Objective:To investigate the expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea and their clinical significance.Methods:A prospective study included 65 patients with rosacea from the Department of Dermatology, Sichuan Provincial People＇s Hospital, from May to October 2022. There were 8 males and 57 females with an average age of (30.9±9.8) years, including 47 cases of erythematotelangiectatic type and 18 cases of papulopustular type. Twenty healthy individuals from the same hospital＇s physical examination during the same period were included as control group, consisting of 3 males and 17 females with an average age of (33.8±10.0) years. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum KLK5, IL-17, and IL-18. Investigator＇s global assessment (IGA) score was used to assess the severity of papules and pustules, and clinical erythema assessment (CEA) score was used to assess the severity of persistent erythema. The expression levels of serum KLK5, IL-17, and IL-18 were compared between the two groups, and the correlation between the severity of the disease and the expression levels of KLK5, IL-17, and IL-18 was analyzed. Additionally, the expression levels of KLK5, IL-17, and IL-18 in different subtypes of rosacea were compared.Results:The expression levels of serum KLK5, IL-17, and IL-18 in the rosacea group were (3134.01±448.82), (154.78±37.64), (236.24±38.81) pg/ml, respectively, all of which were higher than those in the healthy control group (2421.54±340.07), (95.36±24.94), (181.61±23.88) pg/ml, with statistically significant differences (all P<0.05). The levels of serum KLK5, IL-17, and IL-18 in patients with rosacea were positively correlated with IGA scores ( r=0.534, 0.767, 0.417) and CEA scores ( r=0.852, 0.459, 0.309) (all P<0.05). There were no statistically significant differences in the expression levels of serum KLK5, IL-17, and IL-18 between the erythematotelangiectatic and papulopustular subtypes of rosacea (all P>0.05). Conclusions:The expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea are higher than those in the healthy control group and are positively correlated with the severity of rosacea.

Botulinum toxin type A (BTX A) has gain widespread use in various neurological conditions, characterized by safe injection and less side-effect. This review will examine the current research of BTX A in the following aspects: mechanism, location, dose and outcome, which manifests the safety and efficacy data of BTX A injection treatment to the symptoms of Parkinson disease, including refractory tremor, focal dystonia, loss of postural reflexes, sialorrhea, gastrointestinal symptoms and depressive disorder.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin

Objective To discuss the feasibility and the curative effect of transurethral diverticulum section in the treatment of female urethral diverticulum.Method We retrospectively analyzed the transurethral diverticulum section surgeries of 11 adult female patients diagnosed as urethral diverticulum in our hospital from August 2012 to October 2016.The patients aged from 33 years old to 74 years old with an average age of 43.Their medical histories varied from 1 month to more than 40 years with an average histories of 80 months.Major symptoms included odynuria,frequent micturition,dyspareunia,perineum bearing-down feeling,repetitive urinary tract infection,dysuria,urinary stuttering,penis masses,etc.One patient underwent TVT-O.Two patients had urinary catheterization before the disease.During physical examination,cystic masses of different sizes could be touched on anterior vaginal walls with pain and secretion.Cystic lesions can be found by imaging examination.Transurethral diverticulum section was performed under general anesthesia.Using needle electrode by resectoscope,we made an annular incision in the direction of the vertical axis of the urethra,from the beginning of diverticulum ostium.The diverticulum completely communicated with the urethra.In 11 patients of transurethral endoscopic,the urethral sphincter and the diverticulum wall appeared morphological integrity and no damage.There was no liquid drained to de vagina.There was no urethral sphincter injury and no urethral vaginal leakage.We observed the operation time,bleeding volume,diverticulum position,the number of diverticulum,urethral sphincter intraoperative.We also observed the postoperative symptoms,short-term and long-term complications.Result All surgeries went on well,in which urethral diverticula were fully opened.The operation time was 30-45 minutes,average 35 minutes.The amount of bleeding within 5 ml.4 cases with multiple diverticulum,with 2 cases of diverticulum ostia were 2,2 cases of diverticulum ostia were 3.The other 7 cases with single diverticulum,diverticulum ostium was 1.The catheters were removed 2 weeks after the surgery,after that all patients can urinate normally.The follow-up time was 5-55 months (mean,24 months).All pre-surgical symptoms disappeared and no complication occurred,such as urethral stricture,urinary incontinence,urethro-vaginal fistula,etc.Conclusion Transurethral diverticulum section is a reliable treatment for female urethral diverticulum with positive curative effect and no obvious complication.

The main constituents of a typical medicinal herb,Polygonum muMflorum (Heshouwu in Chinese),that induces idiosyncratic liver injury remain unclear.Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats,whereas the solo treatment cannot induce observable injury.In the present work,using the constituent "knock-out" and "knock-in" strategy,we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats.Results indicated a significant elevation of plasma alanine aminotransferase,aspartate aminotransferase,and liver histologic changes,whereas other separated fractions failed to induce liver injury.The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats.Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract.Furthermore,the isolated cis-,and not its trans-isomer,displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats.Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples.In addition,plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats.All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu.Considering that the cis-trans isomerization of transSG was mediated by ultraviolet light or sunlight,our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

OBJECTIVE To study the effect of subchronic exposure to aluminum(Al)on learning, memory,and immediate early gene expression in rats,and to explore the toxic mechanism of Al on cognitive impairment of rats. METHODS Wistar offspring rats were administered with 2.0,4.0 and 8.0 g?L-1 AlCl3 in milk and drinking water in sequence from the postnatal day 1 to 3 months. Then,learning and memory of offspring rats were measured by Morris water maze, the hippocampal Al concentration was quantitated by the atomic absorption spectrophotometer, the CA1 area of the hippocampus was collected for HE observation, and the c-fos gene and c-Fos protein expression in CA1 area of the hippo?campus in offspring rats were detected by RT-PCR and immunohistochemistry. RESULTS Learning and memory of offspring rats in AlCl3 groups were significantly lower than those in control group(P<0.01,P<0.05). The hippocampal Al concentrations of offspring rats in AlCl3 groups were higher than those in control group(P<0.01). The morphology in CA1 area of offspring rats′ hippocampus in AlCl3 groups exhibited sparse nerve fibers, depigmentation and even vacuolar degeneration in neurons and other pathological changes after Al treatment;c-fos mRNA expression in the hippocampus in 4.0 and 8.0 g?L-1 AlCl3 group rats was significantly lower than in control and 2.0 g?L-1 AlCl3 group, respectively(P<0.01). c-Fos protein expression in offspring rats′ hippocampus in AlCl3 exposed groups was significantly lower compared with control group(P<0.01). CONCLUSION Al can injure learning and memory of rats,which is related to hippocampal neuronal dysfunction in CA1 area induced by pathological changes,low levels of c-fos gene and c-Fos protein expression subsequently.

Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside (THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration-dependent. Moreover, Fe3+ and Fe2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe and Fe2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde (molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2-O-glycoside (molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu2+, Ca2+, Zn2+, Mg2+ and Al3+. The product of THSG dimer with a water molecule was found in water containing Fe3+ and Fe2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap water should be taken by patients in a short time. Our investigation provides important information and reference about the influence of metal ions on the stability of decoctions in other traditional Chinese medicine that have unstable groups such as hydroxyls and unsaturated bonds, etc.

Objective To evaluate the effect of applying nursing cases in promoting accuracy of nursing grading . Methods A specialized-group of nursing cases was built to clear up the problems in nursing grading by using quality control system. The researchers surveyed the accuracy of nursing grading of 84 patients with activities of daily living ( ADL) score less than or equal to 60 ( ADL≤60) in two wards before and after the improvement project. The researchers compared the relative knowledge of nursing grading and sense of dynamically adapting nursing grading of 20 resident doctors, and self-ability of 7 nurses in specialized-group of nursing cases before and after the improvement project. Results The relative knowledge of nursing grading, ability of dynamically adapting classification and accuracy of classification were higher than before (χ2=42. 15, 8. 09,12.2;P<0. 01). The abilities of promoting nursing cases, communication, solving problem, reading literatures were significantly higher than before(t=-3.16,-4.90,-2.57,-4.90,-2.93;P<0.05). The dimension of responsibility had no significant difference ( t=-1.84,P=0.090) . Conclusions Nursing cases is effective in improving the accuracy of nursing grading, and promoting the ability and sense of improving nursing cases actively.