Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

OBJECTIVE: To explore the serological characteristics and bioinformatics analysis results of 4 blood donors with RHCE*cE(281C, 282T) variant allele. METHODS: A total of 4 non-related blood donors with RHCE*cE (281C, 282T) variant allele (donors 1-4) were selected as the study objects. They donated blood at Shenzhen Blood Center from January 2022 to June 2023. The 4 blood donors were all Han. And 5 mL elbow venous blood was collected from these 4 blood donors. Regular serological assaying with 4 kinds of monoclonal antibody reagents was used for determination of the RhCcEe type. The nucleotide sequences of all 10 exons and adjacent flanking intron regions of RHCE gene in these 4 donors were analyzed by Sanger sequencing, and the full-length haplotype analysis of RHCE gene was performed by using the single-molecule real-time sequencing (SMRT) third-generation technology. DeepTMHMM software was used to analyze the structure of protein transmembrane region of wild type and variant RhCcEe protein and predict the location of amino acid substitution. The effects of mutations on RhCcEe protein function were analyzed using PolyPhen-2, SIFT and Mutation Taster bioinformatics software. Robetta and Swiss-PdbViewer v4.1.0 were used for modeling the tertiary structures of RhCcEe to analyze the difference between wild type and variant RhCcEe protein. The mutation was rated according to the standards and guidelines for the classification of genetic variants of the American College of Medical Genetics and Genomics (ACMG). This study has been approved by the Medical Ethics Committee of Shenzhen Blood Center (Approval No. SZBCMEC-2022-024). RESULTS: The RhCcEe phenotypes of the 4 blood donors were CCEweake by serological assaying. The RhE antigen were weakly expressed form 0 to 3+. The analysis of RHCE gene sequence indicated that all the 4 donors with RHCE*cE (281C, 282T) allele. The mutation caused the substitution of a single amino acid in the RhCcEe protein (p.Leu94 Pro) and the amino acid substitution was located in the transmembrane α3 chain resulted in significant changes in the 3D structure of the extracellular region of RhCcEe protein. The substitution was predicted to be "Probably damaging", "Damaging" and "Polymorphism" by PolyPhen-2, SIFT and Mutation Taster bioinformatics software. According to the guidelines of ACMG, the variant was rated to be likely pathogenic. CONCLUSION The RHCE*cE (281C, 282T) variant allele was first found in the Han Chinese population. The serological data of this allele were enriched. It provides an important guarantee for the safety of blood transfusion. Bioinformatics analysis provided evidences for further study of the structure and functions of RhCcEe protein.
Humans ; Blood Donors ; Computational Biology/methods* ; Alleles ; Rh-Hr Blood-Group System/genetics* ; Male ; Female ; Adult ; Exons

Objective To study the medication law of TCM compounds for ischemic stroke using data mining methods;To provide reference for clinical medication.Methods Literature about TCM treatment for ischemic stroke was retrieved from CNKI,VIP,Wanfang Data and SinoMed from May 31,2014 to May 31,2024.Drug frequency analysis,dosage analysis,property and taste attribution analysis,association rule analysis,factor analysis and clustering analysis were performed using Excel 2019,SPSS Modeler 18,SPSS 25 software.Results A total of 180 prescriptions for the treatment of ischemic stroke were included,involving 208 kinds of Chinese materia medica,with a total frequency of 1 996 times,of which 20 were high-frequency medicines(≥24 times),with Chuanxiaong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix,Paeoniae Radix Rubra and Carthami Flos being the most frequent;the efficacy of the medicines included activating blood circulation and removing blood stasis,tonifying the deficiency,pacifying the liver,calming the wind and clearing away heat;the main properties were warm,cold and neutral;the main tastes were bitter,sweet and pungent;the main meridians were liver,spleen,heart and lung meridians;among the drug dosages of drugs with frequency≥24,the mean dosage of Chuanxiong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix and Paeoniae Radix Rubra were 12.24,12.91,10.52,40.00,12.13 g,respectively.In the systematic clustering and complex network analysis,it was suggested that the core TCM prescriptions were:Xuefu Zhuyu Decoction with modified Banxia Baizhu Tianma Decoction,modified Chaihu Shugan Powder,Buyang Huanwu Decoction with modified Huangqi Guizhi Wuwu Decoction and modified Liujunzi Decoction.Conclusion TCM treatment for ischemic stroke mostly uses the methods of activating blood circulation and expelling phlegm,nourishing blood to promote blood circulation,clearing heat and cooling blood,and benefiting qi and neutralizing qi,which provides ideas and methods for following research.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: To study the genetic polymorphism of red blood cell blood group among in Shenzhen Han, Indian and Xinjiang Uyghur populations, to provide scientific basis for the demand prediction and collection strategy of rare blood group, and to explore the genetic differences of blood group between Han and Caucasians. METHODS: The haplotypes of antigen coding genes of 10 target blood group systems from 87 Han Chinese and 50 Indian blood donors in Shenzhen, and 49 healthy Uyghur people in Xinjiang were obtained by three-generation sequencing technology, and the polymorphism and frequency characteristics were analyzed. RESULTS: Only a single genotype was detected the Langereis and Vel blood group systems in samples from three different populations. Only one genotype of Dombrock blood group was detected in Shenzhen Han, and Junior blood group in Xinjiang Uygur populations. In the MNS, Duffy, Kidd, Dombrock and Junior blood group systems, the haplotype frequency of Indian and Uyghur people was significantly different from that of Han people. Compared with the Han ethnic group, the rare blood group s-, Fy(a-), Jk(a-b-), and Do(a+b-) have a higher frequency among the Uyghur and Indian populations. CONCLUSION Haplotype frequencies of antigen genes for MNS, Duffy, Kidd, Dombrock and Junior blood group system in Shenzhen Han, Indian and Uyghur populations displayed a polymorphic difference with unique distribution characteristics different from the ethnic groups in other regions.
Humans ; Blood Group Antigens/genetics* ; China/ethnology* ; Erythrocytes ; Ethnicity/genetics* ; Gene Frequency ; Genotype ; Haplotypes ; India/ethnology* ; Polymorphism, Genetic ; White People/genetics* ; Central Asian People/genetics* ; East Asian People/genetics*

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

OBJECTIVE: To observe the clinical effect of Fu's subcutaneous needling based on anatomy train theory for nonspecific low back pain (NLBP). METHODS: A total of 120 patients with NLBP were randomized into an anatomy train Fu's subcutaneous needling group (40 cases, 3 cases dropped out), a conventional acupuncture group (40 cases, 2 cases dropped out) and a conventional Fu's subcutaneous needling group (40 cases, 2 cases dropped out). Acupuncture was applied at ashi points and bilateral Shenshu (BL23) and Dachangshu (BL25) in the conventional acupuncture group, once every other day, 3 times a week. Fu's subcutaneous needling was applied at lumbodorsal myofascial trigger points (MTrPs) in the Fu's subcutaneous needling group, once every 3 days, twice a week. On the basis of the treatment in the Fu's subcutaneous needling group, Fu's subcutaneous needling was applied at MTrPs along the posterior superficial line and lateral line in the anatomy train Fu's subcutaneous needling group, once every 3 days, twice a week. All groups were treated for 2 weeks. Before and after treatment, the scores of numeric rating scale (NRS) and Oswestry disability index (ODI) were observed, the distance of Schober test was measured and the endurance of trunk extensors was assessed in the 3 groups. RESULTS: After treatment, in the 3 groups, the NRS and ODI scores were decreased compared with those before treatment (P<0.05), the Schober test distance was increased compared with that before treatment (P<0.05), the static and dynamic muscle endurance was increased compared with that before treatment (P<0.05). After treatment, in the anatomy train Fu's subcutaneous needling group, the NRS and ODI scores were lower than those in the conventional acupuncture group and the conventional Fu's subcutaneous needling group (P<0.05), the Schober test distance was longer than that in the conventional acupuncture group and the conventional Fu's subcutaneous needling group (P<0.05), the static and dynamic muscle endurance was superior to that in the conventional acupuncture group and the conventional Fu's subcutaneous needling group (P<0.05). CONCLUSION Fu's subcutaneous needling based on anatomy train theory can effectively relieve the pain symptom, enhance quality of life, improve lumbar motion and lumbar muscle function in patients with NLBP.
Humans ; Low Back Pain/physiopathology* ; Female ; Male ; Adult ; Acupuncture Therapy/methods* ; Middle Aged ; Acupuncture Points ; Young Adult ; Treatment Outcome ; Aged