BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVE: To compare early graft healing between over-the-top (OTT) and anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. METHODS: A clinical data of 40 patients underwent ACL reconstruction, who admitted between June 2021 and October 2022 and met the selective criteria, was retrospectively analyzed. Among them, 20 patients were treated with OTT reconstruction (OTT group) and 20 with SB reconstruction (SB group). There was no significant difference between groups ( P>0.05) in the gender, age, affected side, disease duration, degree of meniscus injury, body mass index, and preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, pain visual analogue scale (VAS) score, and KT-2000 measurement. At 3, 6, and 12 months, MRI was performed to measure the signal noise quotient (SNQ) of the proximal end, middle, and distal end of the graft in the two groups, as well as at the corner of the graft with lateral femoral condyle and 1 cm around the femoral fixation point in the OTT group, to observe the degree of graft healing. Before operation and at 3, 6, and 12 months, the knee function and pain were evaluated by IKDC score, Lysholm score, and VAS score. Before operation and at 12 months after operation, the KT-2000 measurement was taken to evaluation the knee joint stability. RESULTS: All operations were successfully completed in both groups and the incisions healed by first intention. All patients were followed up 12-15 months (mean, 12.9 months), with no significant difference in the follow-up time between groups ( P>0.05). After operation, the IKDC score, VAS score, and Lysholm score improved gradually over time in both groups, with significant differences between different time points ( P<0.05). The differences between groups at 3, 6, and 12 months after operation were not significant ( P>0.05). The anterior and posterior stability of the knee joint improved significantly in both groups at 12 months after operation, and the difference in KT-2000 measurements was significant when compared with the preoperative value ( P<0.05), but the difference of pre- and post-operation between groups was not significant ( P>0.05). At 3, 6, and 12 months after operation, MRI showed that the differences in the SNQ of the proximal end and middle of the grafts between the two groups were not significant ( P>0.05), and the SNQ of distal end was significantly higher in the SB group than in the OTT group ( P<0.05). At each time point, grafts in the OTT group had the highest SNQ at the corner and the lowest at the fixation point, and the differences were significant compared to the other sites ( P<0.05). In the two groups, except for the fixation point, the SNQ of the remaining sites were highest at 6 months and lowest at 12 months ( P<0.05). In addition, there were significant differences in SNQ between the different sites of grafts ( P<0.05), and the SNQ was lowest at proximal end and highest at distal end. At last follow-up, the knee grafts in both groups were in good shape and no graft necrosis or loosening of the internal fixation was observed. CONCLUSION The knee joint function and graft healing after OTT reconstruction of ACL are similar to those of SB reconstruction, but it should be noted that the healing at the corner of the graft is slower.
Retrospective Studies ; Treatment Outcome ; Anterior Cruciate Ligament Reconstruction/rehabilitation* ; Follow-Up Studies ; Tibial Meniscus Injuries/surgery* ; Patient Positioning/methods* ; Recovery of Function ; Pain Measurement ; Knee Joint/surgery* ; Humans ; Male ; Female ; Adult ; Wound Healing

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

In accordance with the theory of'treating the skin diseases with the skin',skin-related Chinese medicinals are usually used for the treatment of skin diseases,which reflects the thinking mode of holistic syndrome differentiation and classification according to the manifestations in traditional Chinese medicine.With ying-yang theory as the principle of differentiation and treatment of diseases and based on the core pathogenesis of'yin-yang imbalance causing the manifestations of the skin'for the skin diseases,Chinese medical master XU AN Guo-Wei has used skin-related Chinese medicinals in the treatment of skin diseases and has given full play to their unique advantage by following the theory of'treating the skin diseases with the skin'and'balanced regulation of yin and yang'.In the clinical practice,allergic skin diseases were usually treated with Cicadae Periostracum plus Dictamni Cortex for dispelling wind and relieving itching,hypopigmentation related skin diseases were usually treated with Sojae Semen Nigrum skin plus Dictamni Cortex for dispelling wind and tonifying kidney,autoimmune skin diseases were usually treated with Moutan Cortex plus Lycii Cortex for nourishing yin,clearing heat and activating blood,and skin diseases associated with abnormal sebum secretion were usually treated with Mori Cortex plus Lycii Cortex for purging lung and nourishing kidney.Skin-related Chinese medicinals have the actions of expelling wind and promoting eruption of papules,tonifying kidney and nourishing yin.The medication method of'treating the skin diseases with the skin'will provide reference for the treatment of skin diseases.

Objective To observe the clinical efficacy of Bazhen Decoction combined with traumatic medicated gauze(prepared mainly with the herbs of Scutellariae Radix,Phellodendri Chinensis Cortex and Sanguisorbae Radix)in the treatment of patients with diabetic foot ulcer(DFU)of qi-blood deficiency syndrome.Methods A total of 42 cases of DFU patients with qi-blood deficiency syndrome were randomly divided into a control group and an observation group,with 21 cases in each group.The control group was given basic western medicine treatment combined with external application of traumatic medicated gauze on wound surface,while the observation group was treated with Bazhen Decoction orally on the basis of treatment for the control group,and the treatment course of both groups covered four weeks.The changes of wound area,traditional Chinese medicine(TCM)syndrome scores,ankle-brachial index(ABI),and serum levels of fibrinogen(FIB),C-reactive protein(CRP),tumor necrosis factor α(TNF-α)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety in the two groups were compared.Results(1)After four weeks of treatment,the total effective rate in the observation group was 95.24%(20/21)and that in the control group was 85.71%(18/21),and the intergroup comparison(by rank sum test)showed that the clinical efficacy in the observation group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the wound area and TCM syndrome scores in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement of the wound area and TCM syndrome score in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,ABI in the two groups was increased when compared with that before treatment(P＜0.05),and the improvement of ABI in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum CRP,TNF-α and FIB in the two groups were all decreased compared with those before treatment(P＜0.05),and the improvement of the serum levels in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment,there were no significant adverse reactions occurring in the two groups,with high safety.Conclusion Bazhen Decoction combined with traumatic medicated gauze exerts certain effect in the treatment of DFU patients with qi-blood deficiency syndrome.The combined therapy is effective on improving the coagulation function and lower limb ischemia,reducing the levels of inflammatory factors,and relieving the inflammatory reaction,without obvious adverse reactions.

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

Objective:To observe the efficacy of using electroacupuncture(EA)plus stuck-needle lifting method to treat intractable facial paralysis based on the myofascial theory. Methods:Ninety patients with intractable facial paralysis were divided into a control group and an observation group using the random number table method,with 45 cases in each group.The control group was given conventional EA treatment,and the observation group received EA plus the stuck-needle lifting method based on the myofascial theory for 4 consecutive weeks,6 sessions each week.The electromyographic results,modified Portmann scale(MPS)score,facial nerve function index(FNFI),and total effective rate were compared. Results:There were no significant differences in the MPS and FNFI scores between the two groups before treatment(P>0.05).After treatment,the total effective rate and FNFI and MPS scores were notably higher in the observation group than in the control group(P<0.05).There were no significant differences in the electromyographic readings between the two groups before the intervention(P>0.05).After the intervention,the observation group had a shorter blink reflex R1 latency and a higher facial nerve compound muscle action potential compared with the control group,and the between-group differences were statistically significant(P<0.05). Conclusion:EA plus stuck-needle lifting method based on the myofascial theory can enhance treatment efficacy for intractable facial paralysis.

Objective:To discuss the point-selection and point-grouping patterns and therapeutic application features in acupuncture-moxibustion treatment of acute gouty arthritis(AGA)based on complex networks and to provide references for treating AGA with acupuncture-moxibustion therapy. Methods:Articles related to acupuncture-moxibustion treatment of AGA were searched across the China National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Data Knowledge Service Platform(Wanfang),Chinese Biomedical Literature Service System(SinoMed),PubMed,Web of Science(WOS),and Excerpta Medica Database(EMBASE)from their inception till March 31,2023.An acupuncture-moxibustion prescription database was established after the articles were screened according to the inclusion and exclusion criteria.The association rule and complex network analyses of points were conducted using SPSS Modeler 18.1 and Gephi 0.9.7. Results:A total of 145 articles were collected,contributing 382 pieces of acupuncture-moxibustion prescriptions involving 104 points with a total frequency of 1 288.Ashi points contributed the highest frequency.The Spleen Meridian of Foot-Taiyin and the Stomach Meridian of Foot-Yangming were more commonly selected.Filiform-needle acupuncture and bloodletting therapy were more frequently used.The association rule analysis revealed that the highest degree of support belonged to"Ashi point-Zusanli(ST36)"and"Sanyinjiao(SP6)-Zusanli(ST36)",which reflected the rules of point combination of distal and proximal areas and point combination of the coupled meridians.The complex network analysis of the major points discovered a core point prescription mainly consisting of Ahi point,Zusanli(ST36),Sanyinjiao(SP6),Yinlingquan(SP9),and Taichong(LR3).Pattern differentiation and region differentiation were used in selecting adjunct points,stressing the improvements of patterns and joint-related symptoms. Conclusion:Acupuncture-moxibustion treatment of AGA follows the principle of combining major points with adjunct points selected based on pattern or region differentiation;the selection of major points focuses on regulating the deficient Zang-Fu organs,and the selection of adjunct points emphasizes improving patterns and symptoms.The specificity of therapeutic effects is also stressed.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.