OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Abstract Cholestasis can be seen in many acute and chronic liver diseases. If not intervened in time, persistent cholestasis can further progress to liver fibrosis, liver cirrhosis, liver failure, and even death. The pathogenesis of cholestasis is complex, and there is currently a lack of effective therapeutic drugs. Bile acids(BAs), the main component of bile, are synthesized from cholesterol in the liver as primary bile acids. After entering the intestine through the enterohepatic circulation, they are reshaped into secondary bile acids by gut microbiota. BAs can directly or indirectly affect the composition and function of gut microbiota, which in turn can regulate the synthesis and metabolism of BAs. The interaction between BAs and gut microbiota plays an important role in the pathogenesis and treatment of cholestasis. This review elucidates the bidirectional regulatory mechanisms between BAs and gut microbiota and their roles in the pathogenesis and treatment of cholestasis, aiming to provide insights and references for basic research and clinical practice related to cholestasis-associated diseases.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation between with the three dimensional configuration of the skin ligament.Methods:1) 12 fresh adult cadaver specimens (7 males, 5 females, aged 54-87 years) were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices, and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the midface (cheek, nose, orbital eyelid) . (2) A retrospective analysis was made of the case data of midface soft tissue defects admitted to the Plastic Surgery Department of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flap. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences of flap area and flap aspect ratio in different parts of the midface.Results:1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal The supracutaneous ligaments run down the alar of the nose. (2) The clinical study included 18 patients, 8 males and 10 females, aged (65.1±22.9) years. The flaps of 18 patients survived after operation, the flap area was (13.85±9.38) cm 2, and the advancing distance was (1.94±0.75) cm. Statistical analysis showed that there was a correlation between the flap advancement distance and the flap incision area ( r=-0.712, P=0.022) and the flap aspect ratio ( r=-0.580, P =0.012). There was no correlation with the defect area ( r=-0.227, P=0.365) ; the aspect ratios of the cheek, nose and orbital lid flaps were 2.06±0.42 , 2.50±1.18, 3.25±0.93, and the differences were statistically significant ( H= 6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing midface soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation with the three-dimensional configuration of the skin ligament.Methods:(1) Tweleve fresh adult cadaver specimens, including seven males and five females, aged 54-87 years old, were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the mid-face (cheek, nose, orbital eyelid). (2) A retrospective study was conducted with the data of mid-face soft tissue defects admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flaps. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences in flap size and aspect ratio in different parts of the mid-face. The measurement data were described by Mean±SD or M( Q1, Q3). Results:(1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal cutaneous ligaments run down the nose alar. (2) The clinical study included 18 patients, including eight males and ten females, aged (64.6±23.4) years old. All flaps survived uneventfully. The average flap size was 10.6(8.0, 18.0) cm 2, and the average advancing distance was 2.8(2.0, 4.0) cm. Statistical analysis showed a correlation between the flap advancement distance, the flap incision area ( r=-0.71, P=0.022), and the flap aspect ratio ( r=-0.58, P=0.012). There was no correlation with the defect area ( r=-0.23, P=0.365); the aspect ratios of the cheek, nose, and orbital lid flaps were 2.1(1.9, 2.3), 2.0(1.6, 3.5), 3.5(3.0, 4.0), and the differences were statistically significant ( H=6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing mid-face soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation between with the three dimensional configuration of the skin ligament.Methods:1) 12 fresh adult cadaver specimens (7 males, 5 females, aged 54-87 years) were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices, and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the midface (cheek, nose, orbital eyelid) . (2) A retrospective analysis was made of the case data of midface soft tissue defects admitted to the Plastic Surgery Department of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flap. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences of flap area and flap aspect ratio in different parts of the midface.Results:1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal The supracutaneous ligaments run down the alar of the nose. (2) The clinical study included 18 patients, 8 males and 10 females, aged (65.1±22.9) years. The flaps of 18 patients survived after operation, the flap area was (13.85±9.38) cm 2, and the advancing distance was (1.94±0.75) cm. Statistical analysis showed that there was a correlation between the flap advancement distance and the flap incision area ( r=-0.712, P=0.022) and the flap aspect ratio ( r=-0.580, P =0.012). There was no correlation with the defect area ( r=-0.227, P=0.365) ; the aspect ratios of the cheek, nose and orbital lid flaps were 2.06±0.42 , 2.50±1.18, 3.25±0.93, and the differences were statistically significant ( H= 6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing midface soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation with the three-dimensional configuration of the skin ligament.Methods:(1) Tweleve fresh adult cadaver specimens, including seven males and five females, aged 54-87 years old, were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the mid-face (cheek, nose, orbital eyelid). (2) A retrospective study was conducted with the data of mid-face soft tissue defects admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flaps. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences in flap size and aspect ratio in different parts of the mid-face. The measurement data were described by Mean±SD or M( Q1, Q3). Results:(1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal cutaneous ligaments run down the nose alar. (2) The clinical study included 18 patients, including eight males and ten females, aged (64.6±23.4) years old. All flaps survived uneventfully. The average flap size was 10.6(8.0, 18.0) cm 2, and the average advancing distance was 2.8(2.0, 4.0) cm. Statistical analysis showed a correlation between the flap advancement distance, the flap incision area ( r=-0.71, P=0.022), and the flap aspect ratio ( r=-0.58, P=0.012). There was no correlation with the defect area ( r=-0.23, P=0.365); the aspect ratios of the cheek, nose, and orbital lid flaps were 2.1(1.9, 2.3), 2.0(1.6, 3.5), 3.5(3.0, 4.0), and the differences were statistically significant ( H=6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing mid-face soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To screen and evaluate sunscreen cosmetics for sensitive facial skin.Methods:From June to August in 2019, 40 subjects with positive lactic acid sting test were recruited from the staff of Chongqing Traditional Chinese Medicine Hospital, and subjected to human skin closed patch testing with 4 kinds of sunscreen cosmetics for sensitive skin (marked as products Ⅰ, Ⅱ, Ⅲ, Ⅳ respectively) separately. Then, the 40 subjects were equally divided into 2 groups to apply 2 sunscreen products with relatively higher safety (according to the above closed patch testing results) on the face respectively. Erythema, edema and desquamation were evaluated at baseline, 2 and 4 weeks after application of the 2 products, and non-invasive measurement methods were used to detect transepidermal water loss (TEWL) , stratum corneum hydration, skin melanin content and skin sebum content. In additon, the 2 products were applied on the back of the subjects separately, and an ultraviolet solar simulator was used to determine the sun protection factor (SPF, n = 12) and protection factor of UVA (PFA, n = 11) . Measurement data were compared using paired t test and one-way analysis of variance, and nonparametric data were compared using Wilcoxon signed rank test. Results:Patch testing showed that only 1 subject developed a grade 1 reaction to the sunscreen product Ⅲ, no subjects showed positive reactions to the product Ⅳ, and the safety of products Ⅲ and Ⅳ was higher than that of the other 2 products. Subjective safety evaluation revealed that the degree of erythema after 4-week application of products Ⅲ and Ⅳ was significantly lower than that before application (Wilcoxon signed rank test, Z = 4.73, 4.82 respectively, both P < 0.05) . Objective efficacy evaluation revealed that the TEWL, stratum corneum hydration and skin melanin content significantly differed among different time points (baseline, after 2- and 4-week application of products Ⅲ and Ⅳ, all P < 0.05); after 4-week application of products Ⅲ and Ⅳ, the TEWL (30.05 ± 1.47, 30.37 ± 1.28 respectively) and skin melanin content (112.58 ± 7.34, 103.47 ± 5.48 respectively) were significantly lower than those before application (all P < 0.05) , and the stratum corneum hydration (62.35 ± 2.67, 63.72 ± 2.54 respectively) was significantly higher than that before application (both P < 0.05) . At week 4, the skin melanin content was significantly lower in the product Ⅳ group (103.47 ± 5.48) than in the product Ⅲ group (112.58 ± 7.34, t = 8.45, P < 0.05) . The SPF and PFA values of the product Ⅳ (51.8 ± 2.9, 10.1 ± 1.2 respectively) were both significantly higher than those of the product Ⅲ (31.5 ± 2.6, 7.4 ± 0.7, t = 15.34, 24.66, respectively, both P < 0.05) . Conclusion:Comprehensive application of closed patch testing, long-term application test and sun protection index determination can be used to screen and evaluate the safety and efficacy of sunscreen cosmetics for sensitive facial skin.

Objective:To analyze clinical characteristics of cosmetics-related adverse reactions and main allergenic components of cosmetics, to provide guidance for cosmetics-related adverse reaction monitoring, and to provide an objective basis for risk assessment.Methods:A total of 512 patients with suspected cosmetic adverse reactions were collected from the outpatient clinic of Chongqing Traditional Chinese Medicine Hospital from March 2018 to October 2019, including 14 males and 498 females. A uniform cosmetic adverse reaction report card was filled in, and medical history of patients and related information about the used cosmetics were recorded; 103 patients (3 males and 100 females) were subjected to patch test with their own cosmetics or cosmetic ingredients, and 48- and 72-hour patch test results were combined for comprehensive determination and analysis.Results:Among the 512 cases of suspected cosmetic adverse reactions, contact dermatitis (495 cases, 96.7%) was the most common manifestation. Cosmetic adverse reactions mainly manifested as erythema (501 cases, 97.9%), papules (313, 61.1%), edema (249, 48.6%), and scaling (166, 32.4%) ; main symptoms included itching (480, 93.8%), burning sensation (359, 70.1%), and tense sensation (297, 58.0%). Patch test with cosmetic ingredients showed positive reactions in 71 of 103 cases, and thimerosal was the allergen mostly liable to cause adverse reactions (31 cases, 30.1%), followed by sodium dodecyl sulfate (29 cases, 28.2%), Peru balsam (17 cases, 16.5%), bronopol (12 cases, 11.7%) and triethanoamine (10 cases, 9.7%). The cosmetic allergens were divided into 14 categories, and the top 4 categories with high positive patch test rates were emulsifiers (54 cases, 45.8%), preservatives (47 cases, 39.8%), fragrances (17 cases, 14.4%) and surfactants (10 cases, 8.5%). Positive patch test reactions were observed in 2 males and 69 females, and there was no significant difference in the positive rate between males and females (2/3 vs. 69/100, χ2 = 0.01, P > 0.05) ; there was also no significant difference in the positive rate among the groups aged 18 - 29 years (34%), 30 - 49 years (34%) and 50 - 70 years (32.4%; χ2 = 0.693, P > 0.05) . Conclusions:Contact dermatitis is the most common adverse reaction to cosmetics. Among the diverse allergenic components of cosmetics, thimerosal is the allergen that is mostly liable to cause adverse reactions, followed by sodium dodecyl sulfate, Peru balsam, bronopol and triethanoamine.