Malignant tumors， with the increasing crude morbidity and mortality year by year， have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions， which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth， improve the quality of life of patients， and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years， they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis， inhibition of tumor cell migration and invasion， suppression of proliferation， induction of autophagy of tumor cells， cell cycle arrest， inhibition of tumor angiogenesis， regulation of microRNA， and modulation of immunity. In addition， Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， c-Jun N-terminal kinase （JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， mammalian target of rapamycin （mTOR）， Notch， Hedgehog， Wnt/β-catenin， and other signaling pathways to participate in the processes of tumor proliferation， invasion and metastasis， autophagy and apoptosis， and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility， utilization， and anti-tumor activity of alkaloids， bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids， their representative derivatives， and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China ; Dwarfism/genetics* ; Humans ; Intellectual Disability ; Osteochondrodysplasias/genetics* ; Pedigree

【Objective】 To investigate the profile of Rh blood group antigen in pregnant women and hemolytic disease of the newborn (HDN) in Qingdao area. 【Methods】 10 597 pregnant women admitted in our hospital during October 2016 to February 2020 were selected and the ABO, Rh blood group system antigen (D, C, c, E, e) and the irregular antibody were detected, and positive antibody was further identified. The irregular antibody of Rh blood group in pregnant women was statistically analyzed according to the history of blood transfusion and pregnancy. Twelve HDN cases were studied, and the results of ABO, Rh blood group antigen and irregular antibody, antibody property identification, HDN test and blood routine test were retrospectively analyzed. 【Results】 Among 10 513 cases of Rh-positive pregnant women, the common phenotype was CCee>CcEe>Ccee>ccEE>ccEe; among 84 cases of Rh-negative pregnant wome, the common phenotype was ccee>Ccee> CCee> ccEE>ccEe. The positive rate of irregular antibody was 1.06% (112/10597) in 10 597 pregnant women, of which the Rh antibody was the highest, rated at 56.25% (63/112). For 64 pregnant women with positive antibodies, antibodies against Rh system were different from those against other systems when stratified by the history of blood transfusion (P<0.05) and pregnancy (P<0.05). Twelve neonates were diagnosed with Rh-HDN, with IgG anti-E in 6 cases, IgG anti-D 3, IgG anti-cE 1, IgG anti-C 1and IgG anti-c 1. Among them, 3 were seriously ill and treated with blood exchange. 【Conclusion】 As two-child policy was implemented, the incidence of Rh HDN had increased. ABO, RhD, C, c, E and e matched transfusion should be administered for women at childbearing age. Meanwhile, clinical termination of delivery was recommended for pregnant women, who probably develop Rh-HDN and are with critical situation. Rh phenotype matched fresh blood should be prepared, which has great clinical significance for rescuing newborns.

The prevalence of type 2 diabetes mellitus(T2DM)in China is about 9.1%.Compared with healthy adults, life expectancy for patients with T2DM at 60 years of age can be cut short by 7.3-9.5 years and time for a good quality of life by 11.1-13.8 years.It is important for elderly patients with T2DM to stay functionally active.Frailty, as a common geriatric syndrome, is an important factor affecting the functional status of the elderly, a strong predictor for disability, death and hospitalization, and also a strong predictor for adverse health outcomes in elderly patients with T2DM.This article reviews the relationship between frailty/sarcopenia and T2DM, and the management and treatment of elderly T2DM patients with frailty/sarcopenia.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.

Objective: To construct a hsa-microRNA-224(miR-224) lentiviral expression vector and to establish pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression. Methods: Pri-miR-224 gene fragment was designed and amplified by quantitative real-time polymerase chain reaction (qRT-PCR), and then loaded into GV369 lentiviral vectors (GV369-miR224) by gene recombination technology. GV369-miR-224 lentivrial expression vectors were then identified by PCR and DNA sequencing. The GV369-miR-224 vector fluid was then used to infect pancreatic mucinous cystadenocarcinoma MCC1 cell line to establish the MCC1 cell line stably over-expressing miR-224. The transfection efficiency of GV369-NC and GV369-miR-224 was observed under fluorescence microscopy; and the expression levels of miR-224 in MCC1, GV369-miR-224-MCC1 and GV369-NC-MCC1 cell lines were detected by RT-PCR. Results: The GV369-miR-224 lentiviral vectors were successfully constructed. GV369-miR-224-MCC1 and GV369-NC-MCC1 cells all emit green fluorescence under the fluorescence microscope. The expression level of miR-224 in GV369miR-224-MCC1 cell group was significantly higher than that in negative control GV369-miR-224-MCC1 group and blank control MCC1 cell group (23.45±1.94， 1.46±0.1 and 2.11±0.38, P<0.01), however, there was no significant difference between the two control groups (P>0.05). Conclusion: A pancreatic mucinous cystadenocarcinoma MCC1 cell line with stable miR-224 over-expression was successfully established, and this will provide a new cell model for exploring the function and pathogenesis of miR-224 in pancreatic mucinous cystadenocarcinoma.

OBJECTIVETo explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).

METHODSClinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation.

RESULTSThe average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/mto (27.9±3.5) kg/m(t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) μg/L to (0.7±0.3) μg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) μg/L to (1.5±0.7) μg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively.

CONCLUSIONAs for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.

Adolescent ; Adult ; Aged ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Weights and Measures ; C-Peptide ; blood ; physiology ; Caloric Restriction ; Combined Modality Therapy ; Comorbidity ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Diet Therapy ; methods ; Diet, Diabetic ; Endoscopy ; Fatty Liver ; complications ; surgery ; Female ; Food, Formulated ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Gout ; complications ; surgery ; Hashimoto Disease ; complications ; Humans ; Hypertension ; complications ; surgery ; Insulin ; blood ; physiology ; Lipids ; blood ; physiology ; Male ; Menstruation Disturbances ; complications ; surgery ; Middle Aged ; Obesity ; complications ; therapy ; Perioperative Care ; methods ; Thyroiditis ; complications ; Treatment Outcome ; Triglycerides ; blood ; physiology

Objective To evaluate the clinical characteristics of patients with growth-hormone adenoma (GHA) and summarize the diagnosis and treatment experience.Methods The clinical data of 338 GHA cases at the General Hospital of PLA from Jan. 1990 to Dec. 2016 were collected, of which 252 cases with more complete clinical data were retrospectively analyzed including their general situation, medical history, laboratory tests and auxiliary examinations, and treatment modalities and outcomes. Parts of the patients were followed up.Results The cases of hospitalized GHA patients have increased year by year since 1990, and the number of patients admitted in the last 3 years accounted for 56.2% of the total number of cases. The sex ratio for GHA patients was nearly 1:1. Age of visiting followed Gaussian distribution while the 41-50 age group occupied the largest part. The most typical sign is hand and foot enlargement (60.7%), followed by the hypertrophy of nasal ala. The most common symptoms are headache (42.5%), hypopsia, visual field defect and diplopia. More than half of GHA patients were complicated with prediabetes and diabetes (72.6%), sleep apnea (69.5%), goiter or thyroid nodularity (56.4%), cardiac insufficiency (57.0%) and colon polyp (54.1%); while the percentages of cases undergone the relevant examination in the total number of cases were as follows: 75g OGTT test (42.1%), polysomnography (23.4%), thyroid ultrasound (37.3%), echocardiogram (47.6%) and colonoscopy (14.7%); GHA was 23.37±1.42μg/L and IGF-1 was 804.28±273.93ng/ml on average; 85.0% of somatotroph tumors are macroadenoma. Surgery remains the mainstay of therapy to GHA, while medical therapy was selected by less patients. During the follow-up, only 38.0%of GHA patients can be contacted, among them the remission rate decreased to 40.5%. The positive rate of long-term remission evaluated by early postoperative GHA level was consistent with that confirmed by the long-term follow-up (χ2=3.368,P>0.05). Conclusions The number of hospitalized GHA patients have increased recent years. The common clinical signs and symptoms are somatic enlargement and nonspecific headache. Due to uncompleted screening, GHA associated complications are always misdiagnosed; It is essential to establish a sound model of follow-up to improve patients' quality of life. The early postoperative GHA levels may predict the prognosis of surgery.

Objective To investigate the local or systemic effects of initial periodontal therapy on peritoneal dialysis in patients with chronic kidney disease and periodontitis. Methods Sixty-one patients with both periodontitis and regular peritoneal dialysis were selected in this study and were randomly divided into observation group (n=31) and control group (n=30). Patients in observation group were given periodontal initial therapy (ultrasonic supragingival scaling and ultrasonic subgingival irrigation, drug, root planing, oral health education) and peritoneal dialysis treatment. Patients in control group were given only peritoneal dialysis treatment. Clinical parameters including plaque index (PLI), gingival index (GI) and probing depth (PD) were detected before and one month after treatment in two groups. The concentrations of high-sensitivity C-reactive protein (hs-CRP) in gingival sulcus fluid and serum samples were measured by immune transmission turbidity method in two groups. Results There were no significant differences in PLI, GI, PD, hs-CRP of gingival sulcus fluid, and serum hs-CRP before treatment between the two groups. After one-month initial therapy, all the indexes were decreased in observation group, which were significantly different compared with those before treatment (P<0.05). And all the indexes were significantly lower in observation group than those of control group. There were no significant differences in PLI, PD, GI, hs-CRP of gingival sulcus fluid, and serum hs-CRP between control group and observation group before treatment. Conclusion Periodontal initial treatment can improve the periodontal inflammation in patients with chronic kidney disease, and reduce the concentration of systemic inflammatory factor hs-CRP, decreasing the risk of infection.

Objective To evaluate effects of glucocorticoids on maxillary bone mineral density in rats with acute adriamycin-induced nephrotoxicity (ADR). Methods Forty rats were randomly divided into four groups, control group, glucocorticoids- treated group, ADR group and ADR + glucocorticoids- treated group. ADR group and ADR +glucocorticoids-treated group were given 4 mg/kg adriamycin injection via tail vein to establish ADR model. Control group and glucocorticoids-treated group were given 4 mg/kg saline injection via tail vein. After establishment of ADR model, glucocorticoids-treated group and ADR + glucocorticoids-treated group were intragastric administration of 30 mg/(kg · d) methylprednisolone for 10 weeks, and control group and ADR group were given the same volumes of normal saline. Values of bone calcium pigment (BGP), type Ⅰ collagen, N-terminal pro-peptide (PINP), β-Ⅰ type collagen C-terminal cross-linked telopeptide (CTX) were detected by ELISA. The micro-CT scan was used to measure Tb.Th, Tb.Sp, Tb.N, BVF and bone mineral density (BMD). Results Compared with other three groups, the levels of BGP and PINP were significantly decreased, and CTX were significantly increased in ADR + glucocorticoids-treated group (P<0.05). Micro-CT analysis showed that there was significant maxillae osteoporosis, including changes of porous micro architecture, lower BMD, decreased BVF, lower Tb.Th and widening Tb.Sp in ADR + glucocorticoids-treated group (P<0.05). There was no significant difference in Tb.N between four groups. Conclusion There is imbalanced bone metabolism in rat model of ADR. High-dose hormone therapy can accelerate the occurrence of osteoporosis, decrease bone metabolism, and affect bone structure.