Objective To explore the mechanism of microRNA(miRNA)-365a-3p affecting the function of vascular endothelial cells involved in the pathogenesis of preeclampsia(PE).Methods Primary human umbilical vein endothelial cells(HUVECs)were set as a NC group(transfected miR-365a-3p NC),a mimics group(trans-fected miR-365a-3p mimics)and a inhibitor group(transfected miR-365a-3p inhibitor).Logarithmic HUVECs cells were set as the blank group.The cell proliferation,migration and angiogenesis in each group were detected.Dual luciferin assay verified the targeting relationship between miR-365a-3p and downstream gene.The protein expressions of TGF-β1,Smad4 and Smad7 in each group were detected.Results Compared with the blank group and the NC group,the absorbance value and mobility of 24,48 and 72 h were decreased(P＜0.05),the number of tubular structures per field were decreased in the mimics group(P＜0.05),the absorbance value and mobility of 24,48 and 72 h were increased(P＜0.05),and the number of tubular structures per field were increased in the inhibitor group(P＜0.05).Dual luciferin assay showed that Smad7 was a target gene of miR-365a-3p.Compared with the blank group and the NC group,the protein expressions of TGF-β1 and Smad4 in the mimics group were increased(P＜0.05),while the protein expression of Smad7 was decreased(P＜0.05).The protein expression levels of TGF-β1 and Smad4 in the inhibitor group were decreased(P＜0.05),while the protein expression levels of Smad7 were increased(P＜0.05).Conclusion miR-365a-3p may affect the function of vascular endothelial cells by regulating the downstream TGF-β signaling pathway,and thus participate in the pathogenesis of PE.

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

【Objective】 To analyze and master the serological and genetic characteristics of the samples with CisAB subtype and their genetic background. 【Methods】 From January 2018 to January 2022, blood samples with discrepant ABO blood typing results, from Zhengzhou voluntary blood donors and hospital patients, were subjected to phenotypic classification using micro column gel card and tube method, as well as amplification of exons 6 and 7 in ABO gene using PCR. The pedigrees of individuals with the same CisAB subtype but different serological typing results in the same family were analyzed. 【Results】 11 The forward typing of 12 samples was AB type, and unexpected antibodies against weaker antigens were found in 11 serum samples, including 9 cases with strong antigen A, 2 cases with strong antigen B, and 1 case with consistent forward and reverse typing results. Gene sequencing confirmed that 11 cases were CisAB01 subtype and 1 case was CisAB05 subtype.Among them, 7 cases had the genotype of CisAB01/O and serological phenotype of A2B3; 2 cases had the genotype of CisAB01/B and phenotype of A2B; 2 cases had the genotype of CisAB01/A and serological phenotype of A1Bx and A1B3; 1 case had the phenotype of AxB. In the CisAB01 family, 1 case of CisAB01/O with A2B3 phenotype and 1 case of CisAB01/B with A2B phenotype were detected. In the CisAB05 family, 2 CisAB05/O01 and 1 CisAB05/O02 were detected. 【Conclusion】 The serological phenotypes of different individuals in the same CisAB01 family can be different when paired with different ABO alleles. It is advisable to accurately identify the CisAB subtype genes with molecular biological methods to ensure blood transfusion safety.

Purpose: 5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy forpatients with advanced colorectal cancer, but many patients still suffer from treatment failuredue to 5-Fu resistance. Emerging observations revealed the important role of chemokine(C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosisin patients with colorectal cancer. This study is designed to reveal the important roleof CXCL-13 in causing colorectal cancer resistance to 5-Fu. Materials and Methods: CXCL-13 levels of patient's serum or cell culture supernatants were measured separatelyby enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell CountingKit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expressionin cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. Results: In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culturemedium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistantcells. Clinical studies showed that CXCL-13 is highly expressed in the serum of5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome.The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibodyovercame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced5-Fu resistance, which can be saved by added recombination CXCL-13. Conclusion These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but alsoprovide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatmentstrategies.

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth. At about the age of 2 years, sparse hairs of non-uniform thickness began to grow, but they fell out intermittently and were broken easily. Some eyebrows and eyelashes of different lengths fell out or were broken. Physical examination revealed good condition of nutrition, normal height, weight and intelligence, with no obvious abnormalities in other systems. Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput. Teeth, nails, toenails and sweat glands were normal. Dermoscopy, optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance. Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene, and a heterozygous mutation c.574T>C (p.S192p) (NM-177986) in the DSG4 gene, which were inherited from her father and mother respectively. None of the above mutations in the DSG4 gene were found in 100 healthy controls. According to the gene sequencing results and clinical phenotype, the patient was finally diagnosed with autosomal recessive hereditary monilethrix, and the c.574T>C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Objective To explore the clinical characteristics and risk factors of occult pneumonia in advanced elderly patients.Methods A total of 170 advanced elderly patients with community-acquired pulmonary infection in geriatric department of Xijing hospital from January 2014 to October 2017 were enrolled.Patients were divided into two groups:the observation group (with occult pneumonia,n=80)and the control group(without occult pneumonia,n =90).Clinical data of patients were collected,and clinical characteristics and related risk factors of occult pneumonia in elderly patients were analyzed.Results There was no statistically significant difference in the positive rate of sputum culture and the distribution of pathogenic bacteria between the two groups (P ＞ 0.05).Gram-negative bacteria predominated in pathogenic bacteria.The hospitalization time was longer in the observation group than in the control group[(17.3 ± 3.0) d vs.(10.3 ± 3.9) d,P ＜ 0.05].The mortality rate was higher in the observation group than in the control group(10.0 ％ vs.3.3 ％,P ＜ 0.05).The age was older in the observation group than in the control group[(87.0± 1.7) years vs.(82.0± 2.4) years,P ＜ 0.05].The incidences of diabetes,Alzheimer's disease,hypothyroidism and long-term bed rest were higher in the observation group than in the control group (P ＜ 0.05).Multivariate logistic regression analysis showed that age (OR =6.93),dementia (OR =4.32),hypothyroidism(OR =4.89) were independent risk factors for occult pneumonia (P ＜ 0.05).Conclusions The pathogenic bacteria in advanced elderly patients with occult pneumonia are mainly gram-negative bacteria.The positive rate of CT scan confirmed-occult pneumonia is much higher than that by chest X-ray.The advanced elderly patients with occult pneumonia have longer hospitalization time and higher mortality rates.Old age,senile dementia and hypothyroidism are independent risk factors for occult pneumonia in advanced elderly patients.

One hundred and forty-five patients with primary aldosteronism (PA) admitted from 2006 to 2013 were enrolled in the study. The diagnosis of PA was confirmed by upright furosemide test and all patients met the following criteria: ① round-or oval-shaped lesion of low density with diameter>1 cm in one adrenal gland shown in contrast CT scan; ② no lesion or abnormality in contralateral adrenal gland; ③serum potassium level<3.5 mmol/L. Of 145 patients, 106 underwent total adrenalectomy, 36 partial adrenalectomy and 3 tumor enucleation. Serum potassium was (2.75±0.55) mmol/L before and (4.03±0.46) after surgery. Potassium was normalized after treatment in 141 cases (97.2％) with correction or improvement in hypertension; 4 patients (2.8％) remained hypokalemic and received spironolactone. Patients with normalized potassium were followed up for a medium period of 74 months (22—103 months), of whom 32 (22.7％) dropped off; the remaining 109 (77.3％) patients did not have hypokalemia. Multivariate linear correlation analysis showed that serum potassium level was negatively correlated with tumor diameter (r=?0.273,95％ CI:?0.086—?0.564, P=0.026) and basal serum aldosterone level (r=?0.261,95％ CI:?0.047— ?0.514, P=0.036). In PA patients with unilateral adrenal macroadenoma and hypokalemia, satisfactory surgical resolution can be achieved without adrenal venous sampling in majority of patients.

Objective To find out the epidemic characteristics of brucellosis in Harbin and provide scientific evidences for development of countermeasures.Methods The brucellosis surveillance data were collected from the "National Diseases Surveillance Information Management System" and the municipal surveillance results from 2013 to 2017 in Harbin;the place,time and population distribution characteristics of brucellosis were analyzed by descriptive epidemiological methods.Results A total of 2 909 cases of brucellosis were reported in Harbin from 2013 to 2017,and the incidence of brucellosis declined from 5.98 per 100 000 to 4.53 per 100 000,the epidemic situation was mainly sporadic,and an outbreak caused by a live Brucella vaccine (A19 strain) was reported in 2017;all eighteen districts (counties or cities) in Harbin had reported epidemic in the past five years,Shuangcheng,Yilan,Binxian and Bayan had a large number of cases,accounted for 53.76％ (1 564/2 909) of the total number of patients in Harbin;the time of onset focused on March to July,which accounted for 57.17％ (1 663/2 909) of annual incidence;age distribution,mainly young adults aged 30 to 59,accounted for 72.57％ (2 111/2 909);gender distribution predominandy male,accounted for 75.42％ (2 194/2 909);and occupational distribution predominantly farmers,accounted for 86.28％ (2 510/2 909).In the municipal surveillance stations from 2013 to 2017,7 005 cases were surveyed,of which 2 141 cases received serological test,the positive rate was 3.32％ (71/2 141),except 2016,the serum positive rate was decreasing year by year (x2 =13.927,P ＜ 0.05),and the monitoring results of municipal monitoring stations can better reflect the epidemic trend.Conclusions The incidence of brucellosis in Harbin is decreasing year by year.However,the outbreak caused by the new vaccines should be given high attention and we should strengthen prevention and control of the disease.

A 22-year-old male patient visited the Department of Dermatology of the First Affiliated I Iospital of Zbengzhou University on October 31,2016 due to dark red papules,nodules,pustules and cysts on the face,neck,back and in the axillary and inguinal regions for 6 years,and multiple dark purple plaques and ulcers on bilateral lower limbs for 1 year.Six years ago,the patient was diagnosed with acne in other hospital,and no treatment was given.One year ago,multiple purple plaques occurred on the bilateral lower limbs,which then ruptured and progressed into ulcers with diameters of 1-12 cm.On May 9,2002,the patient visited the Department of Pediatric Medicine of the First Affiliated Hospital of Zhengzhou University due to the left knee joint swelling and pain for half a year.Laboratory examination showed negative rheumatoid factor,and smear examination of the left knee joint effusions revealed that there were neutrophils and a small amount of lymphocytes and monocytes in the joint effusions,and no abnormal cells were observed.Then,the patient was diagnosed with pyogenic arthritis of the left knee.Physical examination at admission showed poor general condition,walking difficulty,slightly increased blood pressure of 142/92 mmHg (1 mmHg =0.133 kPa),multiple purple plaques on the bilateral lower limbs with central ulcer formation.Histopathological examination of ulcer margin on the lower limbs showed ulceration,intercellular edema and infiltrating neutrophils in the epidermis,and edema,focal erythrocyte extravasation,diffuse infiltration of neutrophils,lymphocytes and histiocytes in the superficial and middle dermis.Clinical manifestations and pathological features confirmed a diagnosis of pyoderma gangrenosum.There were extensive inflammatory papules,pustules,abscesses and cysts on the face,neck,waist and back,and a small amount of dark red nodules on the axillary and inguinal regions,which were consistent with cystic acne and hidradenitis suppurativa.As PSTPIP1 gene sequencing showed,no mutations were found in exon fragments,while compound heterozygous mutations c.36 + 68 G ＞ A,c.137 + 47 G ＞ C and c.562 + 114 C ＞ G her were found in intron fragments.Among 100 healthy controls,45 carried the same mutations.So,these mutation sites were considered to be polymorphic sites,and the pathogenicity of these mutations was still unclear.Finally,the patient was diagnosed with PAPASH syndrome.The patient was treated with methylprednisolone,cefminox,isotretinoin and thalidomide,and the lesions were markedly improved after 2 weeks.Now the patient was still followed up.

Objective    To investigate how to establish stable mice cervical heart transplantation model. Methods    Totally, 40 male C57 mice with the age of 6-8 weeks and weight of 19-24 g were randomly divided into recipients and donors (n=20 in each group). Mice cervical heart transplantation model was established by connecting the ascending aorta of donors to the right cervical common artery of recipients through end to side anastmosis and the pulmonary artery of donors to the right external jugular vein of recipients through end to end anastmosis. Results    More than 95% recipients survived after surgery. Cold ischemia time was 15±5 min, warm ischemia time 23±6 min, and the whole operation took about 55±15 min. The recipients survived more than 30 d with functional heart grafts. Histologically, there was no difference between the heart graft one month after the transplantion and the normal heart. Conclusion    Cervical heart transplantation of mice model is reliable and feasible, which is easy to monitor the survival condition of heart graft by visual examination and palpation, which will benefit the basic research in transplantation field.