Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To understand HIV self-testing and related factors in men who have sex with men (MSM) in Shijiazhuang. Methods: From August to September 2020, convenient sampling was used to recruit MSM in Shijiazhuang. Online questionnaires were used to collect information about their demographic characteristics, sexual behaviors and HIV self-testing. logistic regression model was used to analyze the related factors associated with HIV self-testing. Results: In the 304 MSM respondents, 52.3% (159/304) had HIV self-testing in the past 6 months, and 95.0% (151/159) used fingertip blood HIV detection reagent. Self-purchase was the main way to obtain HIV testing reagents (45.9%, 73/159), followed by supply from MSM social organization (44.7%, 71/159). The reasons for having HIV self-testing were non-specific testing time (67.9%, 108/159) and privacy protection (62.9%,100/159), the reasons for having no HIV self-testing included inability of using (32.4%, 47/145), being unaware of HIV self-testing reagent (24.1%, 35/145), and worry about inaccurate self-testing results (19.3%, 28/145). Multivariate logistic regression analysis showed that being 18-29 years old (aOR=2.68, 95%CI: 1.20-5.94), obtaining free HIV self-testing kits in recent 6 months (aOR=8.61, 95%CI: 4.09-18.11) and making friends through Internet and social software (aOR=2.68, 95%CI: 1.48-4.88) were positive factors for having HIV self-testing. Conclusion: HIV self-testing is a more flexible and convenient way to detect HIV in MSM, and the promotion of HIV self-testing in MSM should be strengthened to further increase the HIV detection rate in this population.
Male ; Humans ; Adolescent ; Young Adult ; Adult ; Homosexuality, Male ; Self-Testing ; Sexual and Gender Minorities ; HIV Testing ; Sexual Behavior

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

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

The application of special acupoints for different primary symptoms of chronic gastritis in ancient literature of acupuncture and moxibustion was analyzed and summarized. With keywords, electronic and manual retrieval of ancient literature being performed to establish a database, the association rules were performed with SPSS Modeler 18. As a result, ① among all the 2243 items included, 109 items mentioned special acupoints (excluding those only mentioned crossing acupoint). The frequency of special acupoints was 2554 (71.7%), and the special acupoints on the spleen meridian, the stomach meridian, the conception vessel were frequently used. The frequency of five- point was highest, followed by front- points. ② The special acupoints for four main primary symptoms of chronic gastritis, "stomachache" "vomiting and regurgitation" "belching and acid regurgitation" and "epigastric fullness", included Zusanli (ST 36), Neiguan (PC 6), Zhongwan (CV 12), Gongsun (SP 4), Taibai (SP 3). In addition, the back- points were also selected to treat the primary symptoms other than "epigastric fullness". Zhangmen (LR 13) was added to treat "belching and acid regurgitation". The combination of Neiguan (PC 6) and Gongsun (SP 4) showed the strongest correlation; due to different primary symptoms, the combination had different emphasis.

The characteristics of syndrome differentiation and the experience of professor were briefly introduced for the treatment of infertility of ovulation disturbance, including three aspects, named the thought of diagnosis and treatment, the therapeutic method and the acupoint prescription, as well as the clinical case report. Academically, professor is deeply influenced by professor , the acupuncture master of Xin'an school and Lingnan school. Regarding the treatment of gynecological diseases, the academic thought of professor - and - is contributed. Professor attaches the importance to the syndrome differentiation based on meridian and collateral, supplemented by the syndrome differentiation of , , and blood, cold and heat, as well as the deficiency and excess. In clinical treatment, the acupoints are selected specially from the conception vessel, the governor vessel, the thoroughfare vessel and the belt vessel. The extra meridians are equally important as the regular ones in the treatment, especially the belt vessel. Additionally, the treatment focuses on communicating the congenital with the acquired one, regulating the liver and benefiting the kidney, as well as adjusting the heart, the spleen and the stomach to ease the uterus. Simultaneously, the great consideration is paid to the menstruation regulation so as to promote pregnancy.

The combination of ginkgo ketoester tablet - donepezil (GD) is a popular combination commonly used in clinic for the treatment of Alzheimer's disease. To evaluate the learning and memory improving ability of different proportions of the two drugs. We optimized the ratio of GD for treatment of dementia using a mouse model. Dementia was induced by multiple neuronal damages in mice. The experimental protocols were approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine and all the procedures were strictly conducted in accordance with ethical principle of animal use and care. Morris water maze, brain hematosylin-eosin staining and the changes of the neurotransmitters and related enzymes in the plasma or brain tissues were tested to determine the effect of GD on dementia mice. The results showed that the dementia mice were significantly different from the normal group in terms of behavior, pathological sections and related indicators. Compared to the dementia mice, partial administration groups could improve learning and memory ability as well as indexes in the blood and brain tissues. Both the principal component analysis and multi-attribute comprehensive index methods were used to comprehensively evaluate the total effect of GD on anti-dementia. The results showed that the combination of two drugs at the dose of 0.5 to 1 times was in a dose-effect relationship, and the dose of 1 (the clinical equivalent) had the best treatment effect. Then based on the optimal dose, GD 1∶1 had best effect, which was consistent with the clinical use of two drugs. This provides scientific basis for more effective application of the compatibility between ketoester tablet and donepezil for modern clinic medicine.

BACKGROUND: Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. The VVV of BP was calculated using five metrics, including standard deviation (SD), coefficient of variation (CV), variation independent of mean, average real variability, and successive variability (SV) of measurements, obtained over a 24-month measurement period. Hazard ratios and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression models for the associations of variability in BP with risk of CVD. RESULTS: A total of 894 CVD events were observed during a median follow-up of 49.5 months. The hazard ratio in the highest quintile of SD of SBP was 1.24 (95% CI, 1.01 to 1.52) compared with patients in the lowest quintile. The association between higher VVV of DBP and risk of CVD was not consistent across different metrics and sensitivity analyses. CONCLUSION: Higher VVV of SBP was associated with an increased risk of CVD, irrespective of the mean SBP level. Future studies are needed to confirm these findings.
Blood Pressure ; Cardiovascular Diseases ; China ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Follow-Up Studies ; Humans ; Retrospective Studies

Objective: To explore the protective effect and the preliminary mechanism of Dihuang Yinzi on cerebral ischemia-reperfusion injury in rats. Method: The middle cerebral artery occlusion (MCAO) model was established. Totally 90 SD rats were randomly divided into 6 groups:sham operation group, model group, nimodipine group (0.01 g·kg^-1) and high, medium, low-dose Dihuang Yinzi groups (38.80, 19.40, 9.70 g·kg^-1), with 20 rats in each group.The modified neurological severity score (mNSS) was assayed at the 7^th, 14^th, 28^th days after operation, and the volume of cerebral infarction, pathological changes of brain tissue, the BrdU positive cells and mRNA levels of Notch1, Jagged1 and Hes1 in subventricular zone(SVZ)were observed respectively by triphenyl tetrazolium chloride(TTC) stain, htorylin eastin(HE) stain, immunofluorescence technique and reverse transcriphase polymerase chain reaction(Real-time PCR) methods at the 28^th day after the operation. Result: The mNSS on the 7^th, 14^th, 28^th days of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly lower than that of model group(P<0.05, P<0.01). On the 28^th day, the percentage of cerebral infarction volume in brain tissue volume of high, medium-dose Dihuang Yinzi groups and nimodipine group were smaller than that of model group(P<0.01).HE staining showed that the necrosis and softening lesions of brain tissue were not obvious in rats of high, medium-dose Dihuang Yinzi groups and nimodipine group, with neuronal cell and neuroglial cell proliferation. On the 28^th day, the BrdU positive cells in SVZ of the above 3 groups were significantly higher than model group(P<0.05, P<0.01), and the high-dose Dihuang Yinzi group was significantly higher than nimodipine group(P<0.05). On the 28^th day, the mRNA levels of Notch1, Jagged1 and Hes1 of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly higher than those of model group(P<0.05, P<0.01), the mRNA level of Hes1 of nimodipine group was higher than that of high, medium, low-dose Dihuang Yinzi groups(P<0.05, P<0.01). Conclusion: Dihuang Yinzi can improve the nerve function defect of MCAO rat model, and reduce the volume of cerebral infarction and the pathological changes of brain tissue, thus playing a protective role in cerebral ischemia-reperfusion injury rats. Its mechanism may be related to the activation of the Notch signaling pathway, and the up-regulation of expressions of Notch1, Jagged1 and Hes1 mRNA, thus promoting the proliferation of NSCs.