ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD+)levels and nabothian cysts.This study aimed to assess the association between NAD+levels and nabothian cysts in healthy Chinese women. Methods Multivariate logistic regression analysis was performed to analyze the association between NAD+levels and nabothian cysts. Results The mean age was 43.0±11.5 years,and the mean level of NAD+was 31.3±5.3 μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and 84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from 37.4%to 21.6%from Q1 to Q4 of NAD+and the prevalence of single and multiple nabothian cysts also decreased across the NAD+quartiles.As compared with the highest NAD+quartile(≥34.4 μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD+Q1 was 1.89(1.14-3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD+levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD+levels of 28.0 to 35.0 μmol/L. Conclusion:Low NAD+levels were associated with an increased risk of total and multiple nabothian cysts.

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.
Male ; Humans ; Middle Aged ; Enteral Nutrition ; Intestines/surgery* ; Intestinal Diseases ; Abdomen/surgery* ; Anastomosis, Surgical ; Abdominal Injuries/surgery*

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

BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.
DNA Methylation/genetics* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Leukocytes, Mononuclear ; Monocytes ; Sjogren's Syndrome/genetics*

Objective To investigate the changes of mitochondrial metabolic functions of macrophages following Echinococcus multilocularis infections, so as to provide insights into the pathogenesis of alveolar echinococcosis. Methods Two groups were assigned according to different treatment methods. In the culture group, mouse leukemic monocyte macrophage RAW264.7 cells were cultured with 2 000 E. multilocularis at a ratio of 500∶1, while RAW264.7 cells in the control group were given no treatment. Then, both the culture and control groups were further divided into the 24 h and 72 h subgroups. Mitochondria were stained with MitoTracker^® Deep Red FM and the mean fluorescence intensity of macrophage mitochondria was measured with the Cytation 5 Cell Imaging Multi-Mode Reader. The mitochondrial DNA copy number was quantified using the quantitative real-time PCR (qPCR) assay, and the mitochondrial energy metabolism was monitored using the Seahorse XF assay. In addition, the mitochondrial reactive oxygen species and mitochondrial membrane potential were detected using flow cytometry. Results The mean fluorescence intensities of macrophage mitochondria were significantly lower in the 24 h (15 341 ± 2 532 vs. 17 823 ± 3 429; t = 6.379, P < 0.01) and 72 h (18 102 ± 3 505 vs. 21 511 ± 5 144; t = 17.680, P < 0.01) culture subgroups than in the corresponding control subgroups, and lower mitochondrial DNA copy numbers were measured in the 72 h culture subgroup than in the 72 h control group [(3.23 × 10⁹ ± 1.78 × 10⁷) vs. (4.39 × 10⁹ ± 3.70 × 10⁷); t = 8.85, P < 0.001]. The oxygen consumption rates were significantly greater in the 24 h [(241.70 ± 73.13) pmol/min vs. (69.05 ± 52.30) pmol/min; t = 7.89, P < 0.01] and 48 h culture groups [(249.50 ± 42.06) pmol/min vs. (60.28 ± 40.66) pmol/min; t = 8.64, P < 0.01] than in the corresponding control groups, and a higher extracellular acidification rate was seen in the 48 h culture group than in the 48 h control group ([ 111.6 ± 17.49) mpH/min vs. (35.05 ± 7.57) mpH/min; t = 16.90, P < 0.01]. In addition, flow cytometry detected higher mean fluorescence intensity of mitochondrial reactive oxygen species (58 264 ± 10 087 vs. 4 307 ± 97; t = 12.930, P < 0.01) and lower mitochondrial membrane potential (9.833% ± 2.285% vs. 2.667% ± 0.208%; t = 6.645, P < 0.01) in the 72 h culture group than in the control group. Conclusions E. multilocularis infection may impair mitochondrial functions and inhibit oxidative phosphorylation of macrophages, resulting in increased macrophage glycolysis. It is speculated that the alteration of macrophage metabolic states may contribute to the mechanisms underlying the development and progression of alveolar echinococcosis.

Objective: Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Peripheral artery disease (PAD) and liver fibrosis share many common metabolic dysfunctions. We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients. Methods: The study recruited 1,610 NAFLD patients aged ≥ 40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015. Fibrosis deterioration was defined as the NAFLD fibrosis score (NFS) status increased to a higher category at the follow-up visit. PAD was defined as an ankle-brachial index of < 0.90 or > 1.40. Results: During an average of 4.3 years' follow-up, 618 patients progressed to a higher NFS category. PAD was associated with 92% increased risk of fibrosis deterioration [multivariable-adjusted odds ratio ( ): 1.92, 95% confidence interval ( ): 1.24, 2.98]. When stratified by baseline NFS status, the for progression from low to intermediate or high NFS was 1.74 (95% : 1.02, 3.00), and progression from intermediate to high NFS was 2.24 (95% : 1.05, 4.80). There was a significant interaction between PAD and insulin resistance (IR) on fibrosis deterioration ( for interaction = 0.03). As compared with non-PAD and non-IR, the coexistence of PAD and IR was associated with a 3.85-fold (95% : 2.06, 7.18) increased risk of fibrosis deterioration. Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients, especially in those with IR. The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.
Adult ; Aged ; Aged, 80 and over ; Ankle Brachial Index ; China ; epidemiology ; Female ; Humans ; Liver Cirrhosis ; epidemiology ; etiology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; epidemiology ; etiology ; Peripheral Arterial Disease ; complications ; Prevalence ; Prospective Studies ; Risk Factors

Objective To investigate the cytotoxic effect mechanism of the unsaturated fatty acids on human cervical carcinoma of ME-180 cells.Methods The 2 × 108 cell · L-1 ME-180 cells were moved into the 96 hole culture plate,per hole 90 μL.Three concentrations of the drug groups:0.3,0.6,0.9 mg· L-1 unsaturated fatty acid (prepared with DMSO) per hole 90 μL.The 5-fluorouracil(5-FU) group:10mg · L-1 5-FU (prepared with phosphate buffer) per hole 10 μL.Control group:30 μL · L-1 DMSO per hole 10 μL.Each group set of four repeat hole,in saturated humidity condition of 37 ℃ and 5％ CO2 in 48 h.The inhibition rate and apoptosis rate of unsaturated fatty acids were detected with a trypan blue,thiazole blue (MTT),and flow cytometry method.Results When ME-180 cells were administered with the unsaturated fatty acids at the doses of 0.3,0.6,0.9 mg · L-1 for 48 h,ME -180 living cell count with the increase of drug concentration and action time is reduced.The cells proliferation inhibition rate were 43.35％,51.75％,66.45％ in three concentrations of the drug groups;apoptosis rate were 18.21％,23.11％,28.06％ in the three groups,respectively.Compared with the drug groups and the control group on the number of living cells,inhibition rate and apoptosis rate,the differences were statistically significant (P ＜0.01).Conclusion The unsaturated fatty acids has significant toxic effects on ME-180 cells.The toxic effect mechanism of the unsaturated fatty acids is related to inhibite proliferation on cell and induce-cell apoptosis.

Objective To study the effects of maca extract on exercise endurance and blood hormone levels in the rats. Methods Wistar rats treated with maca extract (2. 0, 4. 0, 8. 0 g/kg body weight) were freely swimming in the cir-culating water flow daily for 15 days. On the 16th day of experiment, the exercise endurance and blood noradrenaline (NA), estradiol (E2), and testosterone (T) levels of the rats were determined. Results The rats administered with maca extract at the doses of 2. 0, 4. 0, 8. 0 g/kg body weight for 15 d showed that the swimming time before sinking was in-creased by 32. 51%, 60. 04%, 106. 52%, the total swimming time was extended by 16. 99%, 56. 50%, and 101. 73%respectively ( P<0. 01 ); while the number of sinking was decreased by 18. 89%, 35. 89%, and 58. 06%, respectively (P< 0. 01), compared with those swimming rats without maca extract treatment. The noradrenaline level in the blood of rats treated with maca extract 2. 0, 4. 0, 8. 0 g/kg body weight was increased by 3. 30%, 6. 60%, and 16. 50%, respec-tively, compared with the control group, and increased by 42. 49%,47. 05%, and 60. 70%, respectively, compared with the swimming rats without extract treatment;the E2 level was increased by 132. 83%,102. 72%, and 62. 26% (P<0. 01) respectively, compared with the control group, while decreased by 23. 88%, 33. 72%, and 46. 95% (P<0. 01) respec-tively, compared with the swimming rats without extract treatment. The blood testosterone level was increased by 5. 11%, 37. 65%, and 123. 16% (P<0. 01) respectively, compared with the control group, and increased by 28. 98%, 68. 92%, and 173. 85%, (P<0. 01) respectively, compared with the swimming rats without extract treatment. Conclusions The results of this study demonstrate that maca extract has effect to resist fatigue and enhance exercise capacity in rats. The mechanism is associated with reduced blood E2 , and increased noradrenaline and testosterone levels in the blood of rats.

Objective To evaluate the quality of the hepatitis B report data on a pilot surveillance in Zhejiang Province from 2013 to 2015.Methods Hepatitis B report data of 6 pilots in Zhejiang Province from 2013 to 2015 were extracted from national notifiable infectious disease reporting system,including reported cases of hepatitis B,classification of hepatitis B cases and supplementary card information etc. To evaluate the accuracy of hepatitis B classification,information of supplementary cards was used to make classification diagnose for hepatitis B.Results A total of 3214 hepatitis B cases were reported in 6 pilot surveillance counties in Zhejiang Province between 2013 and 2015. Excluded 32 duplicated cases within the year and between years,3182 hepatitis B cases were actually reported,hepatitis B cases repeated reporting rate was 1%. A total of 2717 hepatitis B cases were correctly classified,and the accuracy rate of classification was 85.39%,showing an increasing trend (P<0.05). The proportion of accurate classification of reported hepatitis B by referring to the results of positive time of HBsAg and ALT from the supplementary card were 80.86% and 97.29% respectively. Among those reported acute hepatitis B cases,90.43% of them filled with anti-HBc IgM positive in supplementary card. The proportion of accurate classification of reported hepatitis B by referring to the information for liver puncture and the HBsAg and anti-HBs transform during the recovery period in supplementary cards were 0.19% and 5.13% respectively. Among those reported acute hepatitis B cases,0.69% of them were chronic or undetermined. Among those reported chronic hepatitis B cases,13.92% of them were acute,undetermined or HPV carrier. Five out of 3182 cases were unclassified,accounting for 0.16%.Conclusion The quality of classification diagnosis for hepatitis B should be improved in Zhejiang Province. Filling in the supplementary card is very beneficial for the classification of hepatitis B.