Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Purpose: Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. Materials and Methods: Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. Results: We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

OBJECTIVE: To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS). METHODS: Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up. RESULTS: The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (<0.01, <0.05), and HDL was increased significantly (<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (<0.05). CONCLUSION EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.
Acupuncture Points ; Electroacupuncture ; Female ; Humans ; Insulin Resistance ; Polycystic Ovary Syndrome ; therapy

Objective:To evaluate the safety, feasibility and operational performance of self-developed medical disposable portable endoscopy (YunSendo) for upper gastrointestinal endoscopy examination in Ba-Ma mini-pigs.Methods:A total of 10 Guangxi Ba-Ma mini-pigs were used in the experiment, and mucosal injury models were established in advance by biopsy forceps in esophagus, stomach, and duodenum. Each experimental animal underwent medical disposable portable endoscopy and Olympus endoscopy (GIF-Q260J) performed by two endoscopists separately. The time when the endoscope reached the duodenum, the number of detected mucosal injuries and endoscopic pictures of different parts with standard image acquisition were recorded. Endoscopic operational performance and endoscopic image quality were evaluated. Different endoscopists recorded experimental results with blind method. The procedures of the two endoscopic examinations were performed by coin-tossing method. The paired t test was used for statistical analysis. Results:There were no statistically significant differences in the insertion time and total operation time between medical disposable portable endoscopy and Olympus endoscopy ( (171.00±9.96) s vs. (164.00±17.84) s, (285.00±33.94) s vs. (273.40±23.46) s; t=1.289 and 1.281, P=0.230 and 0.232). There were no statistically significant differences in the percentage of time of clear visual field during endoscopy insertion and total operation between medical disposable portable endoscopy and Olympus endoscopy ((91.83±1.85)% vs. (91.52±1.51)%, (93.07±3.10)% vs. (92.06±2.57)%; t=0.401 and 0.689, P=0.698 and 0.508). Moreover, there were no statistically significant differences in the score of comprehensive operation performance, score of clear image number, score of image color recognition, score of image illumination, comprehensive score of image quality and number of detected mucosal injuries ((9.66±0.30) points vs. (9.86±0.15) points, (39.50±0.71) points vs. (39.30±1.06) points, (39.70±0.48) points vs. (39.40±0.70) points, (39.40±0.70) points vs. (39.50±0.71) points, (9.88±0.09) points vs. (9.85±0.20) points, 9.80±0.42 vs. 9.90±0.32; t=2.176, 1.000, 1.152, 0.317, 0.629 and 0.557, all P>0.05). There were no adverse events after operation in medical disposable portable endoscopy group and Olympus endoscopy group. Conclusions:The medical disposable portable endoscopy is safe and feasible for endoscopy examination in live animal models. Different parts of upper gastrointestinal tract and mucosal lesions can be clearly detected. The operational performance and the image quality are excellent, which is similar to Olympus endoscopy (GIF-Q260J).

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ²=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ²=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ²=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ²=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ²=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVE: To explore and quantify the intervention effect of auricular point sticking on perioperative psychological stress in patients with anorectal diseases. METHODS: Eighty patients who underwent anorectal surgery were randomly divided into an observation group (40 cases) and a control group (40 cases). The routine preoperative guidance, preoperative visits, and informed of the postoperative condition were received in the control group. On the basis of the treatment in the control group, auricular point sticking was immediately applied at Shenmen (TF), Shen (CO), Wei (CO), Gan (CO), Pi (CO), Pizhixia (AT), E (AT), Nie (AT) and Zhen (AT) in the observation group.The patients were pressed by themselves, 3 to 5 min per point each time, 5 times a day, and the contralateral auricular points were replaced every 2 or 3 days until 1 week after surgery. The Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Pittsburgh sleep quality index (PSQI) scores were compared between the two groups before and 7 days after surgery. RESULTS: There was no significant difference in the total HAMA scores between after and before surgery in the observation group (>0.05). The total HAMA score in the control group was higher than that before surgery (<0.05). The total HAMA score in the observation group after surgery was lower than that in the control group (<0.05). There was no significant difference in the total HAMD scores between the two groups before and after surgery (<0.05). There was no significant difference in the total HAMD scores between the two groups after the surgery (>0.05). The scores of somatic anxiety factor in the two groups were higher than those before surgery (<0.05). The scores of somatic anxiety factor in the observation group were lower than those in the control group (<0.05). The scores of psychotic anxiety factors in the two groups were lower than those before surgery (<0.05). There was no significant difference in the score of psychotic anxiety factors between the two groups (>0.05). The total score of PSQI in the two groups was lower than that before surgery (<0.05), and the total score of PSQI in the observation group was lower than that in the control group (<0.05). CONCLUSION Auricular point sticking can effectively improve some psychological stress problems during perioperative period in patients with anorectal diseases.
Acupuncture Points ; Acupuncture, Ear ; Anxiety Disorders ; therapy ; Humans ; Rectal Diseases ; surgery ; Stress, Psychological

The present study was designed to investigate the effect of cultivated Cordyceps sinensis (CCS) on leukemia-derived K562 cells, and further explore the underlying mechanisms. After routine culture of K562 cells, MTT assay was used to detect the effect of CCS on survivel of human leukemia cell lines K562;DAPI staining was used to observe the morphological changes of the nucleus and AO/EB staining was used to observe cell apoptosis. JC-1 staining was employed to detect the changes in mitochondrial membrane potential. Flow cytometry (FCM) was used to detect cell cycle distribution, and Western blot analysis was used to detect the expression levels of Bax, Bcl-2, caspase 3, caspase 8, cyclin D1, CDK2, and CDK4 in K562 cells. The results showed that CCS (0.345-5.524 g·L⁻¹) substantially suppressed proliferation of K562 cells and induced G₁/S phase arrest in a dose-dependent manner. DAPI and AO/EB staining indicated that cell apoptosis was significantly induced by CCS treatment, accompanied by decreased mitochondrial membrane potential demonstrated by JC-1 staining. Western blot results showed that CCS significantly increased the expression of Bax and, meanwhile, decreased the expression levels of Bcl-2, cyclin D1, CDK2, CDK4, caspase 3 and caspase 8. Collectively, our data demonstrated that CCS dose-dependently suppressed cell proliferation and induced cell apoptosis in K562 cells, and the mechanism might be associated with inducing cell cycle arrest, regulating Bcl-2/Bax ratio and activating the mitochondrial apoptosis pathway.

Objective To investigate and compare the curative effect between delayed percutaneous coronary intervention (PCI) for patients with acute myocardial infarction presenting 12-24 hours from symptom onset and medical therapy on acute myocardial infarction patients presenting with ST-segment elevation (STEMI). Methods Using a prospective,open,parallel,controlled research approach,186 patients with STEMI were divided into delayed PCI group(n=89),which received PCI within 12-24 hours after STEMI and medical therapy group(n=97),which received medical therapy after STEMI. All patients were followed up 1-6 months with average follow-up (5.6 ± 1.4) months. Data of hospitalization period, the cardiac structures detected by echocardiography such as left atrial diameter (LAD), left ventricular diastolic diameter(LVDd),left ventricular ejection fraction LVEF,left ventricular fractional shortening(LVFS),composite end point events and major adverse cardiac events(MACE)were compared between the two groups.Results Compared with medical therapy group, the hospitalization cycle was significantly shorter in delayed PCI group. Data of the LAD and LVDd were significantly decreased,but LVEF and LVFS were increased in delayed PCI group compared with those of medical therapy group at 30 d and 6-month follow-up. The incidence of MACE and composite end point events were significantly less in delayed PCI group than those of medical therapy group (P<0.05). Conclusion Delayed PCI treatment can decrease the time of hospital stay and decrease the incidence rates of MACE and composite end point events,and improve left ventricular function and prognosis of patients.