Expert consensus on the technical specifications of the in vitro skin penetration test of cosmetic product by Franz diffusion cell

Background:Diffusion cell test is one of the most commonly used in vitro model to detect the percutaneous absorption of cosmetic ingredients.Although PRC State Administration of Quality Supervision and Quarantine has issued the guideline for the in vitro test method for the percutaneous absorption of drug molecules,there is still a lack of guideline for the percutaneous absorption test of cosmetic components.Objective:In order to improve the standardized level and make the in vitro percutaneous absorption test of cosmetic ingredients more comparable,based on the international and domestic experience,Transdermal Drug Delivery Committee of the World Federation of Chinese Medicine Societies organized the experts to discuss and formed this consensus as reference for the percutaneous absorption test of cosmetic components.Materials and Methods:To standardize the in vitro diffusion cell test technique for transdermal penetration of functional cosmetic ingredients,the Transdermal Drug Delivery Professional Committee of the World Federation of Societies of Traditional Chinese Medicine has organized many discussions among experts.

Multifunctional nanoparticle-mediated combining therapy for human diseases

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

A piezoelectric-driven microneedle platform for skin disease therapy

With over a million cases detected each year,skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate,propensity for recurrence,and potential for post-treatment scarring.Photodynamic therapy(PDT)is a treatment with minimal invasiveness or scarring and few side effects,making it well tolerated by patients.However,this treatment requires further research and development to improve its effective clinical use.Here,a piezoelectric-driven microneedle(PDMN)platform that achieves high efficiency,safety,and non-invasiveness for enhanced PDT is proposed.This platform induces deep tissue cavitation,increasing the level of protoporphyrin IX and significantly enhancing drug penetration.A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT(PDMN-PDT).Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25%and 50%,respectively,without any anesthesia compared to traditional PDT.These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment,which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

The Mechanism and Influence of AKAP12 in Different Cancers

The development of cancer is a complex process that requires the participation of many factors,including mutations in genes, regulation of signaling pathways, disruption of homeostasis, and failure of self-monitoring mechanisms. Sufficient evidence has

Number of parous events affects the association between physical exercise and glycemic control among women with gestational diabetes mellitus:A prospective cohort study

Background:Multiparous women are at a higher risk of gestational diabetes mellitus(GDM) than primiparas.Physical activity during pregnancy has been shown to be beneficial for GDM,but there is little evidence on the association between physical activity and glycemic control among women with GDM,whether primiparas or multiparas.Thus,the objective of the present study was to examine the association between physical activity and glycemic control in women with GDM and to determine what,if any,effects result from number of parous events.Methods:A prospective cohort of 1162 women with GDM was recruited,with 604 multiparas(51.98%).The general linear model was used to calculate the risk difference and its 95% confidence interval(95%CI) to quantify the impact of parous events on glycemic control in pregnancy as well as the association between physical activity time and glycemic control.Results:Among 1162 women with GDM,the median daily activity time was 65 mm(interquartile range(IQR):45-90 min),and the abnormal plasma glucose(PG) percentage,calculated as number of abnormal PG tests divided by the total number of PG tests,was 40.00%(IQR:22.22%-66.67%).The percentage of abnormal PG was stabilized and statistically lower with daily physical activity time exceeding 60 min among primiparas(IQR:30.89%-44.43%) and exceeding 90 min among multiparas(ranged from 27.76% to 38.82%).After adjusting for potential confoumders,primiparas tended to have a lower percentage of abnormal PG than do multiparas(rate difference=-0.39,95%CI:-3.61 to2.84).The same amount of physical activity time was significantly less effective for multiparas than for primiparas(trend p-value <0.01).Conclusion:In women with GDM,being multiparous is associated with less effective glycemic control through physical activity,such that multiparas need more physical activity to achieve glycemic control at a similar level to primiparas.

Novel intense pulsed light-photodynamic therapy strategy in the treatment of facial actinic keratoses concomitant with rosacea

Rosacea presents as transient or persistent erythema,papules,pustules,fAushing,and telangi-ectasia on the middle of the face,which has some clinical similarity with act inic keratosis(AK).These two conditions can coexist in the same patient.Dermoscopy and reflect ance confocal microscopy(RCM)could be useful methods for diagnosis and monitoring treatment efficacy.Novel intense pulsed light-photodynamic therapy(IPL-PDT)may have better tolerance and curative effect than traditional red-light 5-aminolevulinic acid photodynamic therapy(ALA-PDT).Herein,we present a case of facial AKs concomitant with rosacea where combination therapy of novel IPL-PDT and oral minocycline was effective in that AK lesions were eliminated and the patient's facial erythema and telangiectasia were significantly improved.

Liposomes and liposome-like nanoparticles:From anti-fungal infection to the COVID-19 pandemic treatment

The liposome is the first nanomedicine transformed into the market and applied to human patients.Since then,such phospholipid bilayer vesicles have undergone technological advancements in delivering small molecular-weight compounds and biological drugs.Numerous investigations about liposome uses were conducted in different treatment fields,including anti-tumor,anti-fungal,anti-bacterial,and clinical analgesia,owing to liposome's ability to reduce drug cytotoxicity and improve the therapeutic efficacy and combinatorial delivery.In particular,two liposomal vaccines were approved in 2021 to combat COVID-19.Herein,the clinically used liposomes are reviewed by introducing various liposomal preparations in detail that are currently proceeding in the clinic or on the market.Finally,we discuss the challenges of developing liposomes and cutting-edge liposomal delivery for biological drugs and combination therapy.

Treatment of cutaneous lichen planus with ALA-mediated topical photodynamic therapy

Purpose:To evaluate the efectiveness of topical 5-aminolevulinie acid(ALA)-mediated pho-todynamic therapy(PDT)for the treatment of cutaneous lichen planus(LP).Methods:A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed.ALA cream(10%)was applied topically to LP lesions for 3h.The lesions were iradiated with a 635 nm diode laser at the dose level of 100J/cm^(2).The treatment was repeated at two week intervals.Clinical assessmnent was conducted before each treatment.Follow-up was performed once a month for up to six months.Results:Lesions showed significant improvement after one to four courses of treatments.Complete response was achieved in 13 lesions(five patients)and partial remission in four lesions(two patients).The complete response rate was 71%.There was no significant side ffects except the feeling of pain that most patients could tolerate.Follow-up of five patients who achieved complete response showed no signs of recurrence.Conclusion:Topical ALA PDT is effective in the treatment of cutaneous LP.

Ageing-Related Features of Hair and Scalp in Chinese Women by Clinical Evaluation Study

There are previous studies of ageing hair and scalp in Caucasians and some Asians, such as Koreans and Japanese. However, the characteristics of scalp and hair have not yet been studied in Chinese, the largest population in the world, especially in terms of ageing. The purpose of this study is to investigate ageing features in Chinese women’s hair and scalp. Methods: In total, 1343 women in China aged 20 to 65 participated in this research. Hair density and diameter were measured and analysed with Folliscope&reg. Hair color and scalp conditions such as dandruff and erythema were evaluated through microscopic images. Measuring equipment was also used to detect scalp water content, barrier function and sebum secretion. Results: Hair density decreased gradually with ageing, while hair diameter peaked at 40s. The color of hair became bright with ageing because of gray hair and color fading. The degree of scalp sebum and dandruff was higher at younger ages. Interestingly, scalp erythema became more severe with ageing. Conclusion: This study shows the physical and physiological changes of Chinese women’s hair and scalp. Most aging features (hair diameter, scalpsebum contents, dandruff and erythema) were noticeable in their 40s, but hair density began to decline in their 30s. This first study of aging hair and scalp in Chinese women would be helpful for understanding the ageing phenomenon and development of hair and scalp care products.

A study of storage conditions for pre-mashed fried Semen Zizyphi Spinosae using a multi-factor orthogonal design

Background:To facilitate the preparation of traditional Chinese medicines they are pre-mashed,i.e.,mashed in advance.However,storage conditions for pre-mashed traditional Chinese medicines are based on subjective judgments of pharmacists,and the best storage conditions have not generally been determined.Semen Zizyphi Spinosae is a commonly used traditional Chinese medicine,and it is usually used after it is fried.The medicine needs to be mashed in a timely manner to ensure its effectiveness.The Chinese Pharmacopoeia provides a limit for its aflatoxin content.Methods:The orthogonal experimental design method optimizes the best plan for pre-mashed fried Semen Zizyphi Spinosae.Experimental conditions were defined using the L^(9)(3^(4))orthogonal design table.Four factors and three levels were used to study storage conditions.The four factors and three levels are as follows:storage temperature(10°C,20°C,and 30°C),storage humidity(45%,60%,and 75%),storage times(10,20 and 30 days),and particle sizes for the powder(coarsest,coarse and medium powders).The contents of jujuboside A,spinosin,aflatoxin B1,total aflatoxins(aflatoxins B1,B2,G1,and G2),moisture,total ash,acid value,and saponification values were measured.Results:The results demonstrated that the highest jujuboside A and spinosin contents were obtained using a storage temperature of 20°C,a storage humidity of 75%,a storage time of 10 days,and with a coarse powder particle size.Aflatoxin B1 and total aflatoxins(aflatoxins B1,B2,G1 and G2)were not detected under these conditions.Conclusion:There is no requirement for traditional Chinese medicines to be pre-mashed.This study evaluated various storage conditions for pre-mashed fried Semen Zizyphi Spinosae,and considered the influence of four factors on the contents of jujuboside A,spinolin and aflatoxin for quality control to provide a reference for other pre-mashed traditional Chinese medicines.

Cutaneous allergic reaction to subcutaneous vitamin K_(1):A case report and review of literature

BACKGROUND Vitamin K1(phytomenadione)is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders.Adverse cutaneous reactions to vitamin K1 can occur;however,owing to its low incidence and considerable variability in presentation and morphology,its diagnosis can be easily overlooked.Managing these reactions may be challenging for patients and clinicians.Therefore,reviewing the adverse cutaneous reactions to vitamin K1 is important.CASE SUMMARY Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site.The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids.Eczema was diagnosed based on the results of the pathological examination,immunohistochemical staining,and a skin biopsy.The patient was advised to take herbal medicines orally twice daily.After treatment and follow-up,the patient’s eczematous urticarial plaques improved and her condition stabilized.CONCLUSION Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

Acne conglobata(AC),perifolliculitis capitis abscedens et suffodiens(PCAS)and hidradenitis suppurativa(HS)are uncommon refractory chronic,inflammatory,scarring diseases but cause serious damage to the quality of life.These three diseases are associated with follicular occlusion.Several studies indicated topical 5-aminolevulinic acid photodynamic therapy(ALA-PDT)improved follicular occlusion besides acne treatment.So we attempted to apply ALA-PDT to medicine resistant AC,PCAS and HS.Topical ALA-PDT was applied to 10 patients with AC,seven patients with PCAS and three patients with HS for more than three sessions.All the patients completed the dermatology life quality index(DLQI)questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment.Adverse effects were recorded at each visit.The results showed 25.5%(5/20,two cases of AC and three cases of PCAS)of patients achieved excellent improvement after three sessions of PDT and another 60.0%(12/20,eight cases of AC and four cases of PCAS)of patients achieved good improvement.15.0%(3/20,three cases of HS)got poor response(<20%lesions clearance).Anotherfive cases(three cases of AC and two cases of PCAS)also achieved excellent response after 5–7 sessions of PDT.We also found that papular/nodular,cyst/abscess showed higher clearance rate than sinus/¯stula(88.5%,86.1%versus 11.1%).DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients.5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS.The e±cacy increased with more treatment sessions.

Anesthetic injection pain and hematoma occurrence during upper blepharoplasty:Comparison between thin needles and thick needles

Background:Upper blepharoplasty is one of the most commonly performed esthetic surgeries,but injection pain during local anesthesia often disturbs patients.The objective of this study was to identify the pain levels associated with anesthetizing the upper eyelids in blepharoplasty and determine whether injection with thin needles is associated with less pain and bleeding than injection with thick needles.Methods:The study included 50 patients who underwent bilateral upper blepharoplasty.The eyelids were anesthetized using 2%lidocaine with 1:100000 epinephrine.One upper eyelid was randomly injected with a thin needle(26G)and the other with a thick needle(22G).The pain level was scored by patients immediately after the injection of each eyelid using a visual analog scale(VAS)ranging from 0 to 10.The incidence of eyelid hematomas caused by the anesthetic injection was also recorded.Results:The VAS scores in eyelids injected with thin needles were not significantly lower than those in eyelids injected with thick needles(4.0 vs.4.0,P=0.393).The formation of eyelid bruises caused by thin-needle injection was less frequent than that caused by thick-needle injection(16%vs.26%),but there was no significant difference between the two groups(P=0.326).Conclusion:Using thin needles for local anesthesia during upper blepharoplasty could not significantly decrease injection pain or hematoma occurrence compared with that associated with using thick needles.

Impact of Adverse Events Associated With Acitretin Treatment of Moderate-to-Severe Plaque Psoriasis:Based on an Observational,Single-Center Study in Shanghai,China

Objective:Acitretin is a widely used systemic retinoid that is to treat psoriasis but has significant variations in efficacy and adverse events(AEs)among individuals.This study aimed to determine the impact of AEs associated with acitretin treatment of moderate-to-severe plaque psoriasis on the Dermatology Life Quality Index(DLQI)and Hospital Anxiety and Depression Scale(HADS)scores.Methods:This prospective,observational,single-center study was conducted from March 2021 to June 2022 and analyzed 116 patients with moderate-to-severe plaque psoriasis treated with acitretin who were followed up for 12 weeks.The primary outcome was the incidence of AEs related to acitretin,and the secondary objective was to investigate the effect of AEs on the DLQI and HADS scores.The generalized linear models were used to assess the association between AEs related to acitretin and DLQI scores or HADS scores,and the association between the involved system/tissue and DLQI scores or HADS scores.Results:A final total of 45 patients were included in the analysis,and a total of 157 treatment-related AEs involving nine organs or systems were reported in 41 patients.The most common AE was skin-or mucosa-related,with 72 cumulative events in 31 patients.AEs also commonly affected the endocrine,digestive,and genitourinary systems.Compared with the group with 0-2 AEs,the group with 3-5 AEs had a significantly increased DLQI score by 5.49 points(95%CI,1.47-9.51)(P=0.0089).Compared with AEs involving 0 to 1 system,AEs affecting 2 to 3 systems resulted in a significant increase in the DLQI score by 5.75 points(95%CI,1.67-9.83)(P=0.0071).Generalized linear models showed no statistically significant associations between AEs and the HADS scores.Conclusion:Our study demonstrates a high incidence of acitretin-related AEs.These AEs may affect quality of life but rarely cause psychological problems such as anxiety and depression.

β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis

Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.Methods:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number table.Histopathological changes in vivo were assessed by hematoxylin and eosin staining.Ratios of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow cytometry.Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.Results:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P<0.01).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23,tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P<0.01 or P<0.05).Furthermore,it reduced the number of γδ T17 cells in skin lesion of mice and draining lymph nodes(P<0.01).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine expression.It inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

Julolidinyl aza-BODIPYs as NIR-Ⅱ fluorophores for the bioimaging of nanocarriers

The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences.However,its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-Ⅰ(700-900 nm)bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence.This study aimed to develop ACQ-based NIR-Ⅱ(1000-1700 nm)probes to further improve the imaging resolution and accuracy.The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects.The newly developed probes displayed remarkable photophysical properties,with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region.Compared with the NIR-Ⅰ counterpart P2,the NIR-Ⅱ probes demonstrated superior water sensitivity and quenching stability.ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation.Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties.Additionally,in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1,in contrast to 15% for P2.

Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and biodegradability.However,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal formulations.To address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,respectively.All liposomes show high stability and drug loadings,as well as sustained drug release.The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal PTX.Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX.Among all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion rate.Witnessing its superior safety,PTX-PA liposomes hold potential for further clinical translation.

Oral delivery of insulin by barbed microneedles actuated by intestinal peristalsis

Oral formulations are always preferred to injections due to the advantages of high patient compliance,no biohazardous needle waste,and low requirements for administration skills.However,the presence of multiple gastrointestinal(GI)barriers,including extreme gastric acidity and a broad pH gradient,digestive enzymes,thick and variable mucus layers,and tight junctions in the enteric epithelia,restricts the rate and extent of oral absorption.Only active ingredients with favorable physicochemical properties.

Efficacy and safety of Huzhang Granule,a compound Chinese herbal medicine,for acute gouty arthritis:A double-blind,randomized controlled trial

Background:Acute gouty arthritis(AGA)is an inflammatory joint disease with a high prevalence.Typical medical interventions,including nonsteroidal anti-inflammatory drugs,colchicine and glucocorticoids,can have serious adverse reactions.Huzhang Granule(HZG),a compound Chinese herbal medicine,has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions.However,the efficacy and safety of HZG in AGA patients remains unknown.Objective:The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients.Design,setting,participants and interventions:The current study was conducted as a noninferiority,randomized controlled clinical trial on 180 eligible enrolled participants.Participants were randomly assigned into the HZG and etoricoxib groups.Treatments were administered for 5 d,during which the HZG group received HZG and placebo etoricoxib,while the etoricoxib group received etoricoxib and placebo HZG in the same ratio(1:1).Main outcome measures:The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window.The pain level was measured via a visual analogue scale,ranging from 0 mm to 100 mm.The secondary outcomes comprised joint tenderness and swelling,reduction of inflammatory biomarkers,and the patient’s and investigator’s global evaluations of therapeutic response.Results:The mean reduction in pain was-51.22 mm(95%confidence interval[CI],[-53.42,-49.03]mm)for the HZG and-52.00 mm(95%CI,[-54.06,-49.94]mm)for the etoricoxib groups.The mean difference between the two groups was 0.78 mm(95%CI,[-2.25,3.81]mm).All additional efficacy endpoints,covering decreased inflammation and pain relief,yielded compelling proof of noninferiority.Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group(4.44%vs 13.33%;P≤0.05).Conclusion:HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness.The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA.