ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

ObjectiveTo evaluate the effectiveness and safety of Sufei Pingchuan Formula （肃肺平喘方） in the treatment of bronchiectasis with airflow limitation， phlegm-heat obstructing the lung， and lung-spleen qi deficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 72 patients with stable bronchiectasis with airflow limitation of phlegm-heat obstructing the lung and lung-spleen qi deficiency syndrome were randomly divided into treatment group and control group， with 36 cases in each group. On the basis of regular inhalation of tiotropium bromide inhalation spray， the treatment group was given Sufei Pingchuan Formula granules， and the control group was given Sufei Pingchuan Formula granule simulant. The course of treatment in both groups was 12 weeks. The pulmonary function of both groups before and after treatment was observed， specifically focusing on forced expiratory volume in one second （FEV1）； the modified British Medical Research Council （mMRC） dyspnea scale， 24-hour sputum volume， COPD assessment test （CAT）， and traditional Chinese medicine （TCM） syndrome scores were assessed before treatment and after 4， 8， and 12 weeks of treatment； acute exacerbations were recorded at weeks 4， 8， and 12； additionally， changes in routine blood tests， urinalysis， liver and kidney function， and adverse events were monitored before and after treatment. ResultsAfter treatment， 4 patients in the treatment group and 6 in the control group dropped out. After 12 weeks of treatment， FEV1 increased in both groups compared to pre-treatment levels （P＜0.05）， but the difference between groups was not statistically significant （P＞0.05）. Compared to before treatment， the treatment group showed a reduction in mMRC scores after 12 weeks （P＜0.05） and a decrease in 24-hour sputum volume， CAT scores， and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）. In the control group， 24-hour sputum volume decreased after 12 weeks （P＜0.05）， and TCM syndrome scores decreased at weeks 8 and 12 （P＜0.05）. Compared to the control group， the treatment group showed a greater reduction in mMRC scores at week 12 （P＜0.05）， a decrease in 24-hour sputum volume and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）， and lower CAT scores at weeks 8 and 12 （P＜0.05）. The frequency and number of acute exacerbations in the treatment group were significantly lower than those in the control group at week 12 （P＜0.05）. No severe adverse events occurred in either group. ConclusionSufei Pingchuan Formula can improve the pulmonary function FEV1， the severity of dyspnea， reduce 24-hour sputum volume and frequent acute exacerbations， and improve the quality of life in patients with bronchiectasis and airflow limitation， with good safety.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Objective:To investigate the clinical characteristics, prognosis, and risk factors associated with disease progression within 24 months (POD24) after diagnosis in patients with splenic marginal zone lymphoma (SMZL) .Methods:Clinical data from 88 newly diagnosed SMZL patients treated at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between December 2009 and October 2022, were retrospectively analyzed. Patients were grouped based on the presence of POD24 for prognostic evaluation and comparison of clinical features.Results:There were 45 males (51.1% ) and 43 females (48.9% ), with a median age of 59 (24-82) years at the time of diagnosis. Ten (11.4% ) cases occurred POD24. The overall survival (OS) time and progression- free survival (PFS) time in the POD24 group were shorten than non-POD24 group [median OS time: 77 (11-159) months vs not reached, P<0.001; 15 (4-24) months vs 121 (24-154) months, P<0.001]. Univariate Cox analysis showed that Eastern Cooperative Oncology Group (ECOG) score ≥ 2 [ HR=8.942 (95% CI 1.097-72.910), P=0.041], age-adjusted International Prognostic Index (aaIPI) score of high-risk [ HR=5.070 (95% CI 1.256-20.461), P=0.023], POD24 [ HR=14.049 (95% CI 3.339-59.107), P<0.001], occurrence of tissue transformation [ HR=7.819 (95% CI 1.952-31.316), P=0.004], and disease unremission status after initial treatment [ HR=6.080 (95% CI 1.439-25.690), P=0.014] were the influencing factors for OS in SMZL patients. Multivariate analysis showed that POD24 [ HR=5.859 (95% CI 1.249–27.475), P=0.025] and occurrence of tissue transformation [ HR=5.520 (95% CI 1.050-29.009), P=0.044] were independent prognostic factors affecting OS. Univariate logistic analysis showed that ECOG ≥ 2 [ HR=7.556 (95% CI 1.498-38.110), P=0.014], high risk of aaIPI score [ HR=5.500 (95% CI 1.378- 21.945), P=0.016], occurrence of tissue transformation [ HR=8.000 (95% CI 1.759-36.383), P=0.007], and disease unremission status after initial treatment [ HR=9.136 (95% CI 2.216-37.675), P=0.002] were the influencing factors of POD24. Multifactorial analysis showed that disease unremission after initial treatment [ HR=8.253 (95% CI 1.681- 40.518), P=0.009] was an independent risk factor affecting POD24. Conclusions:POD24 and tissue transformation are independent poor prognostic factors for OS in SMZL patients. Patients with POD24 are at a higher risk of developing tissue transformation. The failure to alleviate the disease after initial treatment is an independent risk factor affecting POD24 patients.

Plasmablastic lymphoma (PBL) is a rare, highly aggressive non-Hodgkin lymphoma subtype for which no standardized therapeutic regimen has been established in clinical practice. This study retrospectively analyzed 18 PBL cases at Shanghai Ruijin Hospital from July 2012 to June 2024. Participants comprised 12 males and 6 females, with a median age of 59 (39–77) years. Twelve (66.7% ) cases presented at stage Ⅲ/Ⅳ, nine (50% ) have cytopenia, 12 (66.7% ) have increased lactate dehydrogenase level, and four (22.2% ) had a Ki-67 index of ≥90%. The tumor cells highly expressed CD38 (15/17, 88.2% ) /CD138 (12/17, 70.6% ), whereas the B-cell marker CD20 was rarely detected (1/17, 5.9% ). Of the 11 cases that underwent genetic sequencing, common mutations included TP53 (27.3% ), KMT2D (18.2% ), and TET2 (18.2% ). After excluding one patient with positive HIV who died without treatment, 17 patients received first-line therapy, achieving a complete response in 10 (58.8% ) and a partial response in 5 (29.4% ) cases. With the median follow-up time of 4.33 (0.17–12.17) years, Kaplan-Meier analysis indicated that the 2-year progression-free survival rate and overall survival rate were (68.5±11.2) % and (75.5±10.1) %, respectively.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is one of the most serious kinds of sperm defects, leading to asthenoteratozoospermia and male infertility. In this study, we use whole-exome sequencing to identify genetic factors that account for male infertility in a patient born from a consanguineous Pakistani couple. A homozygous frameshift mutation (c.1399_1402del; p.Gln468ArgfsTer2) in axonemal dynein light chain domain containing 1 ( AXDND1 ) was identified in the patient. Sanger sequencing data showed that the mutation was cosegregated recessively with male infertility in this family. Papanicolaou staining and scanning electron microscopy analysis of the sperm revealed severely abnormal flagellar morphology in the patient. Immunofluorescence and western blot showed undetectable AXDND1 expression in the sperm of the patient. Transmission electron microscopy analysis showed disorganized sperm axonemal structure in the patient, particularly missing the central pair of microtubules. Immunofluorescence staining showed the absence of sperm-associated antigen 6 (SPAG6) and dynein axonemal light intermediate chain 1 (DNALI1) signals in the sperm flagella of the patient. These findings indicate that AXDND1 is essential for the organization of flagellar axoneme and provide direct evidence that AXDND1 is a MMAF gene in humans, thus expanding the phenotypic spectrum of AXDND1 frameshift mutations.
Humans ; Male ; Sperm Tail/ultrastructure* ; Frameshift Mutation ; Infertility, Male/pathology* ; Pakistan ; Pedigree ; Consanguinity ; Axonemal Dyneins/genetics* ; Adult ; Spermatozoa ; Exome Sequencing