ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan， excavate and analyze the key information of Xieqingwan， and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition， dosage， decocting methods， usage， and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows： Angelicae Sinensis Radix， Gentianae Radix et Rhizoma， Chuanxiong Rhizoma， Gardenia seeds， Radix et Rhizoma Rhei， Notopterygii Rhizoma et Radix， and Saposhnikoviae Radix were grounded to fine powder， decocted with honey， and finally formed into pills with the size of a chicken head （1.5 g）. It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology， neurology， dermatology， digestion， and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity， removing fire and relaxing the bowels， and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan， which is often modified and used in treating Tourette syndrome， herpes， febrile convulsion， sleepwalking， and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan， induces its historic evolution， and confirms its key information， so as to provide a reference for the future development of Xieqingwan.

Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.

Background:Intestinal microbiota dysbiosis and impaired intestinal barrier,leading to bacterial translocation,are involved in acute pancreatitis(AP)exacerbation.Antimicrobial peptides participate in the regulation of intestinal microbiota,yet their changes and roles in the course of AP are unclear.Aims:To investigate the dynamic changes and significance of antimicrobial peptides in the ileum and pancreas among three classical AP models.Methods:Three AP mouse models were established by using cathelicidin plus lipopolysaccharide(CAE+LPS),sodium taurocholate(N-Tau)and L-arginine(L-Arg),respectively.The pathological changes of pancreatic and ileal tissues were observed and scored.Real-time PCR was applied to detect the expression levels of the proinflammatory cytokines,and antimicrobial peptides including lysozyme(LZM),secretory phospholipase A2(sPLA2),angiogenin 4(Ang4),regenerating islet-derived protein 3(REG3)family,β-defensin family,cathelicidin-related antimicrobial peptide(CRAMP),and glycoprotein 2(GP2)in ileum and/or pancreas.The association between expressions of antimicrobial peptides and the injuries of pancreas and ileum was analyzed.Results:Pancreatic and ileal injuries could be observed in all three AP models in different time points with various degrees.The pathological scores of the CAE+LPS and N-Tau models reached the highest level and then declined from 0-72 h,while those of L-Arg model progressively increased within 72 hours.Compared with the corresponding controls,the mRNA levels of LZM,sPLA2,and Ang4 in ileal tissue,and the mRNA levels of CRAMP,GP2,and β-defensins in pancreatic tissue,were generally downregulated in all three AP models(all P<0.05).CAE+LPS and N-Tau models showed a trend of initial decrease followed by partial recovery,while L-Arg model exhibited a gradual downregulation trend.The mRNA levels of REG3β and REG3γ in ileum upregulated and reached the peak at 48 h or 24 h and downregulated significantly at 72 h in all three AP models(all P<0.05);while in pancreatic tissue,both REG3β and REG3γ were generally upregulated in all three AP models(all P<0.05),but fell back in CAE+LPS and N-Tau models at 72 h.The mRNA levels of ileal β-defensins upregulated significantly in the early stage of the disease(12 h)in all three AP models(all P<0.05),and then gradually decreased.Spearman correlation coefficient analysis showed that the expressions of ileal LZM,sPLA2,and Ang4,as well as the pancreatic CRAMP,GP2,and β-defensins,were significantly negatively correlated with the pancreatic and ileal pathological scores in all three AP models(all P<0.05);but the expression of REG3β in the pancreas was significantly positively correlated with the pancreatic and ileal pathological scores(all P<0.05).Conclusions:The expressions of LZM,sPLA2,and Ang4 in the ileum,as well as the expressions of CRAMP,GP2,β-defensin family,and REG3β in the pancreas of the three classical AP models,dynamically changed with the severity of the disease.Ileal and pancreatic antimicrobial peptides may affect the injuries of pancreas and intestine during AP by regulating intestinal microbiota.

ObjectiveTo explore the therapeutic mechanism of Faeces Bombycis on diabetic gastroparesis （DGP） rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein （PI3K/Akt/mTOR） signaling pathway. MethodDGP rat model was prepared by random selection of 15 out of 105 rats as blank group. The rats successfully constructed were randomly divided into model group， high-，medium- and low- dose groups （3.2， 1.6， 0.8 g·kg^-1） and moxapride group （1.5 mg·kg^-1）， with 12 rats in each group， and were given gavage for 4 weeks. The gastric emptying rate and random blood glucose were measured. The morphological changes of gastric antrum were observed by hematoxylin-eosin （HE） staining， and the expression of the c-Kit gene was analyzed by immunohistochemistry. The apoptosis of Cajal interstitial cells was observed by in situ end labeling （TUNEL） staining， and the protein expressions of PI3K， phosphorylation（p）-PI3K， Akt， p-Akt， mTOR， and p-mTOR were detected by Western blot. ResultCompared with the blank group， the gastric emptying rate of the model group decreased significantly （P<0.01）， and the glandular structure of the gastric antrum was destroyed. The expression of c-Kit decreased （P<0.01）， and the apoptosis of Cajal interstitial cells （ICC） increased. Compared with the model group， the gastric emptying rate in the high， middle， and low-dose groups of Faeces Bombycis extract and mosapride group increased significantly （P<0.01）. The glandular structure of the gastric antrum became closer， and the apoptosis of ICC decreased. The expression of c-Kit in the high dose group of Faeces Bombycis extract increased significantly. After Western blot testing， compared with the blank group， the protein expression of p-Akt/Akt， p-PI3K/PI3K， and p-mTOR/mTOR in the model group increased. Compared with the model group， the protein expression of p-Akt/Akt in the high dose group of Faeces Bombycis extract decreased （P<0.01）， and the protein expression of p-PI3K/PI3K decreased in the middle and low dose groups of Faeces Bombycis extract and mosapride group decreased （P<0.05， P<0.01）. The protein expression of p-mTOR/mTOR decreased in the low dose group of Faeces Bombycis extract （P<0.05）. In terms of random blood glucose， compared with the blank group， the random blood glucose in the model group increased significantly （P<0.01）， and compared with the model group， the random blood glucose in the high and middle dose groups of Faeces Bombycis extract decreased significantly （P<0.05）. Compared with mosapride group， the protein expression of p-Akt/Akt decreased in the high dose group of Faeces Bombycis extract （P<0.05）， and the protein expression of p-PI3K/PI3K increased in the high， middle， and low dose groups of Faeces Bombycis extract （P<0.05， P<0.01）. ConclusionFaeces Bombycis extract can increase gastric emptying rate， reduce ICC apoptosis， and lower random blood glucose in DGP rats. The high dose group of Faeces Bombycis extract has a significant effect on inhibiting ICC apoptosis， and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

BACKGROUND:Low to moderate intensity aerobic exercise can help protect knee cartilage.Long-chain non-coding RNAs are crucial for gene regulation.Among them,HOTAIR can activate numerous transcriptional co-repressors to repress the activation of certain genes. OBJECTIVE:To detect the expression levels of HOX transcript antisense RNA(HOTAIR)and other related factors in chondrocytes of high fat-fed mice and after low to moderate intensity exercise intervention,and to investigate their role in cartilage injury and sports rehabilitation. METHODS:Thirty C57BL/6 male mice were randomly divided into control group(normal feeding),high fat feeding group and high fat feeding plus treadmill exercise group,with 10 mice in each group.The mice in the high fat feeding plus treadmill exercise group were subjected to an 8-week low to middle intensity treadmill exercise,and the mice in the other two groups were caged.During this period,body mass was weighed every week on Sunday.After the 8-week exercise,both lower extremities of mice were taken,and the knee joint was scanned using Micro CT to make a 3D femoral condyle image to obtain relevant parameters.Hematoxylin-eosin and safranin O-fast green staining of the knee joint were performed for Mankin and Osteoarthritis Research Society International(OARSI)scoring.RT-PCR was performed to detect the mRNA levels of cartilage metabolic indicators and lipid metabolism indicators,including type II collagen,matrix metalloproteinase 13,interleukin 1,low-density lipoprotein receptor-related protein 5,HOTAIR and its downstream factor lysine specific demethylase 1. RESULTS AND CONCLUSION:The body mass of high fat-fed mice were higher than that of the control group(P<0.01),and the body mass of the high fat feeding plus treadmill exercise group was lower than that of the high fat feeding group(P<0.05).The connectivity density of high fat-fed mice was higher than that of the control group(P<0.01).Mankin and OARSI scores of the high fat feeding were higher than those of the control group(P<0.01)and high fat feeding plus treadmill exercise group(P<0.05).The mRNA level of type II collagen was higher in the control group than the high fat feeding plus treadmill exercise group(P<0.05)and high fat feeding group(P<0.01)as well as higher in the high fat feeding plus treadmill exercise group than the high fat feeding group(P<0.01).The mRNA levels of matrix metalloproteinase 13,interleukin 1,low-density lipoprotein receptor-related protein 5,HOTAIR and lysine specific demethylase 1 were higher in the high fat feed group than the control group and high fat feeding plus treadmill exercise group(P<0.01).To conclude,high fat feeding can increase the bone substance of the femoral condyle,lead to knee cartilage wear,and cause chondrocyte metabolism disorder.HOTAIR is highly expressed in this process.An 8-week low to middle intensity treadmill exercise can reduce body mass,alleviate knee cartilage wear,improve chondrocyte function and down-regulate HOTAIR expression in mice.

Objective:To retrospectively analyze a pediatric case of X-linked hypophosphatemic rickets treated with Burosumab and improve clinicians′ awareness of the safety and effectiveness of the drug.Methods:Clinical data of the child were collected. Whole-exon genetic testing after parental consent confirmed X-linked hypophosphatemic rickets. During 18 months of Burosumab treatment, fasting blood phosphorus, alkaline phosphate, calcium, and calcium phosphate product were monitored every 11-14 days. Parathyroid hormone and 25 hydroxyvitamin D were checked every 2-6 weeks, while knee spacing, liver and kidney function, urinary calcium creatinine ratio, electrocardiogram were assessed every 3 months. Radiological imaging was performed every 6 months, with continuous follow-up of the child.Results:Whole-exon sequencing results showed a c. 1080_1081insCAATGTTA(p.T361Qfs*3) spontaneous heterozygous frameshift mutation in the PHEX gene in the child, which has not been reported previously. After the patient was treated with Burosumab for 18 months, the biochemical indexes were significantly improved, and the rickets score was reduced, without gingival abscess or other adverse events.Conclusion:The variant c. 1080_1081insCAATGTTA(p.T361Qfs*3) in the PHEX gene was identified as the cause of the patient′s condition. Burosumab, as a targeted therapeutic agent for X-linked hypophosphatemic rickets, showed significant treatment efficacy.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.