, and immune-related functions of NUDT19 in tumors and normal tissues. Additionally, we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications. Using the single-cell analysis tool SingleCellBase, we explored the distribution of NUDT19 across different cell subpopulations in tumors. To validate these findings, qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines, and we established acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) to conduct NUDT19 knockdown and overexpression experiments, assessing its effects on leukemia cell proliferation, apoptosis, and invasion. ResultsPan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types, which was closely associated with poor prognosis, clinical staging, and diagnostic markers. Furthermore, NUDT19 was significantly correlated with tumor biomarkers, immune-related genes, and immune cell infiltration in different cancers. Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes. Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells, suggesting its potentially diverse functional roles in different cell subpopulations. qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines. In AML cell lines, NUDT19 knockdown led to reduced cell proliferation and invasion, with increased apoptosis, while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis. ConclusionThis study demonstrates the diverse roles of NUDT19 in various cancer types, with a particularly prominent functional role in leukemia. NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms. Our research highlights the potential of NUDT19 as a therapeutic target, particularly for targeted therapies in malignancies such as leukemia, with significant clinical application prospects.

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C₃₀₇₉H₄₉₇₃N₈₈₃O₉₃₃S₁₉. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To observe the effects of amyloid-β(Aβ)receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro.Methods Mouse primary astrocytes were cultured,and divided into control group,Aβ group,Aβ+0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group,Aβ+Fluspirilene group,Aβ+GFP-LV group,and Aβ+mPirB-LV group.The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene,respectively,to inhibit endogenous PirB receptor,or overexpressed PirB gene via lentivirus transfection and then treated with Aβ1-42 oligomers.The proliferation of astrocytes was observed by RTCA and EdU methods,and the mRNA expression levels of S-100 calcium-binding protein B(S-100β),Vimentin,Nestin and amyloid precursor protein(APP)associated with reactive astrogliosis of astrocytes were observed by real-time PCR,and the expression level of glial fibrillary acid protein(GFAP)was detected by Western-blotting.Results The results of RTCA monitoring showed that normalized cell index(NCI)values of each group decreased sharply after treatment,and then increased gradually and tended to be stable.The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group(P<0.05)compared with control group;Compared with Aβ group,cell proliferation activity in Aβ + 0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased(P<0.01 or P<0.001).The results of real-time PCR showed that compared with control group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ group were significantly increased(P<0.05);Compared with Aβ group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased(P<0.01);Compared with Aβ+GFP-LV group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ +mPirB-LV group were significantly increased(P<0.05).The results of Western blotting showed that compared with control group,the expression of GFAP in Aβ group was significantly increased(P<0.05);Compared with Aβ group,the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased(P<0.05).Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis,and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Retzius-sparing robot assisted radical prostatectomy (RS-RARP) can significantly improve the immediate urinary continence without increasing the positive rate of surgical margin.However, the learning curve is long, and fewer than 10% of the surgeons can master it.Therefore,we have optimized the procedures of RS-RARP, applying radical prostatectomy with retrograde release of neurovascular bundle to preserve it to the maximum extent.Urethral anastomosis can be performed with only one suture, which eliminates the need for Hem-o-lok and reduces subsequent complications.Our team routinely carries out this operation, and conlcudes that this surgical method can achieve good tumor control, good urinary continence, fast recovery of sexual function, few complications, and strong operability.This article details the key steps and operation experience of this technique.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Objective To compare the differences in virulence-related factor aspartate protease,biofilm formation,and gene expression among clinical isolates of Candida parapsilosis(C.parapsilosis).Methods Gene sequencing and microsatellite typing(MT)method were adopted to identify C.parapsilosis isolated from patients with clinical fungal infection.The production of secreted aspartate protease and biofilm formation ability of each strain were de-tected,and the expression of biofilm formation related-genes BCR1,EFG1,and HWP1,as well as aspartate prote-ase virulence genes SAPP1,SAPP2,SAPP3 were compared among the strains.Results A total of 8 clinically iso-lated C.parapsilosis strains were collected,all of which were identified as genotype Ⅰ.Based on microsatellite ty-ping results,8 clinical strains were divided into 4 microsatellite types.G1,G2,and G3 strains isolated from the urine,peripherally inserted central catheters(PICC),and blood of patient A were of different subtypes.J1,J2,J3,J4,and J5 strains were of the same type,and isolated from blood specimens of patient B at different periods.All 8 clinical strains could form biofilm,and their biofilm formation ability was higher than that of the standard strain of C.parapsilosis(ATCC 22019).G1,G3 and J5 strains had strong biofilm formation ability,J1,J2,J3,and J4 strains had moderate biofilm formation ability,and G2 strain had weak biofilm formation ability.All of the eight clinical isolates secreted aspartate protease,and their in vitro expression levels of the enzyme were higher than that of the standard strain(ATCC 22019).G3,G1,and G2 strains showed low,moderate,and high in vitro enzyme expression respectively,with statistical differences(all P＜0.05).Enzyme expressed moderately in J1 and J5 strains,and highly in J2,J3,and J4 strains.Difference between moderate and high expressions was statistically significant(P＜0.05).The expression levels of biofilm formation genes BCR1,EFG1,and HWP1 in various strains isolated from patients A and B increased.In strains isolated from patient A,the expression level of EFG1 gene in G1 strain was higher than that in G2 strain(P＜0.05).There was no statistically significant difference in BCR1,EFG1,and HWP1 gene expression levels among strains isolated from patient B.The expression levels of as-partate protein genes(SAPP1,SAPP2,and SAPP3)in various strains isolated from patients A and B increased.The expression levels of SAPP1 and SAPP2 in strain G1 were higher than those in G2 and G3(both P＜0.05).There was no statistically significant difference in the expression levels of SAPP1,SAPP2,and SAPP3 genes in strains from patient B.Conclusion Clinical isolates of C.parapsilosis have higher biofilm formation and aspartate protease production abilities than standard strain.The expression of virulence factors varies among strains isolated from different specimens,while there is no significant difference in the expression of virulence factors among strains isolated at different periods.Patients may have been infected with different MT types of C.parapsilosis in multiple sites during the same period.