Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.

Objective:To learn about the epidemiological and clinical characteristics of children with brucellosis, in order to provide reference for clinical diagnosis and treatment of brucellosis in children.Methods:Clinical data of children with brucellosis (aged ≤14 years) who visited the Department of Infectious Diseases at Beidahuang Industry Group General Hospital from December 2020 to December 2022 were retrospectively collected, and their epidemiological characteristics, clinical characteristics, laboratory tests, treatment and outcome were summarized and analyzed.Results:A total of 34 children with brucellosis were included, including 25 males (73.53%) and 9 females (26.47%), with a gender ratio of 2.78 ∶ 1.00. The median age was 8 years and 1 month, mainly in the age group of 6 to 14 years (19 cases, 55.88%). Epidemiological investigation showed that most of the affected children were rural residents (25 cases, 73.53%), with more contact with cattle/sheep (26 cases, 76.47%). The onset time was mainly concentrated in summer (15 cases, 44.12%) and spring (13 cases, 38.24%). The clinical symptoms were mainly fever (97.06%, 33/34) and arthralgia (64.71%, 22/34). In the laboratory tests, 25 cases (73.53%) had positive blood cultures, and the white blood cell count (WBC) of 30 cases (88.24%) was (4 - 10) × 10 9/L. Among the abnormalities of liver function, aspartate aminotransferase (AST) increased in 19 cases (55.88%), alanine aminotransferase (ALT) increased in 14 cases (41.18%) and γ-glutamyl transpeptidase (GGT) increased in 6 cases (17.65%). Among the myocardial enzymatic abnormalities, α-hydroxybutyrate dehydrogenase (HBDH) increased in 29 cases (85.29%), lactate dehydrogenase (LDH) increased in 27 cases (79.41%), and creatine kinase isoenzyme (CK-MB) increased in 8 cases (23.53%). After treatment, 25 children with positive blood culture turned negative. Conclusions:Children with brucellosis are mainly male, older and rural residents. The clinical manifestations are mainly fever and arthralgia. Doctors in relevant departments should conduct detailed epidemiological investigations and laboratory tests for such children in clinical work, in order to achieve early detection, diagnosis and treatment of pediatric brucellosis.

Enteroviruses are currently divided into groups A to J, among which groups A to D can infect human body. People infected with enterovirus can present invisible infection, which can lead to different clinical symptoms when the immunity is weakened. Among the diseases caused by enteroviruses, hand-foot-mouth disease, herpetic angina, and encephalitis have attracted much attention. Coxsackie virus A21 (CV-A21) belongs to enterovirus C group, which mainly causes acute respiratory tract infection. According to research reports, CV-A21 infection has been found in many countries and regions, and the infection scope is gradually expanding. In the past two years, it has been found that CV-A21 infection has a significant association with the outbreak of acute respiratory tract infection. This indicates that acute respiratory tract infection caused by CV-A21 infection may have potential public health problems. However, there are few studies on the epidemiology and pathogenic mechanism of this virus, and most of the studies are on the mechanism of its oncolytic action on specific malignant tumors. Therefore, in this paper, the structural characteristics, epidemiological characteristics, infection mechanism and oncolytic effects of CV-A21 are reviewed to provide relevant clues for the understanding and exploration of CV-A21.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Objective:To analyze the clincial characteristics and laboratory findings of patients with neurobrucellosis (NB).Methods:Using retrospective analysis, clinical diagnosed patients with NB from June 2016 to February 2019 in Heilongjiang Agricultural Reclamation Bureau General Hospital were selected to analyze the general characteristics, clinical symptoms, laboratory examination results [white blood cell (WBC), hemoglobin(Hb), c-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), cerebrospinal fluid routine and biochemical, serum tube agglutination test (SAT), blood culture and cerebrospinal fluid culture of Brucella] , diagnosis and treatment effect. Results:A total of 25 patients were diagnosed with NB, including 19 males and 6 females, with an average age of (41.7 ± 14.2) years old, ranged from 11 to 70 years old. The main clinical symptoms were fever, headache, joint pain, vomiting and sweating, which accounted for 92.0% (23/25), 88.0% (22/25), 76.0% (19/25), 64.0% (16/25), and 64.0% (16/25), respectively. Positive neck ankylosis and mumbness of lowerlimbs were both 9 cases (36.0%), and mental disorders were 7 cases (28.0%). In 25 patients with NB, the WBC increased in 5 cases (20.0%), Hb decreased in 4 cases (16.0%), CRP increased in 13 cases (52.0%), ALT and AST both increased in 6 cases (24.0%), TP decreased in 21 cases (84.0%); SAT was positive in 25 cases (100.0%), cerebrospinal fluid SAT positive in 7 cases (28.0%); and blood culture was positive in 2 cases (8.0%). Cerebrospinal fluid changes were mainly manifested in 14 cases (56.0%) of chloride reduction, 13 cases (52.0%) of gluose reduction and 19 cases (76.0%) of protein increase. In 25 patients with NB, 17 cases were treated with doxycycline + rifampicin + ceftriaxone, 7 cases with etimicin + rifampicin + ceftriaxone, and 1 case with doxycycline + rifampicin + piperacillin sulbactam. After 6 to 12 months follow-up, 21 cases recovered well, whereas mild sequelae were observed in 4 patients.Conclusion:Clinical features of NB are hetorogeneous, and nerurological symptoms and cerebrospinal fluid examination are of great value in the diagnosis of NB.

Objective: To analyze the epidemiologic and clinical features of preschool children with brucellosis, and improve awareness of brucellosis and level of diagnosis. Methods: In-patients treated for brucellosis in preschool children from December 2016 to November 2018 in Heilongjiang Agricultural Reclamation Bureau General Hospital were retrospectively analyzed for epidemiology, clinical feature, laboratory data, treatment and prognosis. Results: There were 29 males and 16 females among the 45 preschool children brucellosis cases, with an average age of (3.7 ± 1.6) years old, ranged from 6 months to 6 years old. The patients of > 3-6 years old of age had the highest incidence (64.44%, 29/45). The patients were mainly rural residents (97.78%, 44/45). The onset time was mainly from March to June of the year (46.67%, 21/45). Clinical symptoms were mostly fever and joint pain, which accounted for 97.78% (44/45) and 57.78% (26/45), respectively. And lymph node enlargement and hepatosplenomegaly were also commonly seen, which accounted for 42.22% (19/45) and 35.56% (16/45). After treatment, the test results of patients with alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), α-hydroxybutyrate dehydrogenase (HBDH) and lactate dehydrogenase (LDH) were compared with those of before the treatment, the differences were statistically significant (t=4.774, 2.970, 2.229, 5.664, 5.805, P < 0.05). Before the treatment, 36 patients (80.00%, 36/45) had positive blood culture, which turned negative after the treatment. Conclusions The epidemiologic and clinical features of preschool children with brucellosis are not typical. In the epidemic area of the disease and multiple seasons, for children with unexplained fever, the clinician should inquire about the epidemiological history and combine the clinical feature, consider the possibility of brucellosis, and strive for early diagnosis and treatment.

Objective To analyze the epidemiology and clinical characteristics of Brucella infection in Heilongjiang Province,and to provide experience and basis for clinical treatment and prevention of brucellosis.Methods Using retrospective analysis method,clinically diagnosed patients with brucellosis from December 2016 to December 2017 in Heilongjiang Agricultural Reclamation Bureau General Hospital were selected to analysis the general characteristics,clinical symptoms,laboratory examination results,diagnosis and treatment effect.Healthy subjects undergoing health check-up at the same period were randomly selected as control group for laboratory blood biochemical test.Results A total of 396 patients were included in the brucellosis group,including 298 males and 98 females,with an average age of (43.6 + 15.6) years old,ranged from 1 to 75 years old.The control group included 125 cases,including 83 males and 42 females,with an average age of (41.7 ±+ 18.0) years old,ranged from 7 to 71 years old.There were no significant differences in age and gender between the two groups (t =1.083,x2 =3.789,P ＞ 0.05).The patients of ＞ 14-64 years old of age had the highest incidence (90.15％,357/396).The patients were mainly rural residents (76.01％,301/396) and the majority of them were farms (50.51％,200/396).The onset time was mainly from March to June of the year (47.73％,189/396).Clinical symptoms were fever,joint or muscle pain and hyperhidrosis,which accounted for 91.16％ (361/396),76.26％ (302/396) and 44.19％ (175/396),respectively.The levels of C-reactive protein (CRP),seropropane alanine aminotransferase (ALT),aspartate transaminase (AST),γ-glutamyl transpeptadase (γ-GT),alkaline phosphatase (ALP),α-hydroxybutyrate dehydrogenase (HBDH),and lactate dehydrogenase (LDH) in patients with brucellosis were significantly higher than those in the control group (t =4.956,2.746,4.019,3.272,7.008,3.728,3.409,P ＜ 0.01 or 0.05),while total protein (TP) and albumin (ALB) levels were reduced (t =-7.252,-8.601,P ＜ 0.01).After treatment,the test results of CRP,ALT,AST,γ-GT,TP,ALB,ALP,HBDH and LDH were compared with those before the treatment,and the differences were statistically significant (t =2.291,4.393,3.382,2.608,-7.516,-4.710,3.509,4.585,4.473,P ＜ 0.01 or 0.05).Conclusions The patients with brucellosis in Heilongjiang Province are mainly male farmers,and the onset time is mostly concentrated in March-June.The clinical manifestations of brucellosis are varied,clinicians should strengthen discrimination and prevent misdiagnosis.Medicines for brucellosis might be cautiously used in clinical trial,and changes in liver function and myocardial enzyme activity should be monitored.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Objective To investigate the differents of rapid enzyme-linked immunosorbent assay(IELISA) and the traditional serological methods in diagnosis of human brucellosis.Methods Brucella antibody was detected by IELISA,rose bangel plate test (RBPT),standard agglutination test (SAT),Coomb's test and cysteine test of serological methods in 430 confirmed and suspected patients and 300 healthy controls during the same period.The consistency was analyzed between IELISA and other tests.Results Positive rates of patients were significandy higher than those in healthy controls (IELISA:83.49％ vs.0;RBPT:86.97％ vs.0;SAT:76.27％ vs.0;Coomb's:65.58％ vs.0.02％;and cysteine test:67.91％ vs.0,x2 =535.05,412.47,437.66,339.22,489.49,all P ＜ 0.01).Positive consistency rates between IELISA and other tests were 87.19％,79.39％,71.59％ and 76.60％,the highest was between IELISA and RBPT,the lowest was between IELISA and Coomb's.Conclusions Brucella antibody is detected conveniently,quickly,and accurately by the joint application of RBPT and IEHSA,which provides important technical support for prevention and control of brucellosis.It is worthy of application extensively.

AIM:To examine the effects of thromboxane A 2 receptor ( TXA2 R) , the downstream product of cy-clooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS:The effects of TXA2 R antagonist SQ29548 and agonist U46619 on the proliferation of RA synovial cell line MH7A were detected by MTS cell proliferation assay , and their effects on COX-2 mRNA expression in MH7A cells were al-so examined by real-time PCR.In addition, the possible effect of U46619 on the proliferation of MH7A cells, when COX-2 was knocked down by siRNA , was determined by BrdU cell proliferation assay .RESULTS:SQ29548 inhibited the cell proliferation and the mRNA level of COX-2 while U46619 enhanced them.Moreover, U46619 reconstitute the proliferative ability of MH7A cells to some extent that inhibited by COX-2 siRNA.CONCLUSION: In RA synovial cells, TXA2R is able to control COX-2 expression, while it also mediates the effects of COX-2, suggesting that TXA2R might be an ideal candidate for RA treatment .