Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To analyze the distribution characteristics and application value of liver,renal func-tion indexes and autoantibody-related indexes of neuromyelitis optica spectrum disorder(NMOSD).Methods The liver,renal function and autoantibody-related indexes data of patients diagnosed with NMOSD and multiple sclerosis(MS)in Beijing Tiantan Hospita,Capital Medical University from June 2015 to June 2023,as well as gender and age-matched controls underwent routine physical examination were retrospectively collected.A total of 95 patients with NMOSD(NMOSD group),230 patients with MS(MS group),and 244 healthy controls(routine physical examination group)were selected to evaluate the diagnostic value of each index for NMOSD.Results Compared with MS group,the levels of alanine aminotransferase,as well as the positive rates of α-hydroxybutyrate dehydrogenase,y-glutamyltransferase,anti-SS-A antibody,anti-SS-B anti-body,anti-ribosomal P protein antibody and Ro-52 antibody were significantly increased in NMOSD group,while the levels of albumin,indirect bilirubin and total bilirubin were significantly decreased,and the differ-ences were statistically significant(P＜0.05).The difference index between NMOSD and conventional physi-cal examination group was similar to that of MS group.The seven indexes,a-hydroxybutyrate dehydrogenase,albumin,globulin,direct bilirubin,indirect bilirubin,total bile acid and uric acid alkalinity could be used for the diagnosis of NMOSD.The area under the curve of combined diagnosis of NMOSD was 0.969,and the sensitiv-ity and specificity were 92.6％and 92.9％.Conclusion Multiple indexes of liver and kidney function in NMOSD patients are different from those in MS patients and healthy subjects underwent routine physical ex-amination,and the positive rate of some autoantibody indexes in NMOSD patients is higher than that in MS patients.Liver,renal function and autoantibody-related indexes can be used clinically to assist diagnosis,and the combined application of multiple indexes can further enhance its diagnostic value.

Objective:To establish and verify a diagnostic model for distinguishing multiple sclerosis (MS) from other neurological diseases with similar symptoms by usingcerebrospinal fluid oligoclonal band (CSF-OCB)combined with IgG intrathecal synthesis indicators and biochemical markers.Methods:Multiple sclerosis (MS) patients admitted to the Neurology Department of Beijing Tiantan Hospital affiliated with Capital Medical University from January 2014 to December 2022 were selected as the case group, while patients with similar neurological symptoms were selected as the control group. Using the case-control study design, a retrospective analysis was conducted on the detection of age, gender, oligoclonal bands in cerebrospinal fluid, IgG intrathecal synthesis indicators and biochemical indicators for all study subjects. The differential diagnosis model was determined by the multiple logistic regression analysis, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of the differential diagnosis model for neurological diseases with similar symptoms to MS and other conditions.Results:This study included 167 patients in the case group and 335 patients in the control group, of which 128 patients in the case group and 265 patients in the control group were used to construct the model, and 39 patients in the case group and 70 patients in the control group were used for model validation. The differential diagnostic model constructed by a multivariate logistic regression model was Y=0.871×CSF-OCB-0.051×CSFprotein-0.231×CSFchloride+1.183×gender-0.036×LDH+35.770. The model showed that the area under the curve, sensitivity and specificity were respectively 0.916, 87.3% and 87.6%. The Delong test results showed that the diagnostic efficacy of the model was significantly different from OCB, IgG intrathecal synthesis indicators, and OCB combined with IgG intrathecal synthesis indicators ( P<0.05). The new model validation showed that the actual diagnostic consistency rate for the MS group was 84.6%, while the actual diagnostic consistency rate for the control group was 90.0%. Conclusion:This study combines OCB, IgG intrathecal synthesis indicators, and biochemical indicators to establish a diagnostic prediction model for neurological diseases with similar clinical symptoms in MS. This model may have good differential diagnostic value and can better assist clinical diagnosis in the early stages of disease progression in MS patients.

This article reports a case data of primary malignant melanoma of the penis admitted to the Affiliated Hospital of Qinghai University. A 56-year-old patient was admitted to the hospital 1 month after the discovery of a penile mass. Physical examination: An irregular cauliflower-like mass about 1.5 cm×2.0 cm in size was seen below the external urethral orifice, covered with yellow necrotic tissue, and tenderness was positive. Several nodes were palpable in the left and right groin areas, tenderness positive. Laboratory examination showed no abnormality. The CT examination of head, chest, abdomen and pelvis showed no obvious abnormality. The biopsy of the penile mass showed malignant melanoma of the penis. The pathological results of biopsy of the right inguinal lymph node considered local inflammation. Combined with the patient's medical history, physical examination, imaging examination and lymph node biopsy results, a diagnosis of primary penile malignant melanoma was made. Partial penile resection was performed, and the postoperative pathological diagnosis was malignant melanin invasion of the epidermis with ulceration. There was no local recurrence and metastasis during the 9-month follow-up.

Objective To evaluate the performance of two molecular point-of-care testing(POCT)prod-ucts in the diagnosis of influenza A virus(Flu A)and influenza B virus(Flu B)of clinical samples,and pre-liminarily evaluate the clinical diagnostic value of the changes of infection-related indicators in peripheral blood.Methods A total of 491 oropharyngeal swabs from patients with influenza-like symptoms who were treated in the hospital were recruited into this study from November 1,2019 to June 30,2023.These swabs were collected using reverse transcription real-time quantitative fluorescent polymerase chain reaction(RT-qPCR),and two POCT molecular products,XpertTM Xpress Flu/RSV and EasyNAT? Flu Assay,respectively.The diagnostic performance of two POCT molecular products was analyzed using RT-qPCR reaction as a standard.According to the results of RT-qPCR method,the subjects were divided into Flu A positive group,Flu B positive group and negative group(both Flu A and Flu B were negative).The levels of indicators in pe-ripheral blood of the three groups were compared to evaluate the value of these indicators in the clinical diag-nosis of Flu A and Flu B.Results Among the 491 patient specimens,the XpertTM Xpress Flu/RSV assay showed the sensitivity for Flu A was 96.88%,and the specificity was 99.75%,and the sensitivity for Flu B was 100.00%,and the specificity was 100.00%.EasyNAT? Flu Assay assay showed the sensitivity for Flu A was 94.79%,and the specificity was 96.81%,and the sensitivity for Flu B was 100.00%,and the specificity was 100.00%.And two POCT molecular methods performed well consistency(Kappa value was 0.974).There was no significant difference in the levels of C-reactive protein and serum amyloid A among the negative group,Flu A positive group,and Flu B positive group(P>0.05).But the levels of white blood cell count in the negative group were higher than those in the Flu A positive group and Flu B positive group(P<0.01).Conclusion In this paper,two typical molecular POCT products are studied.Their sensitivity and specificity are highly consistent with the results of RT-qPCR.Molecular POCT products have the advantages of flexibil-ity and rapidity,which are of great value for the improvement of clinical diagnosis and treatment.Molecular detection combined with peripheral blood infection related indicators is helpful for the early diagnosis of influ-enza virus infectious diseases.

Objective To analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

Objective:To compare the characteristics of cerebrospinal fluid (CSF) oligoclonal band electrophoresis examination results between patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), and to provide a basis for the differential diagnosis of the two types of neurological demyelinating diseases.Methods:Case analysis.The retrospective study method was used, and the patients who visited Beijing Tiantan Hospital, Capital Medical University from January 2020 to August 2023 were selected as the research subjects, including 70 MS patients[19 males and 51 females, aged 34 (28, 44) years] and 70 GBS patients [44 males and 26 females, aged 50 (36, 61) years]. The oligoclonal band electrophoresis and immunoglobulin G(IgG) index (IgG I) were performed on the clinical specimens from MS and GBS patients, and CSF routine, CSF biochemistry (glucose, chloride, protein), lactate, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), rubella virus (RV), toxoplasma gondii (TOX), Epstein-Barr virus (EBV), and coxsackievirus were detected simultaneously. The enumeration data were treated with the chi-square test. The measurement data didn′t accord with normal distribution, and were treated with the Mann-Whitney U test. Results:The positive rate of oligoclonal band (OCB) electrophoresis in MS and GBS patients were 80.00% (56/70) and 4.29% (3/70), respectively. The positive rate in MS patients was significantly higher than that in GBS patients (χ 2=82.289, P<0.001). The white blood cells count [5.50 (3.00, 11.00)/μl] and the level of chlorine [127 (125, 128) mmol/L] in CSF of MS patients was higher than that of GBS patients [3.50(2.00, 7.00)/μl, 126(124, 128) mmol/L] ( U=-2.245, P<0.05; U=-2.028, P<0.05), while the levels of CSF protein [33.40(27.61, 39.17)mg/L], glucose [3.59(3.36, 3.88) mmol/L], and lactate [1.55(1.40, 1.73) mmol/L] of MS patients were lower than those of GBS patients [6.71(43.78, 138.30) mg/L, 3.97(3.55, 4.54) mmol/L, 1.80(1.60, 2.00) mmol/L]( U=-6.747, P<0.001; U=-3.651, P<0.001; U=-4.531, P<0.001). The levels of IL-6 [3.36(2.34, 5.02) pg/ml], IL-8 [55.40(46.75, 66.40) pg/ml], and TNF-α [5.63(4.25, 6.63) pg/ml] in CSF of MS patients were lower than those of GBS patients [6.12(3.61, 11.73) pg/ml, 120.00(74.90, 187.80) pg/ml, 6.57(5.25, 8.03) pg/ml]( U=-3.463, P<0.05; U=-5.225, P<0.001; U=-2.785, P<0.05). The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were 36.36% (24/66), 0 and 0, respectively,and the positive rates of those of GBS patients were 85.71% (54/63), 30.16% (19/63), and 19.05% (12/63), respectively. The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were significantly lower than those of GBS patients (χ 2=32.839, P<0.001; χ 2=23.343, P<0.001; χ 2=13.861, P<0.001). Conclusions:The MS patients mainly showed the higher positive rates of OCB. The GBS patients showed elevated CSF protein levels but no significant increase in white blood cell count, namely albuminocytologic dissociation in CSF. Meanwhile, the GBS patients showed elevated levels of intrathecal immunity and inflammation indicators, and a higher positive rate of pathogen antibodies.

ObjectiveTo evaluate the clinical effectiveness and safety of acupuncture with manipulation for lumbar disc herniation in remission period. MethodsOne hundred and four patients with lumbar disc herniation in remission were randomly divided into a treatment group and a control group， with 52 cases in each group. Treatment group applied acupuncture with manipulation of pointing， pulling， and shaking. Acupoints were selected as lumbar Jiaji （EX-B2， bilateral）， Ashi point， Shenshu （BL 23， bilateral）， Huantiao （GB 30， bilateral）， Weizhong （BL 40， opposite side of the affected area）， Chengshan （BL 57， opposite side of the affected area）. The control group applied lumbar traction plus acupoint ultrasonic pulse penetration therapy （acupoints selection same as the treatment group）； 20 minutes each time， 3 times a week， a total of 3 weeks for both groups. The primary outcome was the improvement rate of lumbar disc herniation symptoms and signs， which was calculated at 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up， respectively； the secondary outcome were the Japanese Orthopaedic Association （JOA） scores， Visual Analogue Scale （VAS） scores， and Oswestry Disability Index （ODI） scores （including ODI total scores， sitting scores and standing scores）， which were evaluated before treatment， 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up； clinical effectiveness was assessed at 3 months follow-up； and the occurrence of adverse events in the participants， as well as blood routine， urine routine， stool routine， and electrocardiograms before and after the treatment were recorded to evaluate safety. ResultsTwo patients from each group fell out， and 50 patients of each group were included in the outcome analysis ultimately. The scores of lumbar disc herniation symptoms and signs improved more in the treatment group than in the control group at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up （P＜0.01）. The JOA scores of participants in both groups at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up were higher than those before treatment in the same group， and the VAS scores， ODI total scores， ODI sitting scores and standing scores were significantly lower than those before treatment in the same group （P＜0.05）， and the JOA scores of patients in the treatment group were higher than those of the control group at all time points， and the VAS scores， ODI total scores， ODI sitting scores and standing score were lower than those of the control group （P＜0.05）. At the 3 months follow-up， the excellent rate of the treatment group was 70.00% （35/50） better than that of the control group， which was 50.00% （25/50） （P＜0.05）. There were no abnormalities in blood， urine， stool routines and electrocardiograms before and after treatment in both groups， and no adverse events occurred. ConclusionAcupuncture with manipulation of pointing， pulling， and shaking for treating patients with lumbar disc herniation in remission has a better safety on pain relief and improving quality of life， and the effectiveness is better than lumbar traction plus acupoint ultrasonic pulse penetration therapy.