Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective: To optimize the pre-column derivation high performance liquid chromatography (HPLC) content determination method of D-mannose and D-glucose as well as the content determination method of narinhenin in Dendrobium officinale and D. huoshanense, and compare the contents of D-mannose,D-glucose and narinhenin between D. officinale and D. huoshanense. Method: A pre-column derivation HPLC method modified by Chinese Pharmacopoeia(Ch.P) 2015 was used to simultaneously determine the contents of D-mannose and D-glucose,with acetonitrile-0.02 mol·L^-1 ammonium acetate solution as mobile phase for gradient elution. Kromasil 100-5 C₁₈ was performed with the wavelength set at 250 nm,and the flow rate was 1 mL·min^-1;column temperature was 30℃. HPLC content determination of narinhenin was performed on Kromasil 100-5 C₁₈ with the acetonitrile-methanol-0.4% phosphoric acid solution as mobile phase for gradient elution,and the wavelength was set at 290 nm; the flow rate was 0.8 mL·min^-1,and column temperature was 40℃. Result: D-mannose and D-glucose showed a good linear relationship within the range of 0.15-3.0 μg and 0.075-2.25 μg (r=0.999 9); and their average recoveries were 99.01% (RSD 2.1%) and 101.69% (RSD 2.0%) respectively. In addition, the other methodological researches such as repeatability and durability all met the requirements. The contents of D-mannose(C_m),D-glucose(C_g) and sum of them (C_m+C_g) were 12.75%-36.40%,2.93%-18.39% and 19.23%-54.58% in 43 batch of D. officinale. Almost all of the results except very few samples reached the D-mannose standard in Ch.P 2015, and the total content of D-mannose and D-glucose was also up to the total polysccharide standard in Ch.P. The correlation between content and origin was not significant. The contents of D-mannose(C_m),D-glucose(C_g) and sum of them (C_m+C_g) were 14.33%-29.47%,6.64%-15.20%,and 25.73%-44.37% in 12 batch of D. huoshanense. These contents and ratio of peak areas of D-mannose to D-glucose (A_m/A_g) were within the scope of D. officinale's; in addition, their average contents were basically the same with those in D. officinale (about 33%).Next,naringenin showed a good linear relationship within the range of 0.020 8-0.832 0 μg (r=0.999 9),and its average recovery was 101.96% (RSD 1.8%). The content of naringenin was 0.053 2-0.122 4 mg·g^-1 (average value of 0.081 0 mg·g^-1) in 11 batch of D. officinale, slightly higher than 0.040 3-0.090 0 mg ·g^-1 (average value of 0.068 3 mg ·g^-1) in 7 batch of D. huoshanense. All of these results of narinfenin did not reach the content lower limit in Ch.P. Conclusion: The method used to determinate the content of D-mannose and D-glucose is reproducible, and their sum content is possible to substitute the total polysccaride determination (with higher errors) in D. officinale; monosaccharide content determination can be used for quantitative quality control of D. huoshanense. However, it could not distinguish D. officinale and D. huoshanense by determining the contents of polysccharide,D-glucose,D-mannose and narinhenin, and shall be combined with other specificity methods for further identification.

Bicuspid aortic valve stenosis(BAVs) is a relative contraindication for transcatheter aortic valve replacement(TAVR) because of its abnormal anatomical structures and pathological characteristics that result in a lower device success rate in BAVs than that in patients with tricuspid aortic valve. However, with the optimization of TAVR strategies and the application of new-generation devices,the effect of TAVR treatment on BAVs patients has been improved. Thus, the article is to introduce the characteristics of BAVs and the progress of TAVR in treatment of BAVs.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have low immunogenicity and it is unclear whether insulin producing cells (IPCs) that differentiate from hUC-MSCs have low immunogenicity. OBJECTIVE:To investigate the immunogenicity of IPCs differentiating from hUC-MSCs in vitro and after IPCs transplantation into the host. METHODS: (1) The hUC-MSCs were induced to differentiate into IPCs according to the modified scheme. Flow cytometry assay was used to detect the immunophenotype and apoptotic rate of IPCs in a cytotoxicity test. (2) Cell counting kit-8 was used to detect the proliferative capacity of human peripheral blood mononuclear cells in the one-way mixed lymphocyte assay. (3) The IPCs were then transplanted into the abdominal cavity and left renal capsule of mice, and then the infiltration of immune cells was detected by flow cytometry and immunohistochemistry. RESULTS AND CONCLUSION: The IPCs highly expressed HLA-ABC and lowly expressed HLA-DR, CD40 and CD80. The apoptosis rate of IPCs increased with the increase of pre-sensitized splenocytes in the cytotoxicity test. In the one-way mixed lymphocyte assay, IPCs inhibited the proliferation of human peripheral blood mononuclear cells when the target ratio was 10:1 and 50:1. After IPCs transplantation, the number of lymphocytes was increased in the transplanted site. In summary, our results show that IPCs that differentiate from hUC-MSCs maintain low immunogenicity in vitro,but have some immunogenicity after transplantation into the host due to microenvironment changes.

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

Objective To evaluate the the protectice effect of dexmedetomidine combined limb remote ischemic postcondition on alleviating focal cerebral ischemic reperfusion injury in rats .Methods 48 healthy adult male SD rats were randomly divided into 4 groups(n= 12) :control group(C) ,limb remote ischemic postcondition group(R) and dexmedetomidine postconditioning group(D) and combination group(R/D) .The rat model of focal cerebral ischemic reperfusion injury was induced by middle cerebral artery oc‐clusion(MCAO) .The group C only received MCAO ,the left femoral artery was isolated without blocking ;the group R received 120 min brain ischemia ,the left femoral artery was occluded by 3 cycles of 10 min occlusion/10 min reperfusion before brain reperfu‐sion ;the group D received dexmedetomidine 3 μg/kg by intraperitoneal injection before brain reperfusion .The group R/D combined the above two kinds of processing method .The neurologic function was evaluated at 24 h of reperfusion and then the rats were sac‐rificed at 48 h of reperfusion .The brain was removed for determining the cerebral infarct volume .Results The neurologic function scores after 24 h reperfusion in the group D ,R and R/D were superior to those in the group C (P< 0 .01) .The rat cerebral infarct volume percentages after 48 h reperfusion in the group D ,R and R/D were significantly lower than those in the group C ( P <0 .01) .The infarct area volume percentage in the group R/D was significantly lower than that in the group R ,the difference showed statitistical significance(P< 0 .01) .The infarct volume percentage in group R/D was significantly decreased compared with the group D(P< 0 .05) .Conclusion Both dexmedetomidine and limb remote ischemic postcondition can attenuate the focal cerebral is‐chemic reperfusion injury in rats .Their combination can significantly reduce the cerebral infarction volume and has synergic protec‐tion effect .

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases (PubMed, Embase, ScienceDirect, and Wiley) and three Chinese databases (CNKI, WanFang, and VIP). Fifty-one articles (3 cohort studies and 48 case-control studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio (OR): 1.62; 95% confidence interval (CI): 1.39-1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer (OR: 1.04; 95% CI: 0.89-1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27 (95% CI: 1.07-1.50) and 1.66 (95% CI: 1.07-2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke (< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace (< 300 and ≥ 300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.
Breast Neoplasms ; China ; Cohort Studies ; Female ; Humans ; Occupational Exposure ; Odds Ratio ; Risk Factors ; Smoking ; Tobacco Smoke Pollution

OBJECTIVETo compare the enhanced recovery program after surgery (ERAS) with conventional perioperative management in patients undergoing radical resection for colorectal cancer.

METHODSThe ERAS protocol included a combination of evidence-based and consensus methodology. A total of 597 consecutive patients undergoing elective colorectal resection were randomized to either the ERAS(n=299) or the control group(n=298). Outcomes related to nutrition and metabolism index, stress index, and recovery index were measured and recorded.

RESULTSDemographics and operative parameters were similar between the two groups(P>0.05). The nutritional status of patients in the ERAS group was improved after surgery compared with that of the control group. On postoperative day (POD) 1, the HOMA-IR in the ERAS group was significantly lower than that in the control group(P<0.01). The cortisol level in the control group was elevated on both POD 1(P<0.01) and POD 5(P<0.01) compared to the preoperative level. However, the cortisol level was not increased until POD 5(P<0.01) in the ERAS group. The levels of TNF-α, IL-1β, IL-6, and IFN-γ were reduced in the ERAS group, indicating less postoperative stress responses compared with the control group. In addition, ERAS group was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay [(5.7±1.6) d vs. (6.6±2.4) d, P<0.01] and expense[(15 998±2655) RMB vs. (17 763±3059) RMB, P<0.01] were reduced in the ERAS group. Twenty-eight patients(9.4%) in the control group and 29(9.7%) in the ERAS group developed complications, while the difference was not statistically significant(P>0.05).

CONCLUSIONERAS protocol alleviates surgical stress response and accelerates postoperative recovery without compromising patient safety.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Perioperative Care ; methods ; Prospective Studies ; Young Adult