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.

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

Objective:To study the protective effect and effect of SphK1 overexpression on the injury of nerve cells induced by acrylamide.Methods:ACR with 99% purity was prepared into 1.25 mmol/L and 2.5 mmol/L solutions. SH-SY5Y cells were divided into control group (NC group) , experimental group and SphK1 activator group. The experimental group was given ACR solution with final concentration of 1.25 mmol/L and 2.5 mmol/L respectively for 24 h. In the SphK1 activator group, on the basis of the exposure concentration of the experimental group, the SphK1 specific activator (12-) phorbol tetradecanoate (-13-) acetate (PMA) solution[prepared by dimethyl sulfoxide (DMSO) , the final concentration was 100 nmol/l], and other treatments were the same as the experimental group. Control group (NC group) added PMA solution into normal cells. Western blot was used to detect the expression of SphK1 protein; CCK-8 was used to detect the proliferation of SH-SY5Y cells; hoechst33342 method was used to observe the morphological changes of nerve cells; flow cytometry was used to analyze the apoptosis of cells.Results:Compared with NC group, the expression of SphK1 protein in the experimental group and the SphK1 activator group was significantly lower ( P<0.05) . Compared with the experimental group, the expression of SphK1 protein in each concentration of SphK1 activator group was increased, and the difference was statistically significant ( P<0.05) . In addition to 1.25 mmol/L SphK1 activator group, compared with NC group, the relative growth survival rate of experimental group and 2.5 mmol/L SphK1 activator group were lower, the difference was statistically significant ( P<0.05) . Compared with the experimental group, the relative survival rate of cells in the SphK1 activator group was higher, and the difference was statistically significant ( P<0.05) . With the increase of exposure concentration, the cells in the experimental group showed the morphological characteristics of early apoptosis at ACR 1.25 mmol/L and late apoptosis at ACR 2.5 mmol/L. Compared with NC group, the apoptosis rate of experimental group and SphK1 activator group at ACR 2.5 mmol/L was significantly different ( P<0.05) ; compared with experimental group, the apoptosis rate of SphK1 activator group at ACR 2.5 mmol/L was lower, the difference was statistically significant ( P<0.05) . Conclusion:The SphK1 excessive expression plays the protective function to the nerve cell damage caused by acrylamide.

Objective:To study the protective effect and effect of SphK1 overexpression on the injury of nerve cells induced by acrylamide.Methods:ACR with 99% purity was prepared into 1.25 mmol/L and 2.5 mmol/L solutions. SH-SY5Y cells were divided into control group (NC group) , experimental group and SphK1 activator group. The experimental group was given ACR solution with final concentration of 1.25 mmol/L and 2.5 mmol/L respectively for 24 h. In the SphK1 activator group, on the basis of the exposure concentration of the experimental group, the SphK1 specific activator (12-) phorbol tetradecanoate (-13-) acetate (PMA) solution[prepared by dimethyl sulfoxide (DMSO) , the final concentration was 100 nmol/l], and other treatments were the same as the experimental group. Control group (NC group) added PMA solution into normal cells. Western blot was used to detect the expression of SphK1 protein; CCK-8 was used to detect the proliferation of SH-SY5Y cells; hoechst33342 method was used to observe the morphological changes of nerve cells; flow cytometry was used to analyze the apoptosis of cells.Results:Compared with NC group, the expression of SphK1 protein in the experimental group and the SphK1 activator group was significantly lower ( P<0.05) . Compared with the experimental group, the expression of SphK1 protein in each concentration of SphK1 activator group was increased, and the difference was statistically significant ( P<0.05) . In addition to 1.25 mmol/L SphK1 activator group, compared with NC group, the relative growth survival rate of experimental group and 2.5 mmol/L SphK1 activator group were lower, the difference was statistically significant ( P<0.05) . Compared with the experimental group, the relative survival rate of cells in the SphK1 activator group was higher, and the difference was statistically significant ( P<0.05) . With the increase of exposure concentration, the cells in the experimental group showed the morphological characteristics of early apoptosis at ACR 1.25 mmol/L and late apoptosis at ACR 2.5 mmol/L. Compared with NC group, the apoptosis rate of experimental group and SphK1 activator group at ACR 2.5 mmol/L was significantly different ( P<0.05) ; compared with experimental group, the apoptosis rate of SphK1 activator group at ACR 2.5 mmol/L was lower, the difference was statistically significant ( P<0.05) . Conclusion:The SphK1 excessive expression plays the protective function to the nerve cell damage caused by acrylamide.

Objective To estimate the value of team-based learning ( TBL ) in the teaching of occupational health and occupational medicine for foreign students. Methods 42 foreign students from the majorofclinicalmedicineinHarbin Medical UniversitywereselectedtoformtheTBLdiscussiongroup. Before class, teachers assigned tasks, and the students were taught with the same teachers with TBL teaching method. The effect of learning was evaluated by questionnaire and classroom test. The t test was performed using SPSS 19.0 statistical software for comparison of the results of individual test and group test. Results The result of the questionnaire showed that students agreed that TBL teaching can improve students' interest, self-study ability and broaden their learning ideas. The classroom test results showed that after the TBL discussion, the test scores of occupational oncology and pneumoconiosis were significantly higher than those of individual test. The difference was statistically significant (P<0.05). Conclusion The TBL method can significantly improve the students' comprehension of knowledge and enhance their learning effect.

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

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 investigate the therapeutic effect of free thinning anterolateral thigh flap for reconstruction of soft tissue defects after resection of buccal carcinoma.Methods From January 2012 to April 2015,15 cases with buccal carcinoma received radical resection and immediate reconstruction with free thinning anterolateral thigh flap.The flap size ranged from 8 cm × 6 cm to 12 cm × 8 cm.Results Flap necrosis happened in one case.The other 14 flaps survived completely with good color and texture.The patients were followed up for 6-36 months with good appearance and function.There was no malfunction on donor site.One case(T3N1M0) died 16 months after operation.1 case(T3N1M0) had local recurrence 8 month later.Conclusions The free thinning anterolateral thigh flap has reliable blood supply with minimal morbidity on donor sites.It is a good choice for reconstruction with good cosmetic and functional results.