Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal

OBJECTIVE: To investigate the predictive value of circulating free DNA (cfDNA) combined with interleukin 10 (IL-10) in predicting central nervous system infiltration (CNSI) in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 63 patients with DLBCL in our hospital from May 2021 to April 2023 were retrospectively analyzed. The 63 patients were divided into CNSI group (15 cases) and non-CNSI group (48 cases) base on whether CNSI occurred. The age, sex, Ann Arbor stage, ECOG score, IPI risk, CNS-IPI risk, number of extranodal sites involved, bone marrow involvement, hypertrophic disease, B symptoms, source cells, glucose quantification, Pandy test, cerebrospinal fluid (CSF) chlorine, CSF nucleated cell count, CSF protein, peripheral blood cfDNA, and IL-10 status were compared between the two groups. The correlation between cfDNA, IL-10 in peripheral blood and CSF protein was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of peripheral blood cfDNA and IL-10 on secondary CNSI in DLBCL patients. The last follow-up was on November 30, 2023. Kaplan-Meier method was used to calculate the time of secondary CNSI in the non-CNSI group. RESULTS: The IPI risk, CNS-IPI risk, number of extranodal sites involved, and CSF protein in the CNSI group were significantly higher than those in the non-CNSI group (all P <0.05). The levels of cfDNA and IL-10 in peripheral blood of CNSI group were significantly higher than those of non-CNSI group (both P <0.01). cfDNA and IL-10 in peripheral blood were both positively correlated with CSF protein (r =0.402 4, 0.315 1). ROC curve analysis showed that peripheral blood cfDNA and IL-10 had certain predictive value for CNSI, and the area under the curve (AUC) was 0.829 and 0.742, respectively. The AUC of the combined detection was 0.910, with a sensitivity of 80.00% and a specificity of 93.70%. The diagnostic efficacy was significantly higher than that of the two prediction values alone. The median follow-up time was 20 (6-31) months. Non-CNSI patients were grouped based on peripheral blood cfDNA combined with IL-10 positive or negative pairs. The time of secondary CNSI in positive group was significantly shorter than that in negative group (P <0.05). CONCLUSION cfDNA and IL-10 in peripheral blood of DLBCL patients with CNSI are significantly increased, and the combined detection of cfDNA and IL-10 has good predictive value for CNSI.
Humans ; Interleukin-10/blood* ; Lymphoma, Large B-Cell, Diffuse/blood* ; Retrospective Studies ; Female ; Male ; Cell-Free Nucleic Acids/blood* ; Middle Aged ; ROC Curve ; Prognosis ; Central Nervous System Neoplasms ; Central Nervous System/pathology* ; Adult ; Predictive Value of Tests

Objective To evaluate the therapeutic effect of evodiamine(Evo)on atopic dermatitis(AD)in rat models by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response ele-ment binding protein(CREB)signaling pathway.Methods A rat model of AD was established by administration of multiple doses of 2,4-dinitrochlorobenzene(DNCB).The animals were randomly divided into AD group,Evo-low-dose(Evo-L,5 mg/kg)group,Evo-high-dose(Evo-H,10 mg/kg)group,Evo-H+H-89(5 mg/kg)group and dexamethasone(0.1 mg/kg)group.Normal rats were used as the control group and then the degree of skin damage of rats in each group was scored.Abdominal blood was taken to detect the levels of interleukin-4(IL-4),cAMP,and tumor necrosis factor-α(TNF-α)in serum;Skin lesion tissue was collected to detect pathological change,counting of mast cells,PKA/CREB related protein expression and expression of IL-4 and TNF-α mRNA in the tissue.Results Compared with control group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions of AD group were reduced,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells and mRNA expression of IL-4 and TNF-α in skin lesion tissues were all significantly increased(P＜0.05).Compared with AD group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-L group,Evo-H group,and dexamethasone group were increased,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues all reduced(P＜0.05).Compared with the Evo-H group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-H+H-89 group was reduced and the severity score of skin lesion,level of IL-4 and TNF-α,epidermal thickness,num-ber of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues significantly increased(P＜0.05).Conclusions Evo inhibits inflammatory response and pathological damage through regulation of cAMP/PKA/CREB signaling pathway in AD rat models.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Objective:To analyze drug resistance, virulence and molecular epidemiological characteristics of Staphylococcus aureus ( S. aureus) isolated from skin sites of suppurative infections, and to provide an experimental basis for clinical anti-infective therapies. Methods:Swab samples from suppurative skin lesions and nasal secretions were collected from inpatients in Department of Dermatology, the Affiliated Hospital of Inner Mongolia Medical University from May 2020 to December 2020, and subjected to bacterial isolation and culture. Suspected S. aureus colonies were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Drug sensitivity test was conducted by using the broth microdilution method. Virulence genes of S. aureus were amplified by PCR, and real-time fluorescence-based quantitative PCR was performed to determine the relative expression of 4 virulence genes including tsst-1, pvl, hla and clfA in S. aureus strains from different sources. S. aureus strains were genotyped by multilocus sequence typing. Drug resistance rates and detection rates of virulence genes were compared by using chi-square test or Fisher′s exact test, and measurement data among groups were compared by using t test or Mann-Whitney U test. Results:A total of 85 strains of S. aureus were isolated from 210 inpatients, including 54 isolates from skin sites of suppurative infections (case group) and 31 isolates from the nasal cavity (control group) . Drug sensitivity test showed that 14 strains of methicillin-resistant S. aureus (MRSA) were identified among 85 strains of S. aureus. The resistance rate to penicillin was the highest (90.59%, 77/85) in the 85 S. aureus strains; the resistance rates to clindamycin and erythromycin were 60.00% (51/85) and 61.18% (52/85) respectively; no strains showed resistance to rifampicin, vancomycin or linezolid. PCR showed that the detection rate of the pvl gene was 33.33% (18/54) in the case group, which was significantly higher than that in the control group (12.90%, 4/31; χ2= 4.28, P= 0.038) . Real-time fluorescence-based quantitative PCR showed that the relative expression level of the clfA gene was significantly higher in the control group (3.87[2.30, 5.94]) than in the case group (1.63[0.95, 2.62], P= 0.007) . A total of 17 ST types were identified among the 85 strains of S. aureus, and the dominant types were ST398-methicillin-susceptible S. aureus (20/71) and ST22-MRSA (9/14) . The detection rate of the virulence gene pvl was significantly higher in the ST22-MRSA strain (14/14) than in the non-ST22 MRSA strains (0, P < 0.001) . Conclusions:S. aureus strains isolated from the skin sites of suppurative infections were highly resistant to penicillin, clindamycin and erythromycin, so these antibiotics should not be used as the first-choice empiric treatment. The occurrence of cutaneous S. aureus infections may be associated with the virulence gene pvl, and the nasal colonization of S. aureus may be associated with the clfA gene.

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.
Angelica sinensis/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Plant Roots/chemistry* ; China

Angelicae Sinensis Radix， derived from a medicinal and edible plant Angelica sinensis， is one of the traditional bulk Chinese medicines. In addition to gynecological blood stagnation and deficiency， its indications also include dysmenorrhea， deficiency and cold-induced abdominal pain， and rheumatoid arthritis. With the in-depth study of Angelicae Sinensis Radix， its anti-inflammatory and analgesic activities have attracted widespread attention. However， there has been no systemic report. The present study comprehensively reviewed the anti-inflammatory and analgesic activities of Angelicae Sinensis Radix （including its compositions， extracts， and different processed products） and mechanisms published in recent 30 years. The anti-inflammatory effect of Angelicae Sinensis Radix was achieved mainly by blocking the expression of proteins and genes in nuclear factor-κB （NF-κB）， mitogen-activated protein kinases （MAPK）， and Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathways， inhibiting the release of inflammatory mediators including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， nitric oxide （NO）， prostaglandin E₂ （PGE₂） and IL-1β， and maintaining the high sensitivity of immune cells in the host to external stimuli. The mechanism of analgesic effect may be related to the suppression of the production of algesic substances （such as inflammatory factors and chemokines） or blocking of the amplification and transmission of pain perception in cascade reaction. Furthermore， the study also pointed out some problems in modern research and proposed suggestions on its future research to provide references for investigation and clinical applications of Angelicae Sinensis Radix.

Objective:To investigate the genetic correlation of interleukin-12 (IL-12) pathway-related gene single nucleotide polymorphisms (SNPs) with psoriasis vulgaris and their interaction with HLA-Cw*0602 in populations of Mongolian and Han nationalities in Inner Mongolia.Methods:From December 2012 to March 2018, 1 409 inpatients with psoriasis vulgaris (1 030 of Han nationality and 379 of Mongo-lian nationality) and 1 483 healthy controls (965 of Han nationality and 518 of Mongolian nationality) were collected from the Affiliated Hospital of Inner Mongolia Medical University, and served as patient group and control group respectively. Five milliliters of peripheral venous blood samples were collected from these subjects, and DNA was extracted. Nine SNPs located in the coding regions of IL-12 pathway-related genes were selected, including IL-12B (rs2082412, rs2288831, rs3212227, rs3213094, rs7709212) , IL-23R (rs11209026, rs2201841, rs7530511) and IL-28RA (rs4649203) genes, and detected by next-generation sequencing. HLA-Cw*0602 was genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) . Statistical analysis was carried out with PLINK1.07 software, Chi-square test was used to compare allele frequencies between the 2 groups, relative risk estimates of alleles were calculated by using odds ratio ( OR) , and chi-square test for R × C contingency tables was used for haplotype analysis. Results:The allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in the patients with psoriasis vulgaris of Han nationality than in the controls of Han nationality (all P < 0.005) ; the allele frequency of rs3213094 in the IL-12B gene was significantly lower in the patients of Mongolian nationality than in the controls of Mongolian nationality ( P < 0.005) . The prevalence of HLA-Cw*0602 was significantly lower in the patients with psoriasis vulgaris of Han and Mongolian nationalities than in the controls of corresponding nationalities (both P < 0.005) . As stratification analysis showed, the allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in HLA-Cw*0602-positive patients of Han nationality than in HLA-Cw*0602-positive controls of Han nationality (all P < 0.005) , while there was no significant difference between HLA-Cw*0602-negative patients of Han nationality and HLA-Cw*0602-negative controls of Han nationality (all P > 0.05) . Among the HLA-Cw*0602-positive or negative populations of Mongolian nationality, no significant difference was observed in the allele frequencies between the patients and controls (all P > 0.005) . Haplotypes were constructed using 5 SNPs in the IL-12B gene, and there was no significant difference in the frequencies of 6 haplotypes between the patients and controls of Mongolian or Han nationality (all P > 0.005) ; stratification analysis showed that there was no significant difference in the frequencies of 7 haplotypes between HLA-Cw*0602-positive/negative patients and controls of Mongolian or Han nationality (all P > 0.005) . Conclusion:IL-12 pathway-related gene polymorphisms are associated with psoriasis vulgaris in the populations of Mongolian and Han nationalities in Inner Mongolia, and there may be interaction between IL-12B and HLA-Cw*0602 in the occurrence of psoriasis vulgaris.

Objective:To investigate the relationship of polymorphisms in metabolic syndrome-related genes with psoriasis vulgaris (PsV) and their interaction with HLA-C*06:02 in populations of Mongolian nationality.Methods:Totally, 379 PsV inpatients of Mongolian nationality and 518 healthy controls of Mongolian nationality were collected from the Affiliated Hospital of Inner Mongolia Medical University from December 2012 to March 2018. Sixteen previously reported single nucleotide polymorphisms (SNPs) and HLA-C*06:02, which were related to metabolic syndrome and its components, were selected. Next-generation sequencing and polymerase chain reaction-sequence specific primer (PCR-SSP) typing were performed to determine the genotypes of these subjects. Minor allele frequencies of the 16 mutation sites and HLA-C*06:02 were calculated in the PsV group and control group, and chi-square test was used to analyze the differences in the minor allele frequencies of SNPs between the 2 groups.Results:There was no significant difference in the minor allele frequencies of the 16 SNPs susceptible to metabolic syndrome between the Mongolian PsV patients and healthy controls (all P > 0.05), while the minor allele frequency of HLA-C*06:02 significantly differed between the 2 groups ( P = 4.09 × 10 -35, OR = 3.41). Among the HLA-C*06:02-positive subjects, the minor allele frequencies of rs7593730_T and rs6931514_G significantly differed between the 252 PsV patients and 191 healthy controls ( P = 0.016, OR = 0.64; P = 0.041, OR = 1.33, respectively) ; no significant difference was observed in the minor allele frequencies of the 16 SNPs between the PsV patients and healthy controls among the HLA-C*06:02-negative subjects ( P > 0.05) . Conclusion:The SNPs of rs7593730 and rs6931514 may be related to PsV in populations of Mongolian nationality in Inner Mongolia, and may interact with HLA-C*06:02.