Objective:To analyze the effects of highdose methotrexate(HD-MTX)and lenalidomide as central nervous system(CNS)prophylaxis strategies in patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively.The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies.Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement.The CNS relapse-free survival(CRFS)rate,adverse effects,and the effects of different prophylaxis strategies on overall survival(OS)rate and progression-free survival(PFS)rate were evaluated in different groups and subgroups.Results:There were 200 patients enrolled in this study,80 cases in lenalidomide group and 120 cases in HD-MTX group.According to the delivery timing of prophylactic HD-MTX,the patients in HD-MTX group were further divided into two groups:80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval.At a median follow-up of 48(14-133)months,the 4-year CRFS rate,4-year PFS rate,and 4-year OS rate of the HD-MTX group was 93.6％,57.2％,and 68.8％,respectively,while that of the lenalidomide group was 90.4％,69.4％and 75.6％.There were no significant differences in 4-year CRFS rate,4-year PFS rate,and 4-year OS rate between HD-MTX group and lenalidomide group(all P＞0.05),but lenalidomide group showed a trend of improvement in PFS.Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups(91.7％vs 83.4％,P＞0.05),while 4-year PFS rate showed difference(49.5％vs 64.2％,P＜0.05).A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group,and 25 cycles occurred neutropenia accompanied with infection(10.1％),while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection(8.3％).Both the two groups had no treatment-related deaths.Conclusion:Compared with HD-MTX,lenalidomide combined with immunochemotherapy can prevent CNS relapse,at the same time,improve prognosis,which is a safe and well tolerated central prophylaxis strategy.

Objective:To investigate the characteristics of thalassemia gene types in children in Liuzhou,Guangxi.Methods:A total of 822 children suspected thalassemia aged from 1 day to 14 years who were admitted to our hospital from January 2019 to April 2022 were collected.Gap-PCR and PCR combined with reverse dot blot hybridization were used to detect α-and β-thalassemia genes.Results:Among 822 children,561 thalassemia carriers were detected,with a detection rate of 68.25％.Among them,303 cases were detected with α-thalassemia,and the most common genotype was--SEA/αα(163 cases),followed by-α3.7/αα(37 cases)and αcsα/αα(26 cases),44 cases with HbH disease.240 cases were detected with β-thalassemia,with a detection rate of 29.20％,and the most common genotype was βCD41-42/β N(112 cases),followed by βCD17/βN(75 cases)and βIVS-Ⅱ-654/β N(11 cases),11 cases with moderate to severe β-thalassemia.18 cases were detected with α β-thalassemia,with a detection rate of 2.19％,and--SEA/αα complex βCD41-42/βN was the most common genotype(4 cases).In Zhuang and Han populations,the detection ratio of-α3.7α/αα in α-thalassemia was the same(both 12.50％).While,the other main types such as--SEA/αα,αCSα/αα and-α4.2α/αα had certain differences.In β-thalassemia,CD41-42 and CD17 were the main genotypes detected in Han and Zhuang.Conclusion:In Liuzhou of Guangxi autonomous region,α-thalassemia is the main type in children,with a detection rate of 68.25％,and--SEA/αα is the most common genotype in mild thalassemia,followed by βCD41-42/βN.The detection rate of moderate to severe α-and β-thalassemia is relatively high.There are certain differences in the distribution of thalassemia among different ethnic groups.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective:To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods:Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results:A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes ( blaNDM-1, blaNDM-5, etc.) and virulence genes ( acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion:Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.

Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.

Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg-1·d-1 benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg-1·d-1 Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8th week of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8th week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels of CYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P＜0.01,P＜0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid and glycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.

Objective To investigate the effects of inhibition of chemokine C-X-C motif receptor 7(CXCR7)expression on the proliferation,migration,differentiation and mitochondrial function of human urine-derived stem cells(USCs)under hypoxia.Methods CXCR7 expression was inhibited by siCXCR7 and detected by Real-time PCR and Western blotting in hypoxia group treated with 3％O2 for 48 hours.Cell proliferation was detected by clonal formation assay and cell growth curve.Cell migration ability was detected by scratch assay and Transwell assay.Alkaline phosphatase,alizarin red,oil red O and alcian blue staining were used to detect the multidirectional differentiation ability of cells.Mitochondrial function was evaluated by JC-1 fluorescent probe,adenosine triphosphate(ATP)and reactive oxygen species(ROS).Results Compared with the normal oxygen group,the expression of CXCR7 in USCs in hypoxia group was significantly up-regulated,and hypoxia promoted the proliferation,migration and clonogenesis of USCs.SiCXCR7 inhibited the expression of CXCR7 and inhibited the effects of hypoxia on the proliferation,migration and clonogenesis of USCs,but had no effect on cell differentiation.Hypoxia treatment increased mitochondrial membrane potential and ATP levels,and decreased the production of reactive oxygen species,while CXCR7 inhibition decreased mitochondrial membrane potential and ATP production.Conclusion Hypoxia may enhance mitochondrial function of USCs through the CXCR7 signaling pathway,thereby promoting cell proliferation and migration.

Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.
Humans ; Asian People ; China/epidemiology* ; Ethnicity ; Genotype ; Gerbillinae ; Hepatitis B virus/genetics* ; Hepatitis B/virology*

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System