ObjectiveTo investigate the survival and adverse reactions of patients with unresectable cholangiocarcinoma after stereotactic body radiation therapy （SBRT）. MethodsA total of 27 patients with unresectable solitary cholangiocarcinoma without metastasis who underwent SBRT in The Fifth Medical Center of Chinese PLA General Hospital from February 2012 to July 2020 were enrolled. The prescribed dose to planning target volume was 42-60 Gy in 5-8 fractions， with 5-11 Gy/fraction. Among these patients， five patients were also treated with chemotherapy and transcatheter arterial chemoembolization. The 6-， 12-， 18-， and 24-month overall survival （OS） rates， progression-free survival （PFS） rates， and local control （LC） rates were used as the assessment indices for treatment outcome； Common Terminology Criteria for Adverse Events v.4.03 was used to evaluate adverse reactions； the Kaplan-Meier method was used to calculate OS， PFS， and LC rates. ResultsThe median follow-up time was 17 months. For all 27 patients， the 6-， 12-， 18-， and 24-month OS rates were 100%， 88%， 57.5%， and 47.9%， respectively； the 6-， 12-， 18-， and 24-month PFS rates were 74.1%， 58.6%， 47.9%， and 35.9%， respectively； the 6-， 12-， 18-， and 24-month LC rates were 96.3%， 91.9%， 84.8%， and 76.4%， respectively. No grade 3 or above toxic reactions were observed. Five patients were diagnosed with radiation-induced liver injury， but there was no death due to radiation-induced liver injury. ConclusionSBRT is safe and effective in the treatment of unresectable cholangiocarcinoma， with relatively high survival rate， PFS rate， and LC rate and low toxicity， and therefore， SBRT can be used as an alternative treatment method for patients with cholangiocarcinoma who are not candidates for surgery.

Objective:To evaluate the relationship between postoperative delirium and preoperative frailty in elderly patients undergoing non-cardiac surgery.Methods:Elderly patients undergoing non-cardiac surgery at our hospital from March 2019 to July 2022 were collected and their age, comorbidities, gender, smoking history, type of surgery, preoperative albumin, duration of surgery, duration of anesthesia, postoperative hypotension, educational level, nutritional status, American Society of Anesthesiologists (ASA) Physical Status classification, postoperative admission to ICU or not, intraoperative bleeding and preoperative frailty status were collected. The patients were divided into delirium group and non-delirium group according to whether postoperative delirium occurred. The risk factors for postoperative delirium were analyzed by multivariate logistic regression analysis, and the receiver operating characteristic curve was drawn to analyze the value of risk factors in predicting postoperative delirium.Results:There were 74 cases in delirium group and 321 cases in non-delirium group, and the incidence of postoperative delirium was 18.7%. There were statistically significant differences in terms of age ≥70 yr, education level of junior high school and below, poor nutritional status, ASA Physical Status classification Ⅲ, postoperative admission to ICU, proportion of frailty and intraoperative bleeding volume between delirium group and non-delirium group ( P<0.05). The results of logistic regression analysis showed that age, educational level, nutritional status, ASA Physical Status classification, intraoperative bleeding and frailty were all independent risk factors for delirium ( P<0.05). The area under the receiver operating characteristic curve of preoperative frailty predicting postoperative delirium was 0.672 (95% confidence interval 0.605-0.740). Conclusions:Preoperative frailty is an independent risk factor for postoperative delirium in elderly patients undergoing noncardiac surgery, which can predict the occurrence of postoperative delirium to some extent.

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.

Objective:To explore the differential expression profile of miRN in the development of diabetes nephropathy (DN), and further explore the mechanism of miR-126-5p involved in high glucose induced injury of renal tubular epithelial cells.Methods:Firstly, we downloaded existing chip data from the Gene Expression Integrated Database (GEO) and used GEO2R, miRanda, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to mine differential miRNAs. Subsequently, a high glucose induced HK-2 cell injury model was used and divided into three groups: high glucose model group, si-HOTAIR group, and si HOTAIR+ miR-126-5p inhibitor group. The three groups of cells were sequentially transfected with siRNA-NC, siRNA-HOTAIR, and siRNA-HOTAIR+ miR-126-5p mimic, and cultured in a medium containing 60 mmol/L glucose. Flow cytometry was used to detect changes in apoptosis levels in each group, while cell counting kit-8 (CCK-8) was used to detect changes in cell proliferation.Results:Through data mining analysis using GEO, it was found that compared to ordinary mice, DN mice had 74 upregulated miRNAs and 80 downregulated miRNAs in their kidney tissue. Enrichment analysis results showed that miRNAs could target signaling pathways such as Wnt, PKG, MAPK, and Rap1, and miR-126-5p was significantly downregulated. In the high glucose induced HK-2 cell injury model, the experimental results showed that the inhibitory effect on cell proliferation activity was more significant at a high glucose concentration of 60 mmol/L ( P<0.05); High glucose stimulation significantly reduced the expression of miR-126-5p ( P<0.05). The results of flow cytometry showed that compared with the high glucose model group, the apoptosis rate of the si-HOTAIR group significantly decreased ( P<0.05), while the apoptosis rate of the si-HOTAIR+ miR-126-5p inhibitor group significantly increased ( P<0.05). The CCK-8 experiment showed that compared with the high glucose model group, the cell viability of the si-HOTAIR group significantly increased ( P<0.05); The cell viability of the si-HOTAIR+ miR-126-5p inhibitor group was inhibited ( P<0.05). Conclusions:miR-126-5p can inhibit high glucose induced apoptosis in HK-2 cells and protect them.

Objective:To explore the characteristics of intestinal flora in female patients with type 2 diabetes mellitus (T2DM) with comorbid coronary heart disease.Methods:Female patients with T2DM from September 2019 to November 2020 were enrolled in this study and divided into 2 groups stratified by coronary heart disease: 22 patients with coronary heart disease(T2DM+ CHD group) and 49 patients with simple T2DM group(T2DM group). Thirty-one healthy females were selected as the normal control group(NC group). The abundance of intestinal flora, the difference in intestinal flora and its relationship with indicators such as glycosylated hemoglobin and fasting blood glucose was analyzed by the real-time fluorescent quantitative PCR detection technology in the three groups.Results:The abundance of Prevotella in the T2DM group was lower, and Roseburia inulinivorans and Faecalibacterium prausnitzii in the T2DM+ CHD group were lower, while Bacteroides and Enterococcus spp in the T2DM+ CHD group were higher compared with NC group, respectively( P<0.05). The abundance of Bacteroides and Enterococcus spp in the T2DM+ CHD group was lower than that in the T2DM group( P<0.05). Spearman correlation analysis showed that the abundance of Faecalibacterium prausnitzii and Eubacterium rectale was negatively correlated with obesity while abundance of Bacteroides and Enterococcus spp was positively correlated with HbA 1C and fasting blood glucose. The abundance of Bacteroides was positively correlated with TCH and TG(all P<0.05). Logistic regression analysis showed that Bacteroides and Enterococcus spp were independent influencing factor of the development of female patients with T2DM and CHD. Conclusion:Female T2DM and T2DM with CHD had intestinal flora imbalance, which was related to a variety of glucose and lipid metabolism indicators, and might be closely related to the occurrence of T2DM and CHD. Bacteroides and Enterococcus spp were independent influencing factors of the development of female patients with T2DM and CHD. Regulating the intestinal flora can provide ideas for the prevention and treatment of T2DM with CHD in female.

Objective:To investigate the effects of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine (Tempol) on the expressions of hypoxia inducible factor-1 α (HIF-1α)/vascular endothelial growth factor (VEGF) and lung development in premature neonatal rats under intermittent hypoxia (achieved by supplying a low concentration of oxygen).Methods:The intermittent hypoxia model was established.Caesarean section of rats was performed at 21 days of gestation when the fetal rats were estimated to be in labor.A total of 192 premature neonatal rats survived and were randomly divided into 6 groups according to random number table method: air control+ saline group, air control+ Tempol group, constant oxygen + saline group, constant oxygen + Tempol group, intermittent hypoxia + saline group, and intermittent hypoxia + Tempol group, 32 rats in each group.On the 7 th, 14 th and 21 st day of birth, the lung tissues of 8 neonatal preterm rats in each group were taken.Malondialdehyde (MDA) and total antioxidant capacity (TAOC) were detected by chemical analysis.The mRNA and protein levels of HIF-1α and VEGF were detected by real-time fluorescence quantitative PCR (qPCR) and immunohistochemistry, respectively.Another 8 neonatal rats in each group were taken for pulmonary function test on the 21 st day after birth. One- way ANOVA and SNK- q test were used for comparison among and between groups, respectively. Results:Compared with the constant oxygen + saline group, the intermittent hypoxia + saline group showed mild pulmonary septal thickening, increased MDA, decreased TAOC, elevated mRNA and protein expression levels of VEGF and HIF-1 α, and decreased lung function indexes.The differences were statistically significant (all P<0.05). Compared with the corresponding saline group, the intermittent hypoxia + Tempol group had decreased MDA and increased TAOC, and the differences were statistically significant at 14 d[MDA(3.09±0.45) nmol/(mg·pr) vs.4.02±0.30) nmol/(mg·pr), TAOC(3.13±0.31) U/(mg·pr) vs.(2.44±0.22) U/(mg·pr)]and 21 d[MDA(2.87±0.43) nmol/(mg·pr) vs.(4.47±0.56) nmol/(mg·pr), TAOC(3.47±0.35) U/(mg·pr) vs.(2.31±0.32) U/(mg·pr)] (all P<0.05). Compared with the corresponding saline group, the mRNA and protein expression of HIF-1 α and VEGF decreased in the intermittent hypoxia+ Tempol group, and the decrease in the mRNA expression of HIF-1 α was statistically significant at 14 d (2.11±0.60 vs.2.88±0.59) (all P<0.05). Lung function indexes, including tidal volume[(0.41 ± 0.01) mL vs.(0.36±0.02) mL], minute respiratory ventilation[(35.48 ± 2.95) mL vs.(30.62±2.27) mL], maximum expiratory flow[(2.19 ± 0.19) mL/s vs.(1.51±0.19) mL/s]and dynamic lung compliance[(2.65 ± 0.40) mL/cmH 2O vs.(1.83±0.34) mL/cmH 2O, 1 cmH 2O=0.098 kPa]increased (all P<0.05). Conclusions:Tempol can alleviate the lung injury induced by intermittent hypoxia under the intervention of a low concentration of oxygen to premature newborn rats and improve their lung function.

ObjectiveTo investigate the efficacy and safety of sequential lenvatinib therapy after stereotactic body radiotherapy (SBRT) in the treatment of advanced primary liver cancer. MethodsA total of 18 patients with advanced primary liver cancer who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from October 2018 to May 2019 were enrolled, among whom there were 4 patients with BCLC stage B liver cancer and 14 patients with BCLC stage C liver cancer. The prescribed dose of planning target volume was 48-55 Gy (median 50 Gy) in 6-9 fractions, and the median of single dose was 6 (5-9) Gy per fraction. Oral administration of lenvatinib was given since 1 week after SBRT was finished, with a median medication time of 9.5 (3.6-25.8) months. Follow-up was performed once a month for the first 3 months after treatment and once every 3 months after 3 months of treatment. The Kaplan-Meier method was used to calculate overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate, and the incidence rates of adverse reactions and complications were also observed. ResultsUp to the follow-up on November 30, 2020, a total of 8 patients died, among whom 3 died of liver failure, 3 died due to tumor progression, 1 died of perforation of gallbladder, and 1 died of gastrointestinal bleeding. At 3, 6, 9, 12, and 18 months of treatment, the OS rates were 100%, 94%, 83%, 72%, and 67%, respectively, the PFS rates were 100%, 67%, 50%, 22%, and 17%, respectively, and the LC rates were 100%, 94%, 94%, 94%, and 94%, respectively; the median OS time was ＞18 months, and the median PFS time was 9 months. Of all patients, 1 (6%) had a grade 3 adverse reaction during SBRT and 2 (11%) experienced a grade 3 adverse reaction during lenvatinib treatment, and no fatal adverse reaction was observed. ConclusionIt is preliminarily proved that sequential lenvatinib therapy after SBRT is an effective and safe treatment method for advanced primary liver cancer.

Objective To investigate the effects of different degrees of autophagy on the apop-tosis of GABAergic neurons in spinal dorsal horn of postherpetic neuralgia model mice. Methods Forty-eight Kunming mice,approximately 6-8 weeks of age and weighing 18-22 g,were randomly divided into four groups by a random digital generator of SPSS 19.0:resinotoxin+autoph-agy induction group (group PHN+Rapa),resinotoxin group (group PHN),resinotoxin+autophagy inhibitor group (group PHN+3-MA)and blank control group (group C),12 mice in each group. Group C was given no treatment,and the other groups were given intraperitoneal injection of 0.2 μg/g resiniferatoxin (RTX)to prepare PHN model.After successful model establishment,group PHN+Rapa was given Rapamycin (1 μg·kg-1·d-1),physiological saline was given to group PHN, group PHN+3-MA was given 2 μg·kg-1·d-1autophagy inhibitor 3-MA.The intraperitoneal injection was continued for 14 day.The mechanical withdrawal threshold (MWT)and the latent period of thermal withdrawal latency (TWL)were detected and the mice were killed after stability. The segments of L4-6spinal cord were extracted and the relative expressions of bcl-2,Bax and autoph-agy-associated protein LC3 were detected by western blot.Detection of the number of apoptotic cells in the spinal cord by fluorescence Tunel.The number of GABA intermediate neurons in the dorsal horn of the spinal cord was labeled by immunofluorescence.Results Compared with group C,the rel-ative expression level of Bax protein increased significantly,the LC3-II/I ratio and the number of ap-optotic cells increased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in spinal dorsal horn were significantly reduced in other groups (P<0.05).Compared with group PHN,the LC3-II/I ratio and the relative expression level of Bax protein,the number of apoptotic cells increased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in the spinal dorsal horn were significantly decreased of group PHN+Rapa (P<0.05).Compared with group PHN,the relative expression level of LC3-II/I ratio and Bax protein, the number of apoptotic cells decreased significantly,the relative expression level of Bcl-2 protein and the number of GABA neurons in spinal dorsal horn increased significantly of group PHN+3-MA,(P<0.05).Conclusion Over activation of autophagy may be one of the mechanisms leading to the ap-optosis of GABA neurons in the dorsal horn of the spinal cord in postherpetic neuralgia.

Objective: To analyze the antimicrobial resistance profile in Chinese children. Methods: This was a prevalence survey. From January 1 through December 31, 2016, the isolates were collected from 10 tertiary children hospitals in China. Antimicrobial susceptibility testing was carried out by routine laboratory methods. The penicillin susceptibility of streptococcus pneumonia and Meropenem susceptibility of gram-negative bacteria were detected by E-test and disk diffusion method respectively. Antimicrobial susceptibility results were interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) Guideline 2016. The data of antimicrobial susceptibility testing of isolates from either the different patients (neonatal group and non-neonatal group) or various sources were analyzed by WHONET 5.6 software. Results: A total of 56 241 isolates were collected, of which 41.5% (23 328 isolates) were gram-positive organisms and 58.5% (32 886 isolates) gram-negative organisms. The five leading pathogens were Escherichia coli (7 995/56 214, 14.2%), Straphylococcus aureus (6 468/56 214, 11.5%), Streptococcus pneumonia (6 225/56 214, 11.1%), Haemophilus influenza (5 435/56 214, 9.7%) and Klebsiella pneumonia (4 523/56 214, 8.0%). The Meropenem resistance rates of Klebsiella pneumonia, Enterobacter cloacae, Escherichia coil, Pseudomonas aeruginosa, Acinetobacter baumonia isolates were 27.4% (326/1 189) , 8.1% (29/358) , 2.0% (27/1 362) , 19.5% (34/174) , 49.7% (230/463) in neonatal group and 15.4% (512/3 327) , 4.8% (40/841) , 2.3% (151/6 564) , 13.7% (252/1 840) , and 53.4% (860/1 611) in non-neonatal group. The Methicillin-resistant Staphylococcus aureus (MRSA) rates of neonatal group and non-neonatal group were 46.2% (649/1 404) and 33.3% (1 668/5 010) . The penicillin non-susceptible rates of Streptococcus pneumonia in the two groups were 17.6% (6/34) and 18.2% (1 121/6 158) respectively. The β-lactamase positive rates of Haemophilus pneumonia isolates in the neonatal group and non-neonatal groups were 33.8% (47/139) and 44.4% (2 345/5 282) respectively. Conclusion This investigation highlights the worrisome trend of antimicrobial resistance in children, especially among neonatal patients in China.

Objective·To study the hemodynamic parameters of uterine at midluteal phase in patients with early recurrent spontaneous abortion (ERSA) and the effect of aspirin on them. Methods·Transvaginal color Doppler ultrasonography was used to measure the parameters of uterine blood flow and the endometrial thickness at midluteal phase of 271 women with ERSA (ERSA group) and 66 women without a history of recurrent spontaneous abortion (control group). Then ERSA group were administered with aspirin 50 mg/d orally for 2 months and other individualized treatment, and the effect of aspirin on parameters of uterine blood flow and the early pregnancy outcome of them were observed. Results·At midluteal phase, the endometrium was significantly thinner in ERSA group than that in control group. Pulsatility index (PI) of endometrial blood flow and mean PI (mPI), mean resistance index (mRI), and mean systolic/diastolic ratio value (mS/D) of uterine arteries were statistically significantly higher in ERSA group in comparison to control group (P<0.05). Following aspirin treatment, resistance to uterine blood flow reduced significantly in ERSA group (P=0.000), and the endometrial thickness increased in the patients with endometrial thickness less than 7 mm (P=0.000). Only 163 ERSA patients were re-examined by transvaginal color Doppler ultrasonography after aspirin treatment, among whom 136 women was pregnant after individualized treatment. Among these pregnant patients, 97 cases were pregnant for more than or equal to 12 weeks, while 10 cases aborted during the first 12 weeks, and the early pregnancy outcomes of the other 29 cases were still unclear. Conclusion·In comparison with normal fertile women, ERSA patients have significantly higher resistance to uterine blood flow and thinner endometrium. Aspirin can improve uterine blood perfusion, which improves early pregnancy outcome.