OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Immunotherapy had completely changed the treatment for patients with advanced non-small cell lung cancer.However,due to its low response rate as a monotherapy,many patients had not been able to benefit from the treatment.The combination of immunotherapy with anti-angiogenic drugs and chemotherapy might have helped to address this issue,and the regimen of atezolizumab with bevacizumab,carboplatin,and paclitaxel(ABCP)had been approved as a first-line treatment for advanced metastatic non-small cell lung cancer,holding great potential for application.This review had summarized the antitumor mechanisms of the ABCP regimen,had concluded the current status of its clinical application for different subgroups and treatment sequences,the safety and cost-effectiveness of the regimen,as well as the possibilities for alternative drug choices within the ABCP regimen and the development of new drugs,providing a reference for the personalized application of the ABCP regimen in patients with non-small cell lung cancer.

As global average carbon dioxide concentrations steadily rise,the frequency,intensity,and duration of cyanobacterial blooms in aquatic ecosystems are increasing annually.This phenomenon presents a significant threat to the overall health of global ecosystems and has garnered worldwide attention.In this study,an online detection of small-molecule dissolved gas concentrations in lake using a home-made membrane inlet mass spectrometer was conducted.Comparative water samples analyses demonstrated that the developed mass spectrometer instrument effectively discriminated between different water samples based on its dissolved gas detection capabilities.Online survey revealed that the concentrations of dissolved O2 and dissolved CO2 were 0.24 mmol/L and 1.31 μmol/L,respectively,in areas without cyanobacterial coverage.In areas with cyanobacterial coverage,their concentrations were 0.21 mmol/L and 0.92 μmol/L,respectively.In areas where cyanobacteria were densely collected,the dissolved CO2 content rose rapidly,while the dissolved O2 content decreased rapidly.This result revealed that large-scale cyanobacterial blooms exacerbated CO2 emissions,and during such blooms,lakes acted as sources of CO2,emitting substantial amounts into the atmosphere,thereby contributing to adverse impacts on global climate change.Furthermore,extensive cyanobacterial blooms led to a rapid decrease in dissolved O2 levels,resulting in O2 depletion and the mortality of fish and benthic invertebrates.The research highlighted the significance of the ratio of content of O2 and CO2 as a crucial indicator for cyanobacterial monitoring,with a smaller ratio indicating higher cyanobacterial content.Moreover,changes in turbidity and variations in the ratio of O2 and CO2 exhibited strong consistency.Large-scale algal blooms increased water turbidity,which posed a threat to the survival of aquatic organisms.This study provided a technological means for online detection of dissolved gases in water,offering essential references for water quality assessment,ecological evaluation,and particularly,for early prevention,mid-term management,and post-treatment effectiveness assessment of cyanobacterial blooms.

Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Objective To investigate the effect of Yaobitong Capsules combined with Fu's subcutaneous needling on lumbar range of motion and surface electromyography of trunk extensors in patients with lumbar disc herniation(LDH).Methods A total of 80 patients with LDH of blood stasis type were randomly divided into the study group and the control group,with 40 cases in each group.The control group was treated with Yaobitong Capsules orally,and the study group was given Fu's subcutaneous needling combined with Yaobitong Capsules orally.The course of treatment for the two groups covered 2 weeks.The changes of lumbar range of motion,pain visual analogue scale(VAS)score,improved Chinese Oswestry Disability Index(ODI)score,Roland-Morris Disability Questionnaire(RMDQ)score and surface electromyography of trunk extensors in the two groups before and after treatment were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 2 weeks of treatment,the total effective rate of the study group was 97.50%(39/40),and that of the control group was 80.00%(32/40).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the study group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the range of motion of lumbar flexion,extension and rotation in the two groups was significantly improved compared with that before treatment(P＜0.05),and the improvement of lumbar range of motion in the study group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the lumbar function scores of ODI score and RMDQ score in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of ODI score and RMDQ score in the study group was significantly superior to that in the control group(P＜0.01).(4)The pain VAS scores of the study group after one week,2 weeks and one month of treatment and the pain VAS scores of the control group after 2 weeks and one month of treatment were significantly lower than those before treatment(P＜0.05),and the decrease of pain VAS scores of the study group after one week,2 weeks and one month of treatment was significantly superior to that of the control group(P＜0.01).(5)After treatment,the parameters of surface electromyography of trunk extensors such as integrated electromyographic value(IEMG)and mean power frequency(MPF)in the two groups were obviously increased compared with those before treatment(P＜0.05),and the increase of MPF and IEMG in the study group was significantly superior to that of the control group(P＜0.01).Conclusion Yaobitong Capsules combined with Fu's subcutaneous needling can significantly enhance the curative effect of LDH patients,alleviate the lumbar range of motion,improve the surface electromyography of trunk extensors,and relieve muscle fatigue and pain symptoms.

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Osteoporosis and knee osteoarthritis often co-occur and are closely related in terms of epidemiology， clinical symptoms， pathogenesis and other aspects. Therefore， it is necessary to manage the co-morbidity and treat the two as a whole. Based on the overall relationship between wei （痿） and bi （痹） in TCM， it is believed that osteoporosis and knee osteoarthritis have marrow loss and bone atrophy as the core pathogenesis of co-morbidity， and microfractures as the central pathological link. The overall treatment is rooted in boosting kidney， supplementing marrow and strengthening the bones. According to the pathological manifestations of microfractures in the process of co-morbidity， and the different deficiency and excess characteristics of wei and bi， it can be divided into three types， "wei emerging with mild bi"， "wei and bi progressing simultaneously"， and "emphasis on both wei and bi"， for treatment. In terms of "wei emerging with mild bi"， that is the early stage of osteoporosis， the traditional Daoyin （导引） is the main therapy. For "wei and bi progressing simultaneously"， it can be divided into three stages further， including the onset stage， remission stage， and recovery stage of knee pain， treated with Taohong Siwu Decoction （桃红四物汤）， Bushen Huoxue Formula （补肾活血方） and self-made Bushen Qianggu Formula （补肾强骨方） as the main formula respectively. For "emphasis on both wei and bi"， the proven formula， Qianggu Zhitong Formula （强骨止痛方）， is taken as the main prescription.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.