To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

Objective To analyze the effects of probiotics combined with montmorillonite powder on intestinal mucosa and expressions of intestinal microorganism function-related genes in neonatal rats with rotavirus(RV)infection.Methods RV infection model was established by intragastric administration of SA11 strain rotavirus.Forty-eight suckling rats were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),experimental group(0.06 g·mL-1 montmorillonite powder)and combined group(0.06 g·mL-1 montmorillonite powder+6.5 × 107 CFU·mL-1 Saccharomyces cerevisiae powder)with 12 rats in each group.The feces were collected for evaluation.The levels of serum tumor necrosis factor-a(TNF-a),interleukin-1 β(IL-1 β)and IL-17 were detected by enzyme-linked immunosorbent assay,the levels of aquaporin(AQP)in intestinal tissues was detected by real-time fluorescence quantitative polymerase chain reaction,and the counts of Bifidobacteria and Escherichia coli in feces were detected by bacterial 16srDNA fluorescence quantitative polymerase chain reaction.Results The feces scores in normal,model,experimental and combined groups were(1.01±0.10),(2.97±0.08),(2.84±0.03)and(2.77±0.03)points;TNF-α levels were(132.54±14.63),(185.66±19.64),(165.25±17.63)and(149.95±15.76)pg·mL-1;IL-1β levels were(172.32±18.68),(265.34±27.72),(202.34±21.34)and(186.24±19.46)pg·mL-1;IL-17 levels were(118.62±12.44),(173.24±18.25),(152.32±16.72)and(122.54±13.58)pg·mL-1;Bifidobacteria counts were(6.35±0.64),(4.31±0.44),(4.93±0.50)and(5.34±0.54)CFU·g-1;Escherichia coli counts were(6.14±0.62),(8.78±0.88),(8.46±0.85)and(8.12±0.83)CFU·g-1;mRNA levels of AQP2 were 1.02±0.05,0.72±0.07,0.89±0.08 and 1.21±0.12;mRNA expression levels of AQP4 were 1.04±0.07,0.42±0.05,0.78±0.08 and 1.19±0.12;mRNA expression levels ofAQP8 were 1.00±0.06,0.63±0.06,0.91±0.09 and 1.30±0.13,respectively.There were significant differences of above indexes between the model group with the normal,experimental and combined groups(all P＜0.05).Conclusion Montmorillonite powder combined with probiotics can improve fecal properties,reduce serum inflammatory factors and correct intestinal flora disorders in neonatal rats with RV infection,which may be related to improving the expressions of intestinal A QP2,AQP4 and AQP8.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndrome types in diabetic kidney disease(DKD),and to explore the correlation between TCM syndrome types and laboratory indices,so as to provide an objective basis for the TCM syndrome differentiation and treatment of DKD.Methods Syndrome differentiation was carried out in the 157 patients with DKD at stages Ⅲ and Ⅳ,and then the distribution of the syndromes of deficiency in the origin and the syndromes of excess in the superficiality was explored.The levels of 24-hour urinary total protein(24hUTP),serum creatinine(Scr),blood urea nitrogen(UREA),plasma albumin(Alb),total cholesterol(TC),and triglyceride(TG)of the patients were detected,and then the relationship between the TCM syndrome types and the biochemical indexes was analyzed.Results(1)The distribution of the syndromes of deficiency in the origin in DKD patients at different stages showed that DKD patients at stage Ⅲ were mainly differentiated as yin deficiency and dryness-heat syndrome[58.57％(41/70)],qi and yin deficiency syndrome[28.57％(20/70)],yin and yang deficiency syndrome[10.00％(7/70)],and spleen and kidney qi deficiency syndrome[2.86％(2/70)];DKD patients at stage Ⅳ were mainly differentiated as yin deficiency and dryness-heat syndrome[40.23％(35/87)],qi and yin deficiency syndrome[29.89％(29/87)],spleen and kidney qi deficiency syndrome[18.39％(16/87)],and yin and yang deficiency syndrome[11.49％(10/87)].The differences in the distribution of the syndromes of deficiency in the origin among the DKD patients at different stages were statistically significant(P<0.05).However,with the progression of the disease,DKD patients at different stages in general showed a trend of the decrease in the proportion of yin deficiency and dryness-heat syndrome while the increase in the proportions of qi and yin deficiency syndrome,spleen and kidney qi deficiency syndrome,and yin and yang deficiency syndrome.(2)The distribution of the syndromes of excess in the superficiality in DKD patients at different stages showed that DKD patients at stage Ⅲ were mainly differentiated as damp-heat syndrome[54.29％(38/70)],phlegm-stasis syndrome[27.14％(19/70)],blood-stasis syndrome[10.00％(7/70)],and cold-damp syndrome[8.57％(6/70)];DKD patients at stage Ⅳ were mainly differentiated as damp-heat syndrome[44.83％(39/87)],phlegm-stasis syndrome[35.63％(31/87)],cold-damp syndrome[14.94％(13/87)],and blood-stasis syndrome[4.60％(4/87)].There were no significant differences in the distribution of the syndromes of excess in the superficiality among the DKD patients at different stages(P>0.05).(3)The analysis of relationship between TCM syndrome type and biochemical indexes showed that Scr and UREA levels of DKD patients with spleen and kidney qi deficiency syndrome were significantly higher than those of patients with yin deficiency and dryness-heat syndrome,and the differences were statistically significant(P<0.05);Scr and 24hUTP levels of DKD patients with cold-damp syndrome were significantly higher than those of patients with damp-heat syndrome,and the differences were statistically significant(P<0.05).Conclusion DKD patients at stages Ⅲ and Ⅳ are all predominantly suffering from yin deficiency and dryness-heat syndrome,and with the progression of the disease,the syndrome of yin deficiency and dryness-heat develops into qi and yin deficiency syndrome,spleen and kidney qi deficiency syndrome,and yin and yang deficiency syndrome sequentially.Pathogenic dampness and blood stasis are the main pathogenic factors of DKD.And Scr,UREA,and 24hUTP are correlated with the TCM syndrome types of DKD,which will be helpful for the differentiation of TCM syndrome types of DKD.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective To analyze the registered clinical trials of headache treated by TCM;To discuss the current research status;To provide reference for the optimization of subsequent clinical trial research plans.Methods All clinical trials of headache treated by TCM were retrieved from the ChiCTR and the ClinicalTrials.The retrieval time was from the database establishment to May 22,2023.The general characteristics,study types,intervention measures and outcome indicators of the trials were analyzed respectively.Results A total of 104 registered studies were included,with the number of registered studies increasing since 2004 and reaching a peak in 2020,involving 25 provincial administrative regions or countries and 69 clinical trial institutions;the funding sources were mainly scientific research funds of universities,national finance and local finance.The research type was mainly intervention research;the designing scheme was mainly randomized parallel control study;the high frequency random method was simple random method;45 registered studies used blind methods.Exploratory studies/pre-trials were the most commonly used in the phases of clinical researches.Most of the registered studies were single-center clinical trials with a total sample size of 9 648 patients.The main interventions were acupuncture and oral Chinese medicines.The high frequency outcome indicators included life quality of score,headache attack frequency,headache attack days and headache severity,etc.There were some problems in outcome indicators,such as non-standard,lack of TCM characteristic advantages,and insufficient patient participation.Conclusion The number of registered studies of headache treated by TCM has increased by year,but there are some problems in design elements,such as random method,blind method,number of research centers,sample size and the setting of outcome indicator.

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.