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.

Objective To explore Professor Wu Liqun's medication law for treating tic disorders in children.Methods Medical records of tic disorders children treated by Professor Wu Liqun from September 2016 to October 2022 were collected,and a database was established.SPSS Statistics 23 was used for frequency statistics,and Liquorice software was used for multi-scale backbone network analysis and multi-layer core network analysis to summarize the medication law.Results Totally 709 medical records were included,involving 834 prescriptions and 203 kinds of Chinese materia medica.The drug categories were mostly tonic drugs,heat-clearing drugs,and liver-pacifying and wind-relieving drugs.The properties of the drugs were mainly warming,cold,and mild,and the meridians were mostly in the lung,liver,and spleen meridians.Complex network analysis showed that the core prescription consisted of 20 kinds of Chinese materia medica,such as Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Codonopsis Radix,and 30 groups of commonly used medicine pairs and commonly used medicines with different symptoms and commodities were obtained.Conclusion Professor Wu Liqun's treatment for tic disorders in children focuses on treating"liver wind",evacuating external wind to cut off the course of the disease,soothing the liver and subduing yang to extinguish internal wind,paying attention to regulating liver qi,nourishing yin and soothing the liver,nourishing blood and extinguishing wind.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Pelagic cephalopods have evolved a series of fascinating traits,such as excellent visual acuity,high-speed agility,and photophores for adaptation to open pelagic oceans.However,the genetic mechanisms underpinning these traits are not well understood.Thus,in this study,we obtained high-quality genomes of two purpleback flying squid species(Sthenoteuthis oualaniensis and Sthenoteuthis sp.),with sizes of 5450 Mb and 5651 Mb,respectively.Comparative genomic analyses revealed that the S-crystallin subfamily SL20-1 associated with visual acuity in the purple-back flying squid lineage was significantly expanded,and the evolution of high-speed agility for the species was accompanied by significant positive selection pressure on genes related to energy meta-bolism.These molecular signals might have contributed to the evolution of their adaptative preda-tory and anti-predatory traits.In addition,the transcriptomic analysis provided clear indications of the evolution of the photophores of purpleback flying squids,especially the recruitment of new genes and energy metabolism-related genes which may have played key functional roles in the pro-cess.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.

Objective To analyze the risk factors of failure of internal fixation of unstable femoral intertrochanteric fractures treated with proximal femoral nail anti-rotation (PFNA) in elderly patients,and to provide reference for clinical treatment.Methods Collected the clinical data of 251 aged and unstable femoral intertrochanteric fracture patients who have recieved PFNA treatment from January 2012 to December 2016.Preoperative clinical general data and intraoperative clinical factors were used as analysis variable to analyze the high risk factors and risk factors of internal fixation failure in PFNA treatment by χ2 test ,Wilcoxon rank sum test and Logistic regression.Results Through the analysis of 78 aged patients with internal fixation failure after PFNA treatment,the χ2 test and Wilcoxon rank sum test showed that,type of fractures,osteoporosis Singh index grade, tip-apex distance,application of hormone,basic diseases were risk factors for internal fixation failure after PFNA treatment (P<0.05).Among thses factors,type of fractures,osteoporosis Singh index grade, tip-apex distance were independent high risk factors for internal fixation failure after PFNA treatment(P<0.05).Conclusion Severe type of fractures (type Ⅲ and Ⅳ),osteoporosis of grade 4 to 6,and tip-apex distance greater than 25 mm are high risk factors of failure of internal fixation of unstable femoral intertrochanteric fractures treated with PFNA,and it is better to give more attention and effective intervention or other treatment.

Objective To evaluate atrial septal defect (ASD) occlusion employing a small right anterior thoracotomy approach. Methods A total of 21 patients with ASD underwent general anesthesia and 2 -3 cm incision was made in the fourth right intercostal space. Utilizing transesophageal or transthoracic echocardiography, the occluder was released using a monotube unit. Results All patients were occluded successfully. No patient required open surgery utilizing extracorporeal circulation. There were no major complications and no evidence of residual atrial shunt. Conclusion ASD occlusion via a minimal surgical incision is safe, less invasive, and has excellent outcomes.

To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.

OBJECTIVETo screen the point mutation of the low-density lipoprotein receptor (LDL-R) gene in Chinese familial hypercholesterolemia (FH) patients, characterize the relationship between the genotype and the phenotype and discuss the molecular pathological mechanism of FH.

METHODSA patient with clinical phenotype of homozygous FH and her parents were investigated for mutations in the promoter and all eighteen exons of the LDL-R gene. Screening was carried out using Touch-down PCR and direct DNA sequencing; multiple alignment analysis by DNASIS 2.5 was used to find base alteration, and the LDL-R gene mutation database was searched to identify the alteration. In addition, the apolipoprotein B gene (apo B) was screened for known mutations (R3500Q) that cause familial defective apo B100 (FDB) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTSTwo new heterozygous mutations in exons 4 and 9 of the LDL-R gene were identified in the proband (C122Y and T383I) as well as her parents. Both of the mutations have not been published in the LDL-R gene mutation database. No mutation of apo B100 (R3500Q) was observed.

CONCLUSIONTwo new mutations (C112Y and T383I) were found in the LDL-R gene, which may result in FH and may be particularly pathogenetic genotypes in Chinese people.

Adult ; Apolipoproteins B ; genetics ; Asian Continental Ancestry Group ; Child ; China ; Female ; Heterozygote ; Homozygote ; Humans ; Hyperlipoproteinemia Type II ; genetics ; Male ; Mutation ; Receptors, LDL ; genetics