Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in the patients with acute cerebral infarction,and to analyze the correlation of TCM syndromes with collateral circulation,cerebral blood perfusion and prognosis.Methods A total of 300 patients with acute cerebral infarction were selected.All patients underwent head-neck CT angiography(CTA)and CT perfusion imaging(CTP),and then were followed up for 30 days.The prognosis was evaluated by modified Rankin Scale(MRS)score.In addition,the dynamic evolution of TCM syndromes was observed to explore the correlation of TCM syndromes with collateral circulation,cerebral blood flow perfusion in the lesion area and prognosis.Logistic regression analysis was used to explore the influences of TCM syndromes,blood flow perfusion and collateral circulation establishment on stroke outcomes.Results(1)Highest incidences of syndrome elements of phlegm,blood stasis and wind were presented in ACI patients.The syndrome element of qi deficiency was predominated in the patients with anterior/posterior communicating artery opening and extracranial-to-intracranial collateral circulation establishment.On the first day of onset,the incidence of qi deficiency syndrome element in the good collateral circulation group was lower than that in the poor collateral circulation group(P＜0.05).On the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good collateral circulation group were significantly lower than those in the poor collateral circulation group(P＜0.01).The results of correlation analysis showed that the score of qi deficiency was negatively correlated with regional cerebral blood volume(rCBV)of region of interest(r=-0.472,P＜0.05),and the score of yin deficiency was positively correlated with rCBV(r=-0.557,P＜0.01)on the first day of onset.The incidence of qi deficiency in the lesion area was relatively high in the patients of decreased rCBV(rCBV＜1.0 score)group(P＜0.01),while the incidence of yin deficiency in the lesion area was relatively high in the patients of elevated rCBV(rCBV＞1.0 score)group(P＜0.05).(2)The distribution of syndrome elements on the first day of onset showed that the incidence of qi deficiency syndrome element in the poor prognosis group was significantly higher than that in the good prognosis group(P＜0.01);on the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good prognosis group was significantly lower than those in the poor prognosis group(P＜0.05 or P＜0.01).The incidence of phlegm syndrome element in the good prognosis group was significantly reduced on the 30th day after onset compared with that on the first day of onset(χ2=7.409,P＜0.01),while there was no significant difference shown in the poor prognosis group(P＞0.05).(3)Logistic regression analysis showed that syndrome elements(qi deficiency,phlegm),collateral circulation grading,and rCBV in the lesion area were the independent risk factors for stroke outcomes.Conclusion The acute cerebral infarction patients with poor collateral circulation,decreased blood perfusion and poor prognosis are predominated by qi deficiency syndrome element.Moreover,phlegm syndrome element is presented in the patients with poor prognosis throughout the course of disease.It is indicated that qi deficiency syndrome element and phlegm syndrome element play an important role in the pathogenesis and progression of acute cerebral infarction.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To explore the clinical application value of single pass scanning using muti-slice spiral CT for polytrauma patients.Methods:Totally 60 polytrauma patients treated from January to November in 2023 were randomly enrolled in this study. They were categorized into an experimental group and a control group using a random number table, with 30 patients in each group. The patients in the experimental group underwent single pass scaning for the head, neck, chest, and abdomen, whereas those in the control group receiving separate scanning for various parts. Then, the noise, signal-to-noise ratio (SNR), and contrast-to-noise (CNR) of the CT images of both groups were recorded. Furthermore, the objective and subjective evaluation, volume CT dose index (CTDI vol), effective dose ( E), scanning time, and scan ranges of the images were compared between both groups. Results:Compared to the control group, the test group exhibited lower SNR of the head ( t = -5.47, P < 0.05) and higher SNR and CNR of the chest scans ( t = -5.95, -6.15, P < 0.05). Furthermore, the test group demonstrated decreased ED, CTDIvol, scanning time, and scan range, which dropped from 18.53 mSv to 13.81 mSv ( t = 3.29, P < 0.001), from 15.77 mGy to 10.59 mGy ( t = 4.48, P< 0.001), from 31.68 s to 10.97 s ( t = 6.95, P < 0.001), and from 64.92 cm to 45.21 cm ( t = 9.05, P < 0.001), respectively compared to the control group. Conclusions:Single pass CT scanning can reduce E, scanning time, and scan range in the treatment of polytrauma patients while ensuring the high quality of CT images, thus warranting wide clinical applications.