Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560) Conclusions Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

Objective:To improve the analytical method of radionuclide 14C, and estimate the internal dose caused by 14C to human, in order to protect the health of workers and the public in workplaces involving potential 14C exposure. Methods:Urine samples were pretreated by wet oxidation. In the analysis, potassium persulfate was used as an oxidant to decompose urea into carbon dioxide, which was absorbed by 1 mol/L sodium hydroxide, and the absorption solution was converted into calcium carbonate precipitation. After calcium carbonate powder was prepared into sample source by suspension method, the low background liquid scintillation counter was applied to measure the radioactivity, which can be used for calculating the result.Results:The reaction time optimized by using carbamide as carrier was 1 h. For 80 ml urine, the amount of potassium persulfate used was 10 g. The method recovery rate reached about 100%. Four real urine samples were tested using the optimized method, and the result of activity concentration 14C was 0.32, 0.60, 0.86 and 0.74 Bq/L, respectively. Conclusions:The optimized method had good stability, high accuracy and stable experimental result, which could meet the needs of routine radiological detection. The establishment of a quantitative method for 14C in urine sample has improved the methodological system for 14C monitoring.

Objective To explore the diagnostic value of MR elastography and diffusion?weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty?four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference(F=61.690, P<0.01). The ADC values in three groups were (1.31 ± 0.14)×10-3, (1.23 ± 0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference(F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05),(9.56±0.57),(17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non?invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role.

Objective To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.Methods The data of 45 cases with cervical posterior longitudinal ligament ossification treated by ACAF from March 2017 to October 2017 were retrospectively analyzed,including 25 males and 20 females,age 45-68 years,average 57.5 years.There were 18 cases involving C3 vertebral body,30 cases involving C4 vertebral body,40 cases involving C5 vertebral body,34 cases involving C6 vertebral body,and 7 cases involving C7 vertebral body.The function of the neural function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system at preoperation and latest follow-up.The curvature of the cervical spine was measured on the lateral X-ray film of the cervical spine,the maximum occupying ratio of the spinal canal was measured on the cross section of the CT scan,and compression of the cervical spinal cord was evaluated by the cervical MRI.Results Patients were followed up for 3 to 6 months (average,3.9 months).The improvement of neurological function was obtained in all the patients.The JOA score improvement rate at the latest follow-up was 71.3％±9.6％.The cervical lordosis was improved from preoperative 4.5°±3.8° to 10.3°±4.8° at the latest follow-up.The canal stenosis ratio was decreased from preoperative 54.3％±8.2％ to 12.5％±5.3％ at the latest follow-up.MRI showed that the cervical spinal cord was adequately decompressed in situ.No specific complications were identified that were associated with this technique.Conclusion The present study elaborates the surgical tips and demonstrates the satisfactory outcome of ACAF for the treatment of OPLL.This novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis. However, there is increasing evidence in the literature for secondary SUNCT being attributable to certain known lesions. We explored the possible neurobiological mechanism underlying SUNCT based on all reported cases of secondary SUNCT for which detailed information is available. Here we report a case of neuromyelitis optica spectrum disorders that had typical symptoms of SUNCT that might have been attributable to involvement of the spinal nucleus of the trigeminal nerve. We also review cases of secondary SUNCT reported in the English-language literature and analyze them for demographic characteristics, clinical features, response to treatment, and imaging findings. The literature review shows that secondary SUNCT can derive from a neoplasm, vascular disease, trauma, infection, inflammation, or congenital malformation. The pons with involvement of the trigeminal root entry zone was the most commonly affected region for inducing secondary SUNCT. In conclusion, the neurobiology of secondary SUNCT includes structures such as the nucleus and the trigeminal nerve with its branches, suggesting that some cases of primary SUNCT have underlying mechanisms that are related to existing focal damage that cannot be visualized.
Headache Disorders ; Headache* ; Inflammation ; Neurobiology ; Neuromyelitis Optica ; Pons ; Tears* ; Trigeminal Nerve ; Vascular Neoplasms

Objective: To study the protective effect of Ascorbic acid (AA) on the injury of nickel-exposed mouse embryonic fibroblasts (NIH/3T3) . Methods: A model of damage induced by 50 μg/mL nickel refining dust was established to determine the relative survival rate of cells, superoxide dismutase (SOD) , lactate dehydrogenase (LDH) and glutathione peroxidase. (GSH-Px) activity, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) content, and p53 (wild-type) , Bcl-2 protein expression. To investigate the protective effect of different doses of ascorbic acid (25, 50, 100 mmol/L) on nickel-refined dust-induced NIH/3T3 cell injury. Results: The study showed that ascorbic acid Ⅲ group can make the NIH/3T3 cell survival rate increased significantly; Apoptosis rate was reduced; The vitality of SOD and GSH-Px increased significantly, and the difference was statistically significant (P<0.05) . At the same time, the level of MDA and H₂O₂ and the activity of extracellular LDH enzyme were significantly reduced, and the difference was statistically significant (P<0.05) . The results showed that nickel refining dust induced cell damage through up-regulation of p53 protein and down-regulation of Bcl-2 protein expression; ascorbic acid interventions, the expression level of Bcl-2 protein in ascorbic acid II and III groups was higher than that of nickel refining dust group, and the difference was statistically significant (P<0.05); The expression level of p53 protein in each dose group of ascorbic acid was lower than that of nickel refined dust group, and the difference was statistically significant (P<0.05). Conclusion With the increase of concentration of ascorbic acid, oxidative damage levels, antioxidant enzyme levels, reduce cell apoptosis, reduce expression of p53, increased expression of Bcl-2. It showed that ascorbic acid had protective effect on NIH/3T3 cell injury induced by nickel refining dust.

Objective To obsevre the peptidyl-prolyi isomerase 1 (PIN1) and Nanog expreesions in glioma tissues and the effect of PIN1 inhibitor polyiso-butylene (PiB) on their expressions and U87 cell proliferation.Methods Eighty-four glioma samples (15 with WHO graded Ⅱ,27 with WHO graded Ⅲ and 42 with WHO graded Ⅳ),collected in our hospital from March 2013 to August 2014,were chosen in our study; their expressions of PIN1 and Nanog were detected by immunohistochemical staining; U87 glioblastoma cell lines were cultured; 0.2,0.5,1.0 and 2.0 μg/mL PiB was given to the cells for 24 and 48 h,and then,MTT assay was employed to detect the inhibited effect and inhibition ratio was calculated; 1.0 μmol/L PiB group (U87 cells treated with 1.0 μmol/L PiB for 24 h) and control group (U87 cells without any treatment) were chosen,immunofluorescence staining was used to detect the PIN1 and Nanog protein expressions,and real time-PCR and Western blotting were employed to observe the mRNA and protein expressions of PIN1 and Nanog.Results The positive protein expression rate of PIN1 and Nanog in gliomas of different grades (WHO graded Ⅱ,Ⅲ and Ⅳ) was significantly different (P＜0.05):the higher the malignancy grade,the higher the rate of positive protein expression of PIN1 and Nanog.MTT assay indicated that PiB could inhibit the cell proliferation in dose-and concentration-dependent manners; as compared with the control group,1.0 μmol/L PiB group had significantly decreased percentages of PIN1+,Nanog+ and PIN1+/Nanog+ cells (P＜0.05); the mRNA PIN1 expression quantity in the control group and 1.0 μmol/L PiB group was 1.82±0.03 and 0.94±0.20,and that of Nanog was 1.47±0.04 and 0.82±0.19,with significant differences (P＜0.05); the protein PIN1 expression quantity in the control group and 1.0 μmol/L PiB group was 2.96±0.05 and 1.15±0.26,and that of Nanog was 1.52±0.16 and 0.75±0.05,with significant differences (P＜0.05).Conclusion PIN1 and Nanog play important roles in the pathogenesis of human gliomas and are related to the glioma malignancy; PIN1 may participate in the regulation of Nanog,and there is a pathway between the two genes; the glioma cell proliferation ability is suppressed by down-regulating the PIN1-Nanog expression.