1.Expert consensus on precise intervention with repetitive transcranial magnetic stimulation for sleep disorders in the elderly
Yuan SHAO ; Jian WANG ; Wei LIANG ; Yingli ZHANG ; Gangqiang HOU ; Xia LI ; Yi XING ; Lu WANG ; Shi TANG ; Yongjun WANG
Sichuan Mental Health 2026;39(2):97-105
In recent years, repetitive transcranial magnetic stimulation (rTMS) has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However, the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap, the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework, systematically screened randomized controlled trials (RCTs) and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly, highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization, thereby providing precise rTMS intervention protocol for sleep disorders in the elderly, aiming to enhance clinical efficacy while ensuring treatment safety. [Funded by National Key Research and Development Program (number, 2023YFC3603200); General Program of Shenzhen Science and Technology Innovation Commission (number, JCYJ20240813112859008, JCYJ20240813112900002); Youth Program of Shenzhen Kangning Hospital (number, KN2023A004); www.guidelines-registry.cn number, PREPARE-2026CN530]
2.The effect of body mass index and inferior pulmonary ligament division on the residual lung expansion after right upper lobectomy: A retrospective cohort study in a single center
Guang MU ; Wenhao ZHANG ; Hongchang WANG ; Yan GU ; Chenghao FU ; Wentao XUE ; Shiyuan XIE ; Tong WANG ; Ke WEI ; Yang XIA ; Liang CHEN ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):261-266
Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2<BMI≤23 kg/m2), a group B (23 kg/m2<BMI≤29 kg/m2) and a group C (BMI>29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.
3.Influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines and analysis of factors associated with poor prognosis in elderly patients with ischemic stroke
Hai LIANG ; Hong ZHANG ; Runan XIA ; Huijuan CHEN ; Mengyu JIANG ; Fanqin LI ; Panpan DI ; Miao YANG
China Pharmacy 2026;37(6):782-787
OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke, and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025, wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment, patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data, metabolic phenotype, the levels of platelet function indicators and inflammatory cytokines. Variables with P <0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included; among them, 162 cases were normal metabolic phenotype, 218 were intermediate metabolic phenotype, and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment, platelet aggregation rate, the levels of P-selectin and platelet activated complex-1 (PAC-1), high-sensitivity C-reactive Protein (hs-CRP), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the normal metabolic phenotype group, intermediate metabolic phenotype group, and poor metabolic phenotype group (except for platelet aggregation rate, and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group) were significantly lower than those before treatment in the same group. Moreover, the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time, and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time ( P <0.05). Univariate and multivariate Logistic regression analyses showed that combined with hypertension, combined with diabetes mellitus, and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke ( P <0.05). Multiple linear regression analysis showed that serum levels of hs-CRP, IL-1β, IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype ( P <0.05), with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype; CYP2C19 gene polymorphism, and in combination with hypertension and diabetes, can be used as independent predictors of poor prognosis.
4.Study on the construction of a red blood cell rare blood type database and physical repository in the Guangzhou Region
Zhijian LIAO ; Shuangshuang JIA ; Yuan SHAO ; Boquan HUANG ; Chunyan MO ; Jizhi WEN ; Runqing ZHANG ; Xia RONG ; Hong LUO ; Huaqin LIANG ; Yanli JI
Chinese Journal of Blood Transfusion 2026;39(5):619-628
Objective: To conduct screening for rare blood types within important blood group systems for the Chinese population, such as Rh, Duffy, Kidd, P1Pk, Diego, and MNS, in the Guangzhou region, and to establish a corresponding rare blood type database and physical repository. Methods: The saline medium microplate method was used to screen blood donors with the ccDEE phenotype combined with either Jk(a-) or Jk(b-). The polybrene microplate method was employed to screen for donors with Fy(a-), s(-), Lu(b-), Di(b-), k(-), and p phenotypes. The urea lysis microplate method was applied to screen for the Jk(a-b-) phenotype. A high-resolution melting (HRM) curve method was established for screening some donors with the Di(b-) phenotype. Subsequently, expanded phenotyping of antigens in the Rh, Kidd, MNS, Duffy, P1Pk, Lewis, Kell, and Lutheran blood group systems was performed on identified rare blood type donors using monoclonal antibodies. The test results are entered into the Rare Blood Type Bank Management System of the Guangzhou Blood Center, enabling functions such as confirmation reminders and cryopreservation storage when the donor donates again. Red blood cells of rare blood types are processed into frozen red blood cells for long-term storage. Results: Among voluntary blood donors, 16 cases of the ccDEE combined with Jk(a-) phenotype were identified (0.221 7%, 16/7 216); 10 cases of the ccDEE combined with Jk(b-) phenotype (0.138 6%, 10/7 216); 78 cases of the Fy(a-) phenotype (0.169 5%, 78/46 012); 39 cases of the Lu(b-) phenotype (0.138 2%, 39/28 214); 31 cases of the s(-) phenotype (0.081 8%, 31/37 913); 22 cases of the Di(b-) phenotype (0.029 9%, 22/73 691); 30 cases of the Jk(a-b-) phenotype (0.010 1%, 30/298 250); and 1 case of the k(-) phenotype (0.001 3%, 1/77 382), which was further identified as KELnull phenotype (K0). No p phenotype donors were identified (0/88 528). A total of 228 units of frozen red blood cells were prepared. The screening results were compared and analyzed with rare blood type data from other regions. Conclusion: This study, through a combination of different screening methods, significantly improved the efficiency of rare blood type screening while remaining cost-effective. By conducting large-scale screening and performing data informatization processing, a database and physical repository of rare blood types in the Guangzhou region were successfully established. This provides a strong guarantee for the timely supply of blood to patients with difficult-to-match and rare blood types in the region, effectively enhances the level of transfusion safety in the region, and offers a practical paradigm for constructing a comprehensive blood transfusion support system.
5.Effect and mechanism of Tamarix chinensis Lour.on streptozotocin-induced diabetic rats based on network pharmacology,molecular docking and experimental validation
Qian LI ; Zhenxiang WANG ; Yanting LIANG ; Weiwei MA ; Zhen ZHANG ; Xia WANG ; Qiong AN
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):907-920
AIM:To investigate the mechanism of action of Tamarix chinensis Lour.on streptozotocin-induced type 2 diabetes mellitus(T2DM)through network pharmacology,molecular docking and ex-perimental validation.METHODS:Using the TCSMP database and Swiss Target Prediction tools screen the active components and predict potential tar-gets in Tamarix chinensis Lour..Retrieving potential disease targets associated with T2DM from data-bases such as GeneCards,OMIM,and DisGeNET.The intersection targets of Tamarix chinensis Lour.and T2DM disease was obtained through Venny platform.The STRING database was used to con-structed PPI network,and Cytoscape 3.8.0 soft-ware was use to visualized.GO function enrich-ment and KEGG pathway enrichment analysis were performed through the Metascape database.Dock-ing of important target proteins and compounds was carried out by AutoDock software.SPF grade male rats were randomly divided into normal group,model group,MET group(88.5 mg/kg),TE high-dose(800 mg/kg)group,TE medium-dose(400 mg/kg)group and TE low-dose(200 mg/kg)group(n=10).High-fat and high sugar feed com-bined with low dose STZ(45 mg/kg)was used to in-duce T2DM rat model,and the rats were adminis-tered orally for 5 weeks.Fasting blood glucose(FBG),insulin(FINS)level and HOMA-IR index,bio-chemical indicators[superoxide dismutase(SOD),malondialdehyde(MDA),glycosylated hemoglobin A1c(HbA1c)and inflammatory factor[interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α),vascu-lar cell adhesion molecular(VCAM-1)levels of the rats were also observed;morphological changes of renal tissue was observe by HE staining.RESULTS:Based on the screening conditions of oral bioavail-ability(OB)≥ 30%and drug like properties(DL)≥0.18,a total of 19 main active ingredients with po-tential therapeutic effects on T2DM were screened from Tamarix chinensis Lour.,including ergosta-5,24(28)-dien-3,7,16-triol,quercetin-3,3'-dimethyl ether,kaempferol,quercetin,and others.By analyz-ing the potential targets of Tamarix chinensis Lour.for treating T2DM,a total of 185 potential target genes were screened,including SRC,EGFR,HSP90AA1,AKT1,ESR1,H1F1A,TNF,PIK3R1,etc,in-volving cancer signaling pathways,insulin resis-tance,MAPK signaling pathways,PI3K Akt signaling pathways,etc.Molecular docking results showed that the binding energies were all less than-5.0 kcal/mol,indicating that a strong binding abili-ty between the active ingredients screened by Tam-arix chinensis Lour.and the potential targets for the treatment of T2DM.The animal experiment re-sults showed that compared with the model group,the weight loss of rats in the MET and TE groups was slowed down,and the levels of FBG,FINS,MDA,HbA1c,IL-1β,TNF-α,VCAM-1,HOMA-IR in-dex were reduced,the SOD level was increased,and the differences were statistically significant(P<0.05,P<0.01),Renal tissue cellular morphology also showed notable improvement.Most importantly,all these results demonstrating dose-dependent ef-fects.CONCLUSION:Tamarix chinensis Lour.dis-plays a significant therapeutic effect on T2DM through multi-component,multi-target,and multi-pathway synergistic actions to improve blood glu-cose levels.The findings of this study provide a the-oretical basis for the clinical application of Tamarix chinensis Lour.in the treatment of T2DM.
6.Dynamic Analysis of Cardiac Magnetic Resonance Feature Tracking in Different Heart Failure Rat Models
Qi ZHU ; Rui XIA ; Boshen LIANG ; Haichen LI ; Lei XIONG ; Lei WANG ; Bojun CHEN ; Fabao GAO
Chinese Journal of Medical Imaging 2025;33(5):493-500
Purpose To explore the application value of magnetic resonance feature tracking to assess early heart failure in different rat models.Materials and Methods Fifty male SD rats were randomly divided into four groups:the control group(8 rats),the isoproterenol high dose(ISO-H)group(14 rats),the isoproterenol low dose(ISO-L)group(14 rats)and the coronary artery ligation surgery(myocardial infarction,MI)group(14 rats).The ISO-H group received intraperitoneal injections of ISO at 100 mg/kg once a week for two consecutive weeks.The ISO-L group received continuous intraperitoneal injections of ISO at 5 mg/(kg·d)for 14 days.The MI group underwent coronary ligation to establish a heart failure rat model.Scans using a 7T cardiac MRI cine sequence were performed after two weeks and four weeks.Heart function parameters and myocardial strain parameters were obtained using CVI 42 software.Serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were measured.HE staining and Masson staining were used to detect myocardial pathological changes.Results Compared with the control group,the ISO-H group,ISO-L group and MI group showed significant changes in left ventricular ejection fraction(t=-2.387,P=0.04;t=5.622,P<0.001;t=17.715,P<0.001)and overall radial strain(t=-4.570,P=0.001;t=6.587,P<0.001;t=10.649,P<0.001)after two weeks.Compared with the control group,the ISO-H group,ISO-L group and MI group showed varying degrees of reduction in left ventricular ejection fraction(t=4.834,P=0.001;t=10.325,P<0.001;t=26.286,P<0.001)and overall radial strain(t=3.890,P=0.003;t=9.547,P<0.001;t=13.751,P<0.001)after four weeks.The serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were significantly elevated(t=-93.373--11.019,P<0.001),and pathological staining revealed that all model groups exhibited varying degrees of myocardial cell hypertrophy,necrosis and interstitial fibrosis compared with the control group.Conclusion Magnetic resonance feature tracking has guiding significance for the dynamic monitoring,early diagnosis and prognosis assessment of heart failure in different rat models.
7.Construction of A Mouse Model of Liver Cancer Resistant to PD-1 Monoclonal Antibody and Analysis of Its Metabolic Changes
Xin-ru NIU ; Xia WANG ; Zhi-ting SHU ; Zi-lan XU ; Xiao-li QIU ; Wei DAI ; Liang-qian ZHANG ; Xiang-liang DENG
Progress in Modern Biomedicine 2025;25(12):1931-1941,1954
Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50%.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.
8.Clinical evaluation of daratumumab in combination with lenalidomide and bortezomib and with daratu-mumab,bortezomib,and dexamethasone for the treatment of relapsed and refractory multiple myeloma
Yuchen ZHAO ; Manting XU ; Jing BAO ; Liang XIA
The Journal of Practical Medicine 2025;41(18):2913-2919
Objective To evaluate the clinical efficacy and safety of the daratumumab-based regimens,including daratumumab,dexamethasone,and lenalidomide(DRd),as well as daratumumab,dexamethasone,and bortezomib(DVd),in the treatment of patients with relapsed or refractory multiple myeloma(RRMM)at our center.Methods Eighty patients with RRMM were assigned to either the DRd group(42 cases)or the DVd group(38 cases)based on their treatment regimens.Both groups received a baseline treatment of daratumumab combined with dexamethasone(Dd regimen).In the DVd group,1.3 mg/m2 of bortezomib was administered subcutaneously on days 1,4,8,and 11 of each cycle,followed by a 10 day drug-free interval(days 12~21),repeated every 3 weeks until disease progression.In the DRd group,25 mg of lenalidomide was orally administered daily from day 1 to day 21 of each cycle,in addition to the Dd regimen,continuing until disease progression.The two groups were compared in terms of laboratory parameters,tumor markers,clinical efficacy,safety profiles,and long-term prognostic outcomes.Results After treatment,the overall response rate(ORR)of the DRd group and the DVd group was 78.57%(33 out of 42 cases)and 52.63%(20 out of 38 cases),respectively.The serum creatinine(SCr)levels were(92.54±14.33)and(102.07±15.41)μmol/L,respectively;the M protein contents were(19.62±2.04)and(21.08±2.23)g/L,respectively;the β2-microglobulin(β2-MG)levels were(3.49±1.12)and(4.16±1.25)mg/L,respectively;and the progression-free survival rates were 42.86%(18 out of 42 cases)and 26.32%(10 out of 38 cases),respectively.All these indicators showed statistically significant differences between the DRd group and the DVd group(all P<0.05).The incidence rates of adverse reactions in the observation group and the control group were 14.29%(6 out of 42 cases)and 13.16%(5 out of 38 cases),respectively,and the difference was not statistically significant(P>0.05).Conclusion The DRd regimen demonstrates superior efficacy compared to the DVd regimen in treating patients with RRMM,leading to improved patient prognosis with a favorable safety profile.
9.Application of machine learning in the restoration of dentition defects
Xinxi YUAN ; Yekang XIA ; Han WANG ; Jian HU ; Laikui LIU ; Weiwei LIANG
STOMATOLOGY 2025;45(9):707-712,720
Machine learning,as a core branch of artificial intelligence,has gradually demonstrated significant potential in the field of dentition defect repair in recent years.By employing techniques such as data mining and pattern recognition,machine learning has been applied in various aspects including oral implant restoration,fixed bridge design,and fabrication of removable partial dentures.This paper seeks to provide a comprehensive review of machine learning applications within the aforementioned three aspects.It endeavors to assess the current developmental landscape and chart a course for future investigative endeavors,in hopes of offering a reference for re-search on machine learning in prosthodontics.
10.Molecular mechanism of active ingredients of Ligustri Lucidi Fructus against osteoporosis
Wenchi WANG ; Tian XIA ; Ruiqi WU ; Haohan LIANG ; Zhenyang NI ; Zhenhao ZHANG ; Zhenxing LI ; Guanghui CHEN ; Han SU
Chinese Journal of Tissue Engineering Research 2025;29(18):3856-3867
BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

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