Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Objective: To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Methods: Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. Results: The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P<0.05). After treatment, the scores of primary and secondary symptoms decreased in all three groups, with statistically significant intra-group differences (all P<0.05); the scores of primary symptoms were significantly different between the massage plus moxibustion group and the drug group (P<0.05); the scores of secondary symptoms in the massage plus moxibustion group and the massage group were significantly different from that in the drug group (both P<0.05). The differences in the time to recover normal bowel movement frequency among the three groups were not statistically significant (P>0.05). Conclusion: Ginger-partitioned moxibustion plus pediatric massage compared with pediatric massage or smecta monotherapy shows superior clinical efficacy in treating infantile diarrhea due to spleen deficiency, and has the advantages of appetite improvement, physique strengthening and short course.

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

OBJECTIVE: To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR). METHODS: Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells. RESULTS: EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P<0.05). No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups (P>0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05). CONCLUSIONS EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60　and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.

Objective: To analyze the urinary iodine status of urban and rural residents in some areas of Gansu Province and its related influencing factors, and to provide certain references for scientific iodine intake of urban and rural residents in Gansu Province. Methods: Subjects in Gansu Province with normal thyroid function were recruited in the investigation of thyroid diseases and iodine nutritional status, conducted a questionnaire survey and measured height, weight, waist circumference, collected 1 urine sample, and tested their urinary iodine levels. The urinary iodine levels of different groups were compared based on different gender, region, age, body weight, the waist, and salt intaking. The affecting factors of urinary iodine levels were analyzed by multiple linear regression models. Results: Totally 1 964 subjects were recruited, including 1 099 males, and 865 females. The age was (41.23 ± 14.75) years old. The median urinary iodine of the selected group was 225.60 (158.80, 311.58) μg/L. The urinary iodine level of rural residents was significantly higher than that of urban residents [μg/L: 249.80 (180.58, 336.88) vs 206.25 (148.03, 280.33), Z=-8.015, P < 0.05], and there was no significant difference between the urinary iodine levels of male and female [μg/L: 222.40 (161.60, 298.90) vs 230.60 (158.00, 326.40), P > 0.05]. The composition ratio of < 100 μg/L group in rural areas was lower than that in urban areas (5.14% vs 8.27%, χ²= 7.45, P < 0.05), and the composition ratio of ≥300 μg/L group was higher than that in urban areas (34.93% vs 21.51%, χ²= 43.87, P < 0.05). The composition ratio of ≥300 μg/L group in male was lower than that in female (24.57% vs 31.21%, χ²= 10.73, P < 0.05). The multiple linear regression analysis showed that lived in rural areas, age, moderate and severe salt intaking, student, and weight were independently correlated with urinary iodine levels (β= 0.074, -0.001, 0.059, 0.034, 0.096, -0.003, P < 0.05). And the urinary iodine levels were decreased with age and weight increased (P < 0.05). Conclusions At present, the iodine nutrition level of urban and rural residents in some areas of Gansu Province is generally over the adequate level. The urinary iodine level of rural residents is higher than that of urban residents. In the future, we should pay attention to the impact of different living areas, salt intaking and body weight on urinary iodine levels to prevent thyroid diseases.

Objective:To investigate the effects of Hydroxychloroquine on cell apoptosis in peripheral blood mononuclear cells of systemic lupus erythematosus and its mechanisms.Methods:The peripheral blood mononuclear cells of 30 active SLE patients and 15 healthy persons were separated for cell culture.There were four groups:control group,SLE group and HCQ 5 mg/L and HCQ 25 mg/L group.MTT was used to measure the inhibitory effect.Annexin V/PI flow cytometry was performed to analyze cell apoptosis.Western blot was used to evaluate the expressions of PI3 K,pAKt,mTOR,BCL-2,BAX and caspase-3.Besides,the PBMCs of SLE patients were treated with HCQ 25 mg/L and the PI3K/Akt pathway inhibitor LY294002 20 μmol/L and its cell growth inhibition and apoptosis were observed.Results:Compared with the control group,the cell growth inhibition and apoptosis rate of SLE patients group were significantly increased(P＜0.05);while the cell growth inhibition and apoptosis rate of HCQ 5 mg/L and 25 mg/L were increased significantly than the SLE patients group(P＜0.05).Compared with SLE patients group,the expression levels of PI3K,pAKt,mTOR and BCL-2 of HCQ group were significantly increased while the expression of BAX and caspase-3 decreased significantly (P＜ 0.05).The PI3K/Akt pathway inhibitor LY294002 could block the PBMCs apoptosis of SLE patients.Conclusion:Hydroxychloroquine can promote the PBMCs apoptosis of SLE patients by PI3K/Akt signaling pathways.

Objective To study the inhibitory effect of ursolic acid on the proliferation of human papillary thyroid carcinoma cell line TPC-1 in vitro. Method TPC-1 cells were treated with different concentrations of ursolic acid (control group:0μM, experimental group:3μM , 6μM, 12μM);MTT assay was used to observe the effect of the growth of TPC-1 cells on different concentrations of ursolic acid at the same time;Apoptosis and cell cycle distribution of TPC-1 cells were treated with ursolic acid by flow cytometry;The expression of Bcl-2, Bax and Caspase-9 mRNA in TPC-1 cells were treated with ursolic acid by QRT-PCR;The expression of Bcl-2, Bax and Caspase-9 protein in TPC-1 cells were treated with ursolic acid by Western blot. Results MTT assay showed that ursolic acid inhibited the proliferation of TPC-1 cells in a concentration and time-dependent manner, and the IC50 at 24 h, 48 h and 72 h was 14.21 μM, 10.56 μM, 10.39 μM; Flow cytometry showed that ursolic acid inhibited the apoptosis of TPC-1 cells in a concentration-dependent manner, and the growth of TPC-1 cells was arrested in S phase;QRT-PCR showed that Bcl-2, Bax and Caspase-9 mRNA were expressed in the control and experimental groups, ursolic acid inhibited the expression of Bcl-2 mRNA in a concentration-dependent manner and up-regulated the expression of Bax and Caspase-9 mRNA;Western blot results showed that Bcl-2, Bax and Caspase-9 were expressed in the control and experimental groups, ursolic acid inhibited the expression of Bcl-2 protein in a concentration-dependent manner and up-regulated the expression of Bax protein and Caspase-9 protein. Conclusion Ursolic acid can significantly inhibit the proliferation and induce apoptosis of human papillary thyroid TPC-1 cells, providing some ideas for the treatment of thyroid cancer.

Objective To explore the protective effect of gallic acid in Phyllanthus emblica on high glucose－induced apoptosis of pancreatic islet β cells, and to provide a reference for the discovery of natural compounds for the treatment of diabetes. Methods In vivo experimental model, wistar male rats were used as in vivo subjects and 50 mg/kg STZ was injected intraperitoneally. After the model was successfully established, 25 mg/kg of gallic acid was given orally, and the positive drug was Sitagliptin. After 4 weeks of administration, the blood was taken and the pancreas was removed for HE staining. Western blot was used to measure the expression of NLRP3 and TXNIP in pancreatic tissue in high sugar state. In vitro model, insulinoma cell line INS－1 cells were used as in vitro targets to establish high levels. In sugar－induced apoptosis model, INS－1 cells were cultured in glucose－free RPMI 1640 complete medium supplemented with 25 mmol/L glucose. Gallic acid was used as the test sample. Experiments were divided into normal controls, high－sugar models, and low, medium and high levels of gallic acid groups. The cell viability was measured by MTT assay. The mRNA expression of NLRP3 and TXNIP in INS－1 cells was detected by QPCR and Western blot, and the expression of NLRP3 and TXNIP protein was detected.Results (1) INS－1 cells were cultured in a medium with glucose concentration of 25mmol/L for 48h, and the apoptosis rate was increased compared with the control group (P＜0.01), indicating that the apoptosis model was established successfully under high glucose conditions. (2) 10, 5, and 2.5 μmol/L GA were used to treat the control group and the high glucose model group cells respectively. The survival rate of the control group did not change significantly (P＞0.05) . Compared with the control group, the expression of NLRP3 and TXNIP in INS－1 cells in the high glucose model group was significantly different (P＜0.05);the protein expression level was significantly downregulated after GA treatment, and there was a statistical difference (P＜0.05) . Compared with the control group, the expression of NLRP3 protein in INS－1 cells in the high glucose model group was statistically different (P＜0.01), and the protein expression level was significantly downregulated after GA treatment (P＜0.01) ; The protein expression level was up－regulated (P＜0.05);the protein expression level after GA treatment was significantly down－regulated (P＜0.05); (4) The expression of NLRP3 and TXNIP mRNA in INS－1 cells was increased in the high glucose model group compared with the control group (P＜0.01) ; The expression of protein was significantly down－regulated after GA treatment (P＜0.01) . Conclusion The cells were cultured for 48 h in glucose－free RPMI 1640 complete medium supplemented with 25 mmol/L glucose. GA has no effect on the proliferation of normal INS－1 cells. GA protects INS－1 cells from apoptosis under high glucose conditions. The mechanism may be related to GA down－regulation of NLRP3 and TXNIP gene expression.