A novel series of 2-aryl substituted benzothiopyranone compounds was designed and synthesized based on our previously obtained benzothiopyranone scaffold with significant antituberculosis activity. All target compounds were evaluated for their antimycobacterial activity and preliminary druggability was subsequently investigated for some selected compounds with good activity. The results indicated that most compounds showed good activity against Mycobacterium tuberculosis H₃₇Rv. Among them, compounds 8g, 8h, 8q and 9f showed potent activity with MIC ranged from 0.2 to 0.4 μg·mL^-1. Furthermore, some active compounds exhibited low cytotoxicity and cardiotoxicity risk. It is worth noting that compounds 8h and 8q with good liver microsome stability and low inhibition of CYPs 3A4/5 and 2C9 were suitable for combination drug regimen to treat tuberculosis.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

With advancements in radiology,endoscopic techniques,surgical treatments,cell biology and molecular biology,the un-derstanding of temporomandibular disorders(TMD)has increased.The temporomandibular joint(TMJ)is a complex structure comprising both soft and hard tissues.Within the TMJ,the temporomandibular disc is a soft tissue structure that connects the mandible to the skull,providing cushioning and stability during joint movement.Different imaging techniques have their own advantages and limi-tations in the diagnosis and treatment of TMD.Therefore,using image registration technology to assess the condition and position of the articular disc provides new research perspectives for evaluating TMD,which may contribute to the diagnosis and treatment.This article reviews the latest advancements in TMJ imaging,explores the applications of various image registration techniques,particularly in the context of TMD diagnosis and treatment,and discusses future prospects.Combining the research results of some scholars at home and a-broad with the author’s clinical experience,the article aims to provide valuable insights for clinicians.

With the effects of activating blood and resolving stasis, and moving Qi to relieve pain, Jingtong Granules is widely used in the treatment of cervical radiculopathy in China. Long-term clinical application and related evidence have shown that the prescription has ideal effect in alleviating the pain in neck, shoulder, and upper limbs, stiffness or scurrying numbness, and scurrying pain caused by this disease. However, there is a lack of consensus on the clinical application of Jingtong Granules. Therefore, clinical first-line experts and methodology experts from all over the country were invited to compile this expert consensus. This expert consensus is expected to guide clinicians to use Jingtong Granules in a standardized and reasonable way, improve clinical efficacy, reduce medication risks, and benefit patients. First, according to the clinical experience of experts and the standard development procedures, the indications, syndrome characteristics, clinical advantages, and possible adverse reactions of Jingtong Granules were summarized. Then, through face-to-face interview of clinical doctors in traditional Chinese medicine and western medicine and survey of the clinical application, the clinical problems were summed up, and the consensus was reached with the nominal group method to form the final clinical problems. Third, evidence retrieval was carried out for the clinical problems, and relevant evidence was evaluated. The GRADE system was employed to rate the quality of evidence. Fourth, 5 recommendation items and 3 consensuses items were summarized with the nominal group method. Opinions and peer reviews on the consensus content were solicited through expert meetings and letter reviews. The final consensus includes the summary of evidence on the clinical indications, effectiveness, and safety of Jingtong Granules, which can serve as a reference for clinicians in hospitals and primary health institutions.
Humans ; Drugs, Chinese Herbal/adverse effects* ; Consensus ; Radiculopathy/drug therapy* ; Medicine, Chinese Traditional ; Pain/drug therapy*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.
Humans ; Sleep Initiation and Maintenance Disorders/therapy* ; Transcranial Magnetic Stimulation ; Brain-Derived Neurotrophic Factor ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; gamma-Aminobutyric Acid ; Depressive Disorder

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA. METHODS: Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs. RESULTS: The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs. CONCLUSION Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.
Humans ; Apoptosis ; Cartilage/metabolism* ; Chondrocytes/metabolism* ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 3/metabolism* ; MicroRNAs/metabolism*