Objective To explore the relationship between tumor necrosis factor (TNF) gene polymorphisms in donors and recipients and the incidence and severity of acute graft-versus-host diseases (aGVHD) after unrelated allogeneic hematopoietic stem cell transplantation (alIo-HSCT). Methods Single nucleotide polymorphisms (SNPs) of TNFα-238 (G/A), TNFα-857 (C/T), TNFα-863 (C/A), TNFα-1031 (T/C), TNFβ + 252 (A/G) were analyzed by Multiplex SNaPshot analysis in 76 pairs of donors and recipients. Results Transplantation involving donors with TNFα-857 CC genotype resulted in a higher incidence of grade Ⅱ-Ⅳ aGVHD than donors with CT genotype (91.3% vs 8. 7% , P =0. 039). In the 23 patients with grade Ⅱ-Ⅳ aGVHD, no patients had TNFβ +252 AA genotype, 19 (82.6%) had GA genotype and 4 (17.4%) had GG genotype. There was a significant difference in the distribution pattern of the TNFβ +252 (AA, GA and GG) genotypes in these patients (P =0.03). There was no significant association of TNFα-238 (G/A), TNFα-863 (C/A) and TNFα-1031 (T/C) polymorphisms with the risk of aGVHD. Conclusion These results suggest donor TNFα-857 CC genotype is related to a higher incidence of grade Ⅱ -Ⅳ aGVHD, and patients with TNFβ +252 AA genotype have protection against the risk of grade Ⅱ -Ⅳ aGVHD.

High altitude polycythemia (HAPC) had become one of the main common chronic diseases, which had seriously threatened the health of Plateau people. In the Tibetan medicine classic bookSi-Bu Yi-Dian, there were recordings on HAPC treatment methods and medications, which had the unique advantages of identified therapeutic effect with little side effect. This article analyzed Tibetan medicine in the prevention and treatment of HAPC from aspects such as etiology and pathogenesis, clinical treatment advantages and modern innovation study. Questions were also raised on lacking of standardization on HAPC clinical effectiveness, as well as Tibetan medicine compound material basis and action mechanisms were unclear. It was proposed that based on the inheritance of Tibetan medicine theoretical basis and clinical therapeutic effect, the Tibetan medicine original thinking should be combined with modern science and technology, in order to strengthen the analysis of ancient literature collection in HAPC treatment and data mining in medication experiences. The clinical treatment standards and medication plan should be standardized. Methods of systems biology, such as metabolomics, can be used in the further study of the scientific connotation of HAPC treatment by Tibetan medicine.

Objective To provide valid data and useful genetic counseling in the clinical application of non‐invasive prenatal test (NIPT) ,fetal chromosomal disorder were screened by massive parallel sequencing and made a follow‐up study .Methods Preg‐nant women with Down screening in high‐risk were screened by NIPT ;NIPT verified high‐risk individuals were suggested for kary‐otyping ;and we follow up on whoever showed low risk by NIPT before and after their deliveries .Results (1)Totally 1 676 cases of pregnant women were tested by NIPT ,25 cases prompted to be abnormal ,with an abnormal rate of 1 .49% ,karyotype analysis re‐sults in 12 cases of abnormalit ,the accuracies of NIPT for T21 ,T18 ,XO ,XXY ,and XYY were 99 .93% ,100 .00% ,99 .66% , 100 .00% ,100 .00% respectively ;the accuracy of NIPT for women with advanced paternal age and twins were both 100 .00% ;kary‐otyping positive individuals underwent abortion ,which gives a prenatal intervention rate of 100 .00% .(2)Out of 1 651 cases of NIPT low risk testers ,1 468 cases were successfully followed up ,with a 88 .91% success rate .We found chromosome abnormality with one case of inversion of chromosome 9 (maternal) .(3)Ultrasound‐detection possessed 98 .17% accuracy and 7 .69% in detec‐tion rate;in high‐risk pregnant woman ,Down screening had an accuracy of 0 .88% and false positive rate of 99 .12% ;98 .71%women were avoided prenatal diagnosis via NIPT .Conclusion Compare to ultrasound and maternal plasma screening ,NIPT is a far more accurate prenatal screening approach .To build effective follow‐up and service systems of NIPT is necessary to reduce birth de‐fects in medical institutions .

Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Vesico-Ureteral Reflux ; diagnosis ; therapy

AIMTo evaluate the hypoglycemic effect of chitosan-coated and sodium alginate-coated insulin liposomes after oral administration in mice.

METHODSInsulin-liposomes were prepared by reverse-phase evaporation. Chitosan and alginate coating was carried out by mixing liposomal suspension with chitosan and sodium alginate solutions, followed by incubation. The particle size and morphology of insulin-liposomes were determined using laser light scattering instrument and transmission electron microscopy (TEM). The entrapment efficiency was analyzed using HPLC and ultracentrifuge. The protection of insulin from peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of polysaccharide-coated insulin liposomes were investigated using the glucose oxidase method after oral administration in mice.

RESULTSThe particle size of uncoated, chitosan-coated and alginate-coated insulin-liposomes was (138 +/- 31) nm, (230 +/- 20) nm and (266 +/- 19) nm, respectively. All insulin-liposomes were of spherical or ellipsoidal shape. The entrapment efficiencies were 81.6%, 73.5% and 68.7%, respectively. Insulin was protected from tryptic digestion by chitosan-coated liposomes and protected from peptic digestion by alginate-coated liposomes. The hypoglycemic effects of insulin-liposomes, coated with 0.1% chitosan and 0.1% sodium alginate, were observed.

CONCLUSIONChitosan-coated and sodium alginate-coated liposomes were shown to reduce peptic or tryptic digestion on insulin, and enhance enteral absorption of insulin.

Administration, Oral ; Alginates ; Animals ; Blood Glucose ; metabolism ; Chitin ; analogs & derivatives ; chemistry ; Chitosan ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Glucuronic Acid ; Hexuronic Acids ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; administration & dosage ; pharmacology ; Liposomes ; Male ; Mice ; Particle Size ; Random Allocation ; Technology, Pharmaceutical ; methods

A method was developed for the determination of eight steroid hormones ( estrone, α/β-estradiol, estriol, testosterone, epitestosterone, progesterone and testosterone propionate ) in butter samples by gel permeation chromatography ( GPC) purification-followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were first extracted by ethylacetate/cyclohexane (1:1, V/V) and the extract was later degreased by GPC column. Then, the GPC concentrate was separated using a C18 column ( 100 mm í2. 0 mm i. d. , 3. 0 μm) with gradient elution of acetonitrile/water. Finally, the steroid hormone components were qualitatively and quantitatively determined by mass spectrometer with electrospray ionization in multi reaction monitoring mode. Using matrix matched external standard method, good linearity in response could be obtained in the concentration range of 1 . 0-20 . 0 μg/kg with correlation co-efficiency larger than 0 . 999 . The detection limits of the method were 0. 04-0. 30 μg/kg and the quantification limit was 1. 0 μg/kg. At the spike levels of 1. 0, 2. 0 and 4. 0μg/kg, the recoveries of hormones were within the range of 64. 1%-110%, and the relative standard deviation ( RSD) was less than 11%. The results show that the method is accurate and reliable, and meets the requirements for determination of 8 steroid hormones in butter samples.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of butoconazole in human plasma. Human plasma samples of 0.2 μL were pretreated by a single step protein precipitation procedure and analyzed using a high performance liquid chromatography (HPLC) electrospray tandem mass spectrometer system. The compounds were eluted isocratically on an Inertsil ODS-SP column (100 mm×2.1 mm, 3 μm), ionized using a positive ion atmospheric pressure electrospray ionization source and analyzed using multiple reaction monitoring (MRM) mode. The ion transitions monitored were m/z 412.8→165.1 for butoconazole and m/z 453.4→230.3 for the internal standard. The chromatographic run time was 3.5 min per injection, with retention time of 2.47 min and 2.15 min for butoconazole and repaglinide, respectively. The method was validated to be linear over the range of 20 to 8000 pg/mL (r>0.999) by using a weighted (1/x(2)) quadratic regression. The mean recovery rate was more than 86.7%, and the intra- and inter-day precision of the quality control samples (QCs) was less than 8.3% and the accuracy ranged from 96.0% to 110.2%, which indicated that the quantitative method was reliable and accurate. The method is simple, rapid, and has been applied successfully to a pharmacokinetics study of butoconazole nitrate suppositories in healthy Chinese females.

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Objective:To investigate the clinical efficacy of laparoscopic resection of retrorectal cystic lesions.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 58 patients undergoing laparoscopic resection of retrorectal cystic lesions in the Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from August 2012 to August 2019 were collected. There were 5 males and 53 females, aged from 15 to 70 years, with a median age of 38 years. All the 58 patients underwent laparoscopic resection of retrorectal cystic lesions and the combined operation through the transsacral approach was chosen according to the patient condition. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) postoperative histopathological examination; (4) follow-up. Patients were followed up regularly using outpatient examination once every 6 months during the first postoperative year and once every 12 months after the first postoperative year. The recurrence of cysts was evaluated by computed tomography or magnetic resonance imaging examinations during the follow-up up to August 2020. Measurement data with normal distribution were represented as Mean± SD and measurement data with skewed distribution were described as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations: of the 58 patients, 54 cases underwent laparoscopic resection of retrorectal cystic lesions and 4 cases underwent laparoscopic resection of retrorectal cystic lesions combined with the transsacral approach operation. One of the 58 patients who had a huge cyst surrounding the rectum underwent transverse colostomy after repairing the damage of separated posterior wall of rectum. Two cases underwent preventive transverse colostomy because the external rectal wall heat injury could not be excluded after separation of the tight adhesion between cyst and rectum. The operation time and volume of intraoperative blood loss were (123±56)minutes, 20 mL(range, 5?500 mL) of 54 cases who underwent laparoscopic resection of retrorectal cystic lesions and (232±38)minutes, 90 mL(range, 30?800 mL) of 4 cases who underwent laparoscopic resection of retrorectal cystic lesions combined with the transsacral approach operation, respectively. (2) Postoperative situations: 7 of the 58 patients had complica-tions. Of the 7 patients, 2 cases had postoperative rectal fistula and were cured after the treatment of transverse colostomy combined with pelvic drainage, 2 cases had postoperative urinary tract infection and were relieved after anti-infection treatment, 2 cases had urinary retention after removal of catheter and were recovered after 3 weeks of re-indwelling catheter, and 1 case had poor incision healing of transsacral and was healed after wound dressing change. The duration of postoperative hospital stay of the 58 patients was (7±4)days. (3) Postoperative histopathological examination: results of the postoperative histopathological examination showed that there were 26 of 58 patients with epidermoid cyst, 20 patients with teratoma (2 cases with mature teratoma accompanied by mucinous adenocarcinoma and 1 case with mature teratoma accompanied by neuroendocrine carcinoma), 10 patients with dermoid cyst, and 2 patients with tailgut cyst. (4) Follow-up: 57 of the 58 patients were followed up for 2-85 months, with a median follow-up time of 51 months. Of the 57 patients who were followed up, 1 patient was diagnosed with buttock subcutaneous cyst at postoperative 8 months and treated with local excision, 1 patient was diagnosed with a small presacral cyst recurrence by pelvic magnetic resonance imaging at postoperative 6 months and continued follow-up as the cyst without obvious enlargement, and the other 55 patients had no cyst recurrence.Conclusion:The laparoscopic resection of retrorectal cystic lesions is safe and feasible.

OBJECTIVETo evaluate the impact of neoadjuvant chemoradiation on perineal wound healing following abdominoperineal resection(APR) for lower rectal cancer.

METHODSData of 93 patients who underwent APR for low rectal cancer between January 2005 and January 2009 in Peking Union Medical College Hospital were reviewed, including patients who received neoadjuvant chemoradiation (n=29) and those undergoing surgery alone(n=64). Perineal wound healing was the primary outcome measurement. Condition of wound healing was classified as good, moderate, and poor and was compared between the two groups.

RESULTSTwenty nine patients in the neoadjuvant group received preoperative regional radiation(50 Gy, 25 fractions/5 weeks) with synchronous FOLFOX4 chemotherapy(fluorouracil and oxaliplatin). In the neoadjuvant group, wound healing after APR was good in 18 patients(62.1%), moderate in 6(20.7%), and poor in 5(17.2%). In patients who had surgery alone, wound healing after APR was good in 41 patients(64.1%), moderate in 15(23.4%), and poor in 8(12.5%). There was no significant difference in the incidence of wound infection(poor wound healing)between the two groups(P=0.773).

CONCLUSIONNeoadjuvant chemoradiation therapy is not associated with increased perineal wound infection following abdominoperineal resection for low rectal cancer.

Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Perineum ; surgery ; Rectal Neoplasms ; surgery ; therapy ; Rectum ; surgery ; Wound Healing