Objective: To investigate the potential of conventional cranial computed tomography (CT) in assessing the early neurological deterioration(END), long-term prognosis, and traditional Chinese medicine (TCM) syndrome elements during the acute phase in patients with acute ischemic stroke (AIS). Methods: This study included 101 patients with AIS onset within 24 h in the Emergency Department of Fangshan Hospital, Beijing University of Chinese Medicine, from November 2019 to May 2021. To investigate the correlation between the relevant characteristics of the first conventional cranial CT in patients with AIS onset within 24 h and END, 90 d prognosis, and initial syndrome elements, the presence or absence of END, the 90 d prognosis (non-disabling outcome or functionally independent outcome), and the establishment of syndrome elements (internal fire, phlegm-dampness, blood stasis, qi deficiency, yin deficiency) were used as dependent variables and grouping criteria. Results: This study included 61 males and 40 females, with an age of (64.43±10.56) years. The time from onset to conventional cranial CT examination was 3.50 (1.50, 9.75) h. Among the patients, there were 70 cases (69.3%) of mild AIS, 30 cases (29.7%) of moderate AIS, and one case (1.0%) of severe AIS. Fifteen patients (14.9%) received intravenous thrombolysis. Among the 101 patients, six syndrome elements were observed within 24 h of onset: internal wind in 101 cases (100.0%), internal fire in 58 cases (57.4%), phlegm-dampness in 60 cases (59.4%), blood stasis in 67 cases (66.3%), qi deficiency in 39 cases (38.6%), and yin deficiency in 23 cases (22.8%). The incidence of END was higher in patients with lesions in the contralateral cerebral hemisphere to the affected limb (32.9%) than in those without such lesions (10.7%), showing a strong positive correlation with END occurrence (OR=4.082, P = 0.026). The incidence of END was higher in patients with lesions in the basal ganglia region (33.3%) and the carotid system blood supply area (32.8%) than in those without lesions in the basal ganglia region (15.8%) and the carotid system territory (14.7%), showing moderate positive correlations with END occurrence (OR=2.667, P =0.047; OR=2.836, P=0.044). The proportion of non-disabling outcomes was lower among patients with white matter degeneration (30.8%) and lesions in the contralateral cerebral hemisphere to the affected limb (52.1%) than in those without white matter degeneration (63.6%) and without such lesions in the contralateral cerebral hemisphere to the affected limb (78.6%), both showing strong negative correlations with the occurrence of non-disabling outcomes (OR=0.254, P=0.034; OR=0.296, P=0.015). Similarly, the proportion of functionally independent outcomes was lower among individuals with white matter degeneration (30.8%) and lesions in the contralateral cerebral hemisphere to the affected limb (64.4%) than in those without white matter degeneration (77.3%) and without such lesions in the contralateral cerebral hemisphere to the affected limb (89.3%), both also showing strong negative correlations with the occurrence of functionally independent outcomes (OR=0.131, P=0.001; OR=0.217, P=0.014). The incidence rates of internal fire, blood stasis, and yin deficiency syndrome elements were 66.7%, 73.0%, and 30.2%, respectively, among patients with lesions in the basal ganglia region, compared to 42.1%, 55.3%, and 10.5% among those without lesions in this region. The presence of lesions in the basal ganglia region showed moderate to strong positive correlations with internal fire and yin deficiency syndrome elements (OR=2.750, P=0.016; OR=3.670, P=0.028). Patients with lesions in the centrum semiovale and corona radiata regions (66.7%) had a higher incidence of qi deficiency than those without lesions in this region (33.7%), showing a strong positive correlation with the occurrence of qi deficiency (OR=3.931, P=0.022). No CT characteristics were found to be correlated with phlegm-dampness syndrome elements. Conclusion The first cranial CT in patients with AIS has potential application value in predicting disease progression, assessing prognosis, and diagnosing syndromes, which can provide physicians with diagnostic and treatment decisions to improve the long-term prognosis of patients with AIS.

Objective:To analyze the mutation characteristics of rpoB gene in rifampicin-resistant Brucella strains. Methods:DNA of 4 rifampicin-resistant Brucella strains (JSY-26, G-9, WSY-13 and AW-3) isolated from Xinjiang Uygur Autonomous Region was selected, rifampicin rpoB gene was amplified by PCR and its nucleotide sequence was sequenced. The rpoB gene sequences of rifampicin-resistant Brucella standard strain (RB51) and sensitive strain (ALT-8) were used as reference, the mutation sites and types of the rpoB gene inside and outside the rifampicin resistance determination region (RRDR) of the 4 rifampicin-resistant Brucella strains were analyzed by Mega 7.0 software. Results:Through sequence alignment, both JSY-26 and WSY-13 strains underwent a single base point mutation at the RRDR 1 576 bp of the rpoB gene, with the base changing from guanine (G) to adenine (A). The G-9 strain underwent a single base point mutation at the RRDR 1 606 bp of the rpoB gene, with the base changing from cytosine (C) to A. The AW-3 strain showed 5 mutations of 3 types outside rpoB gene RRDR at 2 536, 2 537, 2 626, 2 636 and 2 654 bp, namely 3 insertion mutations [thymine (T) insertion once and C insertion twice], 1 deletion mutation (C deletion), and 1 single base point mutation (from G to C mutation).Conclusion:The RRDR mutations in the rpoB gene of the rifampicin-resistant Brucella strains are mainly characterized by single base point mutations, while multiple insertion and deletion mutations occur outside the RRDR.

Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and stem cell regeneration. Dysregulation of this pathway has been linked to various diseases, such as cancer, heart disease, lung disease, kidney disease, liver disease, and immune dysfunction, as well as ocular diseases. Consequently, regulating the balance of Hippo signaling pathway may be an effective treatment for ocular diseases. This article reviews the mechanism of action and therapeutic potential of Hippo signaling pathway in ocular diseases, and discusses the potential therapeutic targets of the Hippo signaling pathway, to identify new targets and provide new research ideas for treating ocular diseases.

OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Metabolic diseases refer to metabolic disorders caused by abnormal material metabolism or energy metabolism of the body such as diabetes,hyperlipidemia,hyperuricemia and liver disease.In recent years,with the change of national diet structure,its incidence has increased year by year,which seriously endangers national physical and mental health.In modern medicine,long-term treatment of metabolic diseases is often used in the treatment of chemical drugs,which is easy to produce drug resistance and liver and kidney damage.Tannin is a class of polyphenolic compounds composed of glucose,gallic acid,flavanols,etc.,which has antibacterial,anti-tumor,anti-oxidation,hypoglycemic,antiviral,anti-inflammatory and analgesic effects,and has a clear easing effect on metabolic diseases.Tannin in the treatment of metabolic diseases has the advantages of less toxic side effects,significant curative effect,low cost,easy to popularize,etc.,which provides a better choice for the treatment of metabolic diseases.

Objective : To investigate the trends in incidence of malignant tumors in Yongkang City, Zhejiang Province from 2013 to 2019, so as to provide insights into formulation of the malignant tumor control strategy. Methods: Data pertaining to the incidence of malignant tumors from 2013 to 2019 were captured from the Zhejiang Chronic Disease Monitoring Information System. Based on the International Classification of Diseases 10th Revision (ICD-10) and data from the national population census, the constituent ratio, crude incidence and Chinese population-standardized incidence of malignant tumors were estimated, and the trends in incidence of malignant tumors were investigated using annual percent change (APC). Results: The annual mean crude incidence and Chinese population-standardized incidence of malignant tumors were 356.75/105 and 226.97/105, which both appeared an overall tendency towards a rise (APC=5.887% and 4.815%, both P<0.05). The crude incidence of malignant tumors appeared a tendency towards a rise among both men (APC=3.860%, P<0.05) and women (APC=8.534%, P<0.05) from 2013 to 2019, and the Chinese population-standardized incidence of malignant tumors appeared a tendency towards a rise among women (APC=8.392%, P<0.05). The largest increase in the crude incidence of malignant tumors was seen among women at ages of 15 to 44 years (APC=11.599%, P<0.05). In addition, the Chinese population-standardized incidence of lung cancer, colorectal cancer and thyroid cancer all showed a tendency towards a rise among men (all P<0.05), and the Chinese population-standardized incidence of lung cancer and thyroid cancer both appeared a tendency towards a rise among women (both P<0.05). Conclusions The incidence of malignant tumors showed a tendency towards a rise in Yongkang City from 2013 to 2019, and the elderly and young females are high-risk populations for malignant tumors. Lung cancer, thyroid cancer and colorectal cancer are cancers that should be given a high priority.

ObjectiveTo establish a set of single nucleotide polymorphisms (SNP) detection protocol for inbred rats based on multiplex PCR-ligase detection reaction (LDR). MethodsA total of 40 rats SNP sites were selected on chromosomes 1-20 and X of rats among 5 inbred strains of rats, and the 40 SNP sites were randomly divided into four groups. A genetic detection protocol for 4 groups of SNP in inbred rats based on multiplex PCR-LDR technology was constructed. 9 commonly used rat strains from two other domestic rat suppliers were detected by this protocol. Finally, the feasibility of this protocol was verified by comparing the amplification effects of different DNA polymerases by a third-party laboratory. ResultsWhen using the constructed SNP detection protocol for inbred rats to test 5 rat strains, all sites in each sample obtained good amplification results. The 9 commonly used rat strains from two other rat suppliers in china were also well amplified by this SNP detection protocol, and 40 SNPs were homozygous in each Inbred strain. The results of detection of the same rat DNA samples with three different DNA polymerases showed that the Multiplex PCR Kit, AmpliTaq Gold 360 DNA polymerase and Platinum II Taq hot start DNA polymerase had electrophoretic peaks of amplification products at all SNP sites in groups 1 to 3, and Platinum II Taq hot start DNA polymerase had one less electrophoretic peak of the amplification products at the SNP sites in group 4. In addition, inter-laboratory comparisons showed consistent results for the same amplification system. ConclusionBased on multiplex PCR-LDR technology, this study successfully established a SNP detection protocol for rats covering all autosomes and X chromosomes with the excellent stability and repeatability.

The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses seri-ous threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates col-lected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009-2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host-blaKPC-carrying plasmid(Clade 3.1+3.2-IncFⅡpHN7A8,Clade 3.1+3.2-IncFⅡpHN7A8:IncR,and Clade 3.3-IncFⅡpHN7A8:InCpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advanta-geous combinations might be directly associated with the strong population expansion during 2007-2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP-plasmid combinations.

Objective:To investigate the risk factors of acute pancreatitis (AP) complicated with thrombotic diseases.Methods:Clinical data of 5 223 patients with AP admitted to the General Hospital of Ningxia Medical University from January 2015 to September 2020 were retrospectively analyzed. They were divided into thrombosis group and non-thrombosis group according to whether they were complicated with thrombotic diseases. The following data were recorded: gender, age, past history, time of onset, etiology, severity grade of AP, BISAP score, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer(D-D), fibrinogen(FIB), white blood cell count(WBC), platelet count (PLT), lactate dehydrogenase (LDH), blood glucose level, with or without hypoalbuminemia, hypertriglyceridemia and hypercholesterolemia, date of diagnosis, location of thrombus, clinical manifestations and anticoagulant therapy. Univariate and Logistic multivariate regression analysis were used to analyze the risk factors of AP complicated with thrombotic diseases. The receiver operating characteristic (ROC) curve was drawn, the area under the curve (AUC) was calculated, and the efficacy of independent risk factors in predicting AP complicated with thrombotic diseases was evaluated.Results:46(0.88%) of 5 223 patients with AP were complicated with thrombosis, which occurred 8.50(2.00-15.00) days after the onset of AP; the age of onset was 66 (52-74) years; the patients with thrombotic diseases were mostly SAP patients (23/46, 50%); the most common type was deep venous thrombosis in lower extremity (19/46, 41.3%); 37 patients (80.4%) received regular anticoagulant treatment after finding thrombus, and no bleeding was found during hospitalization. Univariate analysis showed that the age of patients with thrombosis was higher than that of patients without thrombosis, APTT value was prolonged, D-D value was increased, WBC was decreased and SAP was more in AP severity, the number of patients with BISAP score ≥3 was increased significantly, and the differences were statistically significant ( P<0.05). Multivariate logistic regression analysis showed that AP severity ( OR=3.017, 95% CI 1.799-5.061, P<0.001) and age ( OR=1.029, 95% CI 1.000-1.059, P=0.049) were independent risk factors for AP patients complicated with thrombosis. The AUC of AP severity and age in predicting AP complicated with thrombotic diseases were 0.714 and 0.625, respectively. The sensitivity was 67.4% and 47.8%, and the specificity was 70.6% and 77.9%, respectively. Conclusions:The severity grade and age of AP were independent risk factors for AP complicated with thrombotic diseases. Early vigilance and clinical intervention should be given.

Objective:To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2).Methods:The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children′s Hospital in April 2019 were reported. A literature search with "Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Relevant published articles were reviewed.Results:The two cases presented with chronic and severe hyponatremia with hypo-osmolality, inappropriately elevated urinary osmolality and urinary sodium levels. The onset age was 5.25-years and 2 months respectively. AVPR2 sequencing revealed a previously described hemizygous activating mutation (c.409C>T, p.R137C) in both of boys, each inherited the variant from their mother. Patient 1 limited fluid intake by himself in his daily life, intravenous and oral sodium supplementations showed no significant increase of serum sodium level. Oral furosemide increased the serum sodium level and maintained it within normal range. The serum sodium and potassium levels were in the normal range during the 1-year follow-up period with oral furosemide. The serum sodium level of Patient 2 increased with restricting fluid intake and with salt supplementation. However, after he experienced respiratory infection, the plasma sodium level decreased. Subsequently, oral anti-infection medicine and furosemide were applied. The serum sodium level increased two days later and remained at a normal range afterwards. The boy was 1 year old with normal growth. He stopped taking furosemide after 4 months while taking 1 gram of salt per day, the blood sodium level maintained at normal range. Literature search identified no reports in Chinese journals, whereas 50 publications were found in English journals. A total of 30 NSIAD probands were reported and 16 of those (53%) had childhood onset, most presented with seizures. The majority had a hotspot change at the nucleotide position of 409 in AVPR2. Nine cases had an amino acid change as R137C and five cases as R137L. Fluid restriction and oral urea intake were main treatment options, no report so far was found with oral furosemide treatment.Conclusions:NSIAD presented with hyponatremia without any other specific presentations. Genetic testing for variants in AVPR2 is helpful for early diagnosis and timely treatment. The first two cases of oral furosemide treatment were reported by the article which helped to maintain a normal serum sodium level after limiting fluid intake and supplementing sodium which showed limited effect.