OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.
Humans ; Middle Aged ; Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Biopsy ; Disease Progression

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective:To study the change of soil environment and yield of Angelica sinensis when cultivated on the film side and and open field sides，and to explore the influence of garlic volatiles and film-side cultivation on continuous cropping A. sinensis，so as to provide some certain theoretical basis for the saying that the A. sinensis garlic intercropping mode and film-side cultivation could alleviate continuous cropping A. sinensis. Method:In this study， the effects of garlic on soil environment and yield of A. sinensis cultivated on film side and crop rotation were discussed through the determination and analysis of soil microorganism quantity，soil enzyme activity and yield of Angelica sinensis in the rhizosphere of A. sinensis. Result:The number of bacteria and actinomycetes in the rhizosphere soil of A. sinensis increased significantly， while the number of fungi decreased significantly. Among them， the number of bacteria and actinomycetes in the intercropping of A. sinensis and garlic on the film side increased by 104% and 146.89% on average as compared with that of the control （monoculture under continuous cropping open field），and the number of fungi decreased by 39.28% on average as compared with that of control group. When the enzyme activity in the rhizosphere soil was significantly increased under the condition of intercropping with garlic on the film side，the soil urease，sucrase，alkaline phosphatase and acid phosphatase activities under the intercropping of A. sinensis and gralic on the rotation film side were increased by 61.60%，51.09%，203.48% and 76.19% respectively as compared with those in control group. The yield of A. sinensis significantly increased under the condition of intercropping with garlic on the film-side，and the yield of Angelica sinensis under the rotation film-side intercropping with garlic increased by 39.37% as compared with that of control group. Conclusion:Under the mode of film-side cultivation，the interplanting of A. sinensis with garlic can change the number of soil microorganism，improve the activity of soil enzyme，improve the physical and chemical properties of soil， alleviate the obstacle of continuous cropping and guarantee the healthy growth of A. sinensis more effectively.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective: This study aimed to evaluate the association between occupational radiation exposure and changes in thyroid hormone levels among medical radiation workers. Methods: This retrospective cohort study included 2,946 radiation workers from 20 Guangzhou hospitals. Data on general characteristics, participant radiation dosimetry, and thyroid function test results [thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroid hormone (T4)] were extracted from dosimetry and medical records. The generalized estimating equation was used to evaluate the trend of changes in thyroid hormone levels over time and was adjusted for age, gender, and occupation. Results: The average annual effective dose was very low and showed a general downward trend. During the follow-up period, changes in T3 and T4 levels among radiation workers were -0.015 [95% confidence interval ( Conclusion Thyroid hormone secretion might be affected even in low-dose radiation exposure environments.
Adult ; China ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure/adverse effects* ; Radiation Exposure/adverse effects* ; Retrospective Studies ; Thyroid Hormones/radiation effects* ; Young Adult

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

Objective:To explore the allelopathic effect of garlic volatiles on Angelica sinensis by studying the allelopathic effect of both living garlicand isolated garlic sprout volatiles on A. sinensis, and provide certain theoretical basis for Angelica garlic interplanting mode to alleviate the stress of continuous cropping A. sinensis. Method:Through the determination and analysis of the growth indexes and leaf protective enzyme system of A. sinensis，the adaptability of A. sinensis to continuous cropping stress and non-continuous cropping stress environment under the influence of the volatiles of living garlic and isolated garlic sprout as well as the mechanism of resistant growth and development were discussed. Result:The overall analysis showed that the growth index and leaf protective enzyme activity of isolated garlic sprout with alleloinductive treatment（DC2）under continuous cropping stress were increased by 17.51% and 48.34% respectively as compared with those under single cropping（CK1）. The growth index and leaf protective enzyme activity of angelica under continuous cropping and intercropping（LC2）were increased by 16.63% and 36.65% as compared with those under monocrop cropping（CK2）. Those indicated that the volatiles of isolated garlic sprout had more significant effect than those of live garlic on alleviating the stress of continuous cropping of A. sinensis. Conclusion:Regardless of the presence of continuous cropping obstacle，appropriate concentrations of living garlic and isolated garlic sprout volatiles had an allelopathic promoting effect on angelica root growth index and leaf protective enzyme activity，and the effect was more obvious in continuous cropping stress conditions，so intercropping garlic has a certain role in alleviating angelica's continuous cropping stress.