Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

SkinPro Ointment is an emulsion-based preparation derived from a traditional Tibetan medical empirical formula and developed using modern pharmaceutical technology. It is an exclusive patented product of Tibet Hairong Tangguo Pharmaceutical Co. Ltd. and has been listed as a National Protected Traditional Chinese Medicine Variety， the Pharmacopoeia of the People's Republic of China， and classified as a Category B product in the National Basic Medical Insurance Catalog. The ointment possesses the functions of clearing heat and drying dampness， activating blood circulation and dispelling wind， relieving itching and reducing inflammation. Clinically， it is used for skin pruritus caused by dampness-heat accumulation or blood-heat with wind-dryness， as well as pruritic skin diseases such as neurodermatitis， eczema， tinea pedis， and psoriasis. To clarify the standards for its clinical application and promote rational drug use， a consensus working group comprising 34 national experts in dermatology， evidence-based medicine， and pharmacy was established. Through expert interviews， the nominal group technique， and questionnaire surveys， 15 clinical issues were identified. The Grading of Recommendations Assessment， Development and Evaluation （GRADE） evidence grading system was employed to assess the quality of evidence， leading to the formulation of the Expert Consensus on the Clinical Application of SkinPro Ointment. This consensus specifies that the intended users are physicians and pharmacists in medical institutions at all levels. It standardizes the clinical application of the ointment， including syndrome characteristics， dosage and course of treatment， combination therapy， precautions， and contraindications. Recommendations and consensus suggestions were formed addressing the 15 clinical issues， covering the following key areas： ①Indications and TCM syndromes： In TCM， the ointment mainly treats conditions such as "damp sores" （Shichuang）， "white scaling" （Baibi）， "collar sores" （Shelingchuang）， and "damp foot Qi" （Jiaoshiqi）， corresponding to eczema， psoriasis， neurodermatitis， and tinea pedis in Western medicine. The relevant TCM syndromes are identified as dampness-heat accumulation or blood-heat with wind-dryness. ②Usage and dosage： For external use， apply to the affected area 3 times daily. The dosage should follow the fingertip unit （FTU） principle. A treatment course of 1-2 weeks is recommended for mild to moderate cases； for serious cases， the course should be followed as prescribed by a physician. ③Combined therapy： The ointment can be used as monotherapy for mild cases. For moderate to severe cases， combination therapy is recommended， with reference to relevant clinical guidelines. ④Safety： Common adverse reactions include skin rashes， pruritus， and erythema. The ointment is contraindicated in patients with broken skin or obvious exudation at the affected area， as well as in patients with known hypersensitivity to any of its components. Contact with sensitive areas such as the eyes and oral mucosa should be avoided. Modern research shows that the ointment also has potential efficacy in other dermatological conditions， such as adult atopic dermatitis， tinea cruris， exfoliative keratolysis， acne vulgaris， and Malassezia folliculitis. This consensus provides a scientific basis for promoting the rational clinical use of SkinPro Ointment， improving its therapeutic efficacy， and reducing medication risks. Future updates will be dynamically revised according to emerging clinical issues and new evidence.

Hepatocellular carcinoma （HCC） is a malignant tumor with relatively high incidence and mortality rates worldwide， and its therapeutic resistance and recurrence mechanism are closely associated with liver cancer stem cells （LCSC）. This article systematically introduces the biological characteristics of LCSC and their key role in the progression of HCC， reviews the functional characteristics of the specific surface markers （such as EpCAM and CD133） and related signaling pathways （such as Wnt/β-catenin， TGF-β， and STAT3）， elaborates on the interaction between LCSC and tumor microenvironment， and summarizes the latest clinical treatment strategies targeting LCSC and the countermeasure for existing resistance mechanisms. The article points out that LCSC promote tumor development and progression through metabolic reprogramming and immune microenvironment remodeling， and it is proposed to establish a standardized detection system for LCSC specific markers and promote a triple synergistic therapeutic paradigm combining targeted therapy， immune regulation， and traditional chemotherapy， in order to provide new ideas for the clinical intervention of HCC.

Liver cirrhosis is the final stage of the progression of various chronic liver diseases， often accompanied by serious complications and high mortality rates. Recent studies have shown that the interaction between gut microbiota and bile acid metabolism （the gut microbiota-bile acid axis） is closely associated with liver cirrhosis. This article systematically reviews the mechanism of action of the gut microbiota-bile acid axis in the progression of liver cirrhosis， elaborates on the pathological features of liver cirrhosis and its harm to the body， and summarizes the association of the gut microbiota-bile acid axis with the development and progression of liver cirrhosis. It also analyzes the key regulatory role of this axis in the progression of liver cirrhosis and explores its potential application value as a therapeutic target for liver cirrhosis， in order to provide a theoretical basis for exploring more effective clinical intervention methods.

Objective:To investigate the effect of COX6C on the proliferation of multiple myeloma(MM)cells and its mechanism of action.Methods:The expression of COX6C in MM cell lines were detected by RT-PCR.siRNA technology was used to knockdown COX6C expression in OPM2 cells.MTT assay and flow cytometry were employed to assess the effect of COX6C knockdown by siRNA on cell proliferation,mitochondrial membrane potential(Δ Ψm),and intracellular adenosine triphosphate(ATP)levels.The mitochondrial morphological changes in OPM2 cells pre-and post-siRNA-mediated COX6C knockdown were observed by transmission electron microscopy(TEM).Results:The relative expression level of COX6C was significantly increased in MM cell lines(P＜0.01).Following siRNA-mediated COX6C knockdown,OPM2 cell proliferation was inhibited,with viable cells accounting for 62.32％±3.43％and 47.01％±5.12％after 48 and 72 hours of culture,respectively.siRNA-mediated COX6C knockdown also caused significant reductions in mitochondrial membrane potential and intracellular ATP levels(P＜0.05),accompanied by mitochondrial shortening,swelling,and incomplete cristae structures.Conclusion:COX6C may promote the proliferation of MM cells by altering the mitochondrial structure and elevating intracellular ATP levels.

Objective:To analyze the surveillance results of brucellosis in Shanxi Province, to gain a understanding of the epidemic characteristics and changing trend of brucellosis in Shanxi Province, and to provide scientific basis for formulating prevention and control strategies and measures for brucellosis.Methods:The surveillance data of brucellosis in Shanxi Province from Infectious Disease Reporting Information Management System of China Disease Prevention and Control Information System, and the active surveillance results of 5 national brucellosis surveillance sites from 2018 to 2023 were collected for descriptive analysis.Results:From 2018 to 2023, a total of 24 041 cases of human brucellosis were reported in Shanxi Province, with the number of cases increased from 2 800 in 2018 to 5 131 in 2023. The annual reported incidence was 11.22/100 000, ranging from 7.56/100 000 to 14.74/100 000, showing an overall upward trend (χ 2trend = 1 377.43, P < 0.001). The epidemic had affected all counties (cities and districts) in the province, mainly concentrated in Linfen City, Jinzhong City, Datong City, and Shuozhou City, with a total of 13 489 cases of human brucellosis reported, accounting for 56.11%. The population distribution was mainly composed of individuals aged 40 - 69 (17 682 cases), males (18 513 cases), farmers (20 295 cases), and household and unemployed individuals (1 017 cases). The onset of the disease showed obvious seasonality, with the peak time from March to August, accounting for 66.39% (15 961/24 041). A total of 14 130 occupational individuals were investigated at the surveillance sites, and 11 141 underwent serological tests, with a positive rate of 5.25% (585/11 141), including 299 new cases. The positive rate of serological tests was relatively high in Qinyuan County, at 8.51% (241/2 832). Etiological culture was conducted on 338 human blood samples, and 43 strains of Brucella were isolated, with a detection rate of 12.72%. All strains were Brucella melitensis, including 42 strains of Brucella melitensis biovar 3. Conclusions:The overall trend of human brucellosis epidemic in Shanxi Province from 2018 to 2023 is on the rise, and it is still at a high level. It is suggested to continue strengthening monitoring, study the epidemic situation in a timely manner, take comprehensive prevention and control measures, and effectively control the spread of brucellosis.

Objective:To investigate the prevalence of skeletal fluorosis and the management and treatment of patients in endemic fluorosis areas of Shaanxi Province.Methods:From March to November 2023, in accordance with the requirements of the "2023 Monitoring Plan for Endemic Fluorosis in Shaanxi Province", the implementation of prevention and control measures of endemic fluorosis in Shaanxi Province was investigated. The data of patients with skeletal fluorosis from January to December 2023 were downloaded from Shaanxi Province Endemic Disease Control Information Management Platform, and the epidemiological characteristics were analyzed. At the same time, the management and treatment of patients with skeletal fluorosis in endemic fluorosis areas of Shaanxi Province were carried out in accordance with the requirements of the "Shaanxi Province Endemic Disease Patient Management Service Specification".Results:In 2023, there were 10 drinking water-borne endemic fluorosis cities in Shaanxi Province, involving 3 715 endemic villages, including 3 650 water improvement villages with a water-improving rate of 98.25%. There were 2 coal-burning-borne endemic fluorosis cities in Shaanxi Province, involving 641 746 households in 1 414 endemic villages. Among them, 641 617 households had changed their furnaces and stoves, with a furnace and stove change rate of 99.98%. There were 37 462 patients with skeletal fluorosis in the province, with 35 792 from drinking water-borne endemic fluorosis areas and 1 670 from coal-burning-borne endemic fluorosis areas. The condition was mainly mild and moderate (94.12%, 35 258/37 462), with females accounting for 55.13% (20 654/37 462). The education level was mainly primary school and illiteracy (83.64%, 31 333/37 462), and the occupation was mainly farmers (99.29%, 37 196/37 462). A total of 37 116 patients with skeletal fluorosis were followed up and managed, with a management rate of 99.08% (37 116/37 462). A total of 35 756 patients were managed in a standardized manner, and the standardized management rate was 96.34% (35 756/37 116). A total of 30 649 patients with skeletal fluorosis were actually treated, with a treatment rate of 84.27% (30 649/36 370) and a total effective rate of 98.08% (30 062/30 649).Conclusion:In 2023, the prevalence of skeletal fluorosis in endemic fluorosis areas of Shaanxi Province is mainly mild and moderate, with a wide coverage of community management and a high level of treatment efficiency.

Objective To investigate the differences in demographic characteristics,reproductive health status,and the distribution of pregnancy-related diseases between couples conceived via assisted reproductive technology(ART)and naturally conceived couples,and to analyze the impact of ART treatment on the incidence of preterm birth(PTB)in singleton and twin and multiple pregnancies.Methods We conducted a retrospective analysis of the maternal and infant cohort data of Jing'an District from 2013 to 2020.Based on the conception method,the subjects were categorized into two groups:the ART group and the natural conception group.Chi-square test was applied to compare baseline characteristics and disease distributions differences between the two groups,and logistic regression models were used to evaluate the association between ART and the PTB risks.A causal mediation model was used to evaluate the mediating effect of twin and multiple pregnancy in the relationship between ART and PTB.Results A total of 117 717 parturients were included,6 265 in the ART group and 111 452 in the natural conception group.Compared with the natural conception group,couples in the ART group were significantly older and had a higher prevalence of reproductive system diseases.The incidences of diabetes and hypertensive disorders during pregnancy in ART parturient were 13.76%and 9.99%,respectively,which were significantly higher than 7.88%and 4.75%in the natural conception group(both P<0.001).The overall PTB rate in the ART group was 14.81%,higher than 5.35%in the natural conceptions group(P<0.001).The PTB rate in ART for singleton pregnancies in the ART group was 6.40%,higher than 4.83%in the natural conception group(P<0.001),while the PTB rate in ART for twin and multiple pregnancies in the ART group was 53.97%,lower than 60.42%in the natural conception group(P<0.05).Mediation analysis showed that 97.99%of the effect of ART on PTB was mediated by twin and multiple pregnancy,with ART increasing the PTB risk by 3.44 times through multiple pregnancy.Conclusion The overall PTB rate of ART recipients is higher than that of natural recipients,but ART does not increase the PTB risk in singleton and twin and multiple pregnancies.Twin and multiple pregnancy is the key mediating factor contributing to PTB in ART-conceived recipients.Compared with naturally conceived couples,ART conception couples own more advanced maternal age,and have higher risks of suffering gestational diabetes,gestational hypertension,and PTB.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.