Etiology, Microbiological Isolates, and Antibiotic Susceptibilities in Inpatients with Refractory Auricular Perichondritis: A 10-Year Retrospective Study.

Purpose: This study aimed to elucidate the etiologies, microbiological profiles, antibiotic susceptibilities of bacteria and outcomes of patients with auricular perichondritis. Patients and Methods: This was a single-center retrospective study. Inpatients diagnosed with auricular perichondritis at a university teaching hospital in eastern China between January 2013 and December 2022 were included in this study. Results: A total of 127 patients were enrolled, with an average age of 50.6 ± 16.9 years. In addition to cases in which the etiology remained undetermined in 37% of the patients, postoperative infection emerged as the predominant cause (37.8%), followed by trauma (18.1%). Among the 61 cultured isolates, 21.3% were gram-positive bacteria, 55.7% were gram-negative bacteria, and 23.0% were fungal isolates. The most frequent isolate was Pseudomonas aeruginosa (30/61, 49.2%). Notably, the incidence of fungal infections was markedly higher among postoperative patients than among post-traumatic patients (41.7% vs 7.1%, p = 0.03). The proportions of gram-negative bacteria (60.0% vs 50.0%) and fungal isolates (28.6% vs 15.4%) exhibited an increasing trend during the period of 2018-2022, as compared to the previous period of 2013-2017. The bacterial isolates exhibited high susceptibility to vancomycin (100%), amikacin (100%), cefepime (94.6%), and ceftazidime (90.9%). In contrast, overall susceptibility to fluoroquinolones was relatively low (65.2-67.4%), demonstrating a declining trend in the susceptibility of Pseudomonas aeruginosa. Notably, 78.7% of the patients received an initial treatment regimen covering Pseudomonas aeruginosa. Within 30 days of discharge, 8.5% (6/71) experienced an infection recurrence. Conclusion: Auricular perichondritis predominantly originates from iatrogenic (postoperative) infections. Antibiotic therapy covering Pseudomonas aeruginosa is a sensible and appropriate empirical treatment in the majority of patients with auricular perichondritis. However, increased resistance to fluoroquinolones has become a notable concern, suggesting the need to seek new, more aggressive strategies.

Clinical characteristics and prognosis of primary small cell carcinoma of the breast: a propensity score-matched, population-based study.

OBJECTIVE: The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC). DESIGN: A retrospective cohort study. SETTING: Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. PARTICIPANTS: Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study. MATERIALS AND METHODS: Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB. RESULTS: Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system. CONCLUSION: PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.

Machine Learning Models for Blood Glucose Level Prediction in Patients With Diabetes Mellitus: Systematic Review and Network Meta-Analysis.

BACKGROUND: Machine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. OBJECTIVE: In a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. METHODS: PubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. RESULTS: In total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. CONCLUSIONS: Statistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. TRIAL REGISTRATION: PROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250.

Risk factors and survival prediction of young breast cancer patients with liver metastases: a population-based study.

Background: The risk and prognosis of young breast cancer (YBC) with liver metastases (YBCLM) remain unclear. Thus, this study aimed to determine the risk and prognostic factors in these patients and construct predictive nomogram models. Methods: This population-based retrospective study was conducted using data of YBCLM patients from the Surveillance, Epidemiology, and End Results database between 2010 and 2019. Multivariate logistic and Cox regression analyses were used to identify independent risk and prognostic factors, which were used to construct the diagnostic and prognostic nomograms. The concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the performances of the established nomogram models. Propensity score matching (PSM) analysis was used to balance the baseline characteristics between the YBCLM patients and non-young patients with BCLM when comparing overall survival (OS) and cancer-specific survival (CSS). Results: A total of 18,275 YBC were identified, of whom 400 had LM. T stage, N stage, molecular subtypes, and bone, lung, and brain metastases were independent risk factors for LM developing in YBC. The established diagnostic nomogram showed that bone metastases contributed the most risk of LM developing, with a C-index of 0.895 (95% confidence interval 0.877-0.913) for this nomogram model. YBCLM had better survival than non-young patients with BCLM in unmatched and matched cohorts after propensity score matching analysis. The multivariate Cox analysis demonstrated that molecular subtypes, surgery and bone, lung, and brain metastases were independently associated with OS and CSS, chemotherapy was an independent prognostic factor for OS, and marital status and T stage were independent prognostic factors for CSS. The C-indices for the OS- and CSS-specific nomograms were 0.728 (0.69-0.766) and 0.74 (0.696-0.778), respectively. The ROC analysis indicated that these models had excellent discriminatory power. The calibration curve also showed that the observed results were consistent with the predicted results. DCA showed that the developed nomogram models would be effective in clinical practice. Conclusion: The present study determined the risk and prognostic factors of YBCLM and further developed nomograms that can be used to effectively identify high-risk patients and predict survival outcomes.

Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model. M/Ms-specific Sirt3 knockout Sirt3f/f; CX3CR1-Cre (Sirt3 cKO) mouse was used to evaluate the role of Sirt3 on RSV treatment. Neuronal function and hematoma volume were assessed to indicate brain damage. The pro-inflammatory marker (CD16) and cytokine (TNF) were measured to evaluate the inflammatory effects. Our results showed that RSV treatment alleviates neurological deficits, reduces cell death, and increases hematoma clearance on day 7 after ICH. In addition, RSV effectively suppressed CD16+ M/Ms activation and decreased TNF release. In Sirt3 cKO mice, the protective effects of RSV were abolished, indicating the potential mechanism of RSV was partially due to Sirt3 signaling activation. Therefore, RSV could be a promising candidate and therapeutic agent for ICH and Sirt3 could be a potential target to inhibit inflammation.

Clinical characteristics and prognostic nomogram for patients with insular thyroid carcinoma: a population-based analysis.

BACKGROUND: Insular thyroid carcinoma (ITC) is an uncommon poorly differentiated thyroid malignancy. Due to its rarity, its demographic and clinicopathological features and survival remains unclear. The present study aimed to describe the features and survival of ITC, determine its prognostic factors, and establish a prognostic nomogram. METHODS: Patients with ITC were identified in the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The features and survival of patients with ITC and other thyroid carcinomas were compared after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for ITC. Moreover, overall survival (OS)- or cancer-specific survival (CSS)-specific nomograms were established to predict ITC prognosis. RESULTS: A total of 206 patients with ITCs were identified. The 1-, 2-, 5-, and 10-year OS rates of 206 patients with ITC were 90.3%, 82.0%, 62.2%, and 42.5%, respectively. The median OS was 93 months (95% CI, 73.0-140.0), while the median CSS was 141 months (95% CI, 93.0-173.0). After PSM analysis, the survival analysis of the matched cohort revealed that ITC had a worse clinical outcome than papillary thyroid cancer and follicular thyroid cancer, and better survival than anaplastic thyroid carcinoma. Multivariate Cox regression analysis demonstrated that age, N stage, M stage, and surgery were independent prognostic factors for both OS and CSS in ITC patients. The C-indices for the OS- and CSS-specific nomograms were 0.778 (95% CI, 0.724-0.832) and 0.808 (95% CI, 0.754-0.862), respectively. The calibration curve and ROC analysis indicated that the nomogram models exhibited a good discriminative ability. Decision curve analysis suggested that the nomogram models had a significant positive net benefit and were better than the traditional TNM staging system at predicting survival. CONCLUSION: ITC has distinct clinicopathological characteristics and survival compared to other thyroid carcinomas, and the established nomogram could predict the survival probability of patients with ITC accurately with a higher net benefit.

Quality control mechanism of mitochondria by 3,4-dihydroxybenzaldehyde through OGT-PINK1 pathway / 中国中药杂志

Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.

Clinical significance of loss of chromosome Y in patients with multiple myeloma / 中华检验医学杂志

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Yajieshaba prevents lipopolysaccharide-induced intestinal barrier injuryanti-inflammatory and anti-apoptosis.

OBJECTIVE: To investigate the protective effect of Yajieshaba (YJSB) on the intestinal barrier dysfunction induced by lipopolysaccharide (LPS). METHODS: C57BL/6 mice and rat intestinal epithelial cells were treated with LPS. Thiazolyl Blue Tetrazolium Bromide assay were used to detect cell viability. D-Lactate, diamine oxidase and myeloperoxidase and cytokines were determined by enzyme-linked immunosorbent assay. Western blot was used to detect apoptosis-related proteins and tight junction (TJ) proteins. Real-time quantitative polymerase chain reaction was used to quantify the levels of mRNA expression of cytokines. Histological analysis was performed by hematoxylin and eosin staining. An immunofluorescence staining assay was performed to determine the expression level of TJ protein. RESULTS: YJSB increased cell viability and decreased apoptosis, maintained intestinal permeability after LPS-induced. YJSB inhibited LPS-induced decrease of TJ protein expression, pro-inflammatory cytokine levels and neutrophil infiltration. CONCLUSION: YJSB protect against LPS-induced intestinal barrier dysfunction anti-inflammatory and anti-apoptosis, suggesting its therapeutic potential against intestinal barrier injury-related diseases.

Protective role of TLR9-induced macrophage/microglia phagocytosis after experimental intracerebral hemorrhage in mice.

INTRODUCTION: Intracerebral hemorrhage (ICH) causes devastating morbidity and mortality, and studies have shown that the toxic components of hematomas play key roles in brain damage after ICH. Recent studies have found that TLR9 participates in regulating the phagocytosis of peripheral macrophages. The current study examined the role of TLR9 in macrophage/microglial (M/M) function after ICH. METHODS: RAW264.7 (macrophage), BV2 (microglia), and HT22# (neurons) cell lines were transfected with lentivirus for TLR9 overexpression. Whole blood from C57BL/6 or EGFPTg/+ mice was infused for phagocytosis and injury experiments, and brusatol was used for the experiments. Intraperitoneal injection of the TLR9 agonist ODN1826 or control ODN2138 was performed on days 1, 3, 5, 7, and 28 after ICH to study the effects of TLR9 in mice. In addition, clodronate was coinjected in M/M elimination experiments. The brains were collected for histological and protein experiments at different time points after ICH induction. Cellular and histological methods were used to measure hematoma/iron residual, M/Ms variation, neural injury, and brain tissue loss. Behavioral tests were performed premodeling and on days 1, 3, 7, and 28 post-ICH. RESULTS: Overexpression of TLR9 facilitated M/M phagocytosis and protected neurons from blood-derived hazards in vitro. Furthermore, ODN1826 boosted M/M activation and phagocytic function, facilitated hematoma/iron resolution, reduced brain injury, and improved neurological function recovery in ICH mice, which were abolished by clodronate injection. The experimental results indicated that the Nrf2/CD204 pathway participated in TLR9-induced M/M phagocytosis after ICH. CONCLUSION: Our study suggests a protective role for TLR9-enhanced M/M phagocytosis via the Nrf2/CD204 pathway after ICH. Our findings may serve as potential targets for ICH treatment.

Influencing Factors of Horizontal Movement Distance of Bodies in High Falling Deaths / 法医学杂志

OBJECTIVES@#To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it.@*METHODS@#A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed.@*RESULTS@#The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups.@*CONCLUSIONS@#The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.

Crystal structure of SARS-CoV-2 papain-like protease

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

In vitro antibacterial effects of imipenem combined with conventional antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae / 中国基层医药

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

Clinical efficacy of short-term deep sedation after decompressive craniectomy with hematoma removal in patients with hypertensive intracerebral hemorrhage / 中国基层医药

Objective:To investigate the efficacy and safety of short-term deep sedation after conventional decompressive craniotomy with hematoma removal in patients with hypertensive intracerebral hemorrhage.Methods:Sixty patients with hypertensive intracerebral hemorrhage who underwent conventional decompressive craniotomy with hematoma removal in the People′s Hospital of Yueqing, China between March 2018 and May 2019 were included in this study. They were randomly divided into deep sedation and light sedation groups ( n = 30/group). The deep sedation group was administered propofol (0.6-1.2 mg/kg/h) combined with sedate fentanyl to achieve the level of sedation to Richmond Agitation-Sedation Scale (RASS) -3 to -4 points and to the level of pain to Critical Care Pain Observation Tool (CPOT) 0-1 point. The duration of sedation and analgesia was for 48 hours. The light sedation group was administered propofol (0.2-0.5 mg/kg/h) combined with sedate fentanyl to achieve the level of sedation to RASS -1 to -2 points and to the level of pain to CPOT 0-1 point. The duration of sedation and analgesia was rehemorrhage for 48 hours. Patients in the two groups were intravenously administered Urapidil to control blood pressure to be 120-160/60-90 mmHg. In addition, all patients were subjected to mechanical ventilation, dehydration, reduction of intracranial pressure, anti-infection and symptomatic treatment. At 0, 6, 12, 24 and 48 hours after surgery, heart rate, mean arterial pressure, intracranial pressure, recurrence of hemorrhage, ventilator-associated pneumonia, lower extremity deep venous thrombosis, and gastrointestinal bleeding were monitored. Results:At 6, 12, 24 and 48 hours after surgery, the heart rate, mean arterial pressure, and intracranial pressure in the deep sedation group were significantly lower than those in the light sedation group ( P < 0.05 or P < 0.01). The recurrence of rehemorrhage and the incidence of gastrointestinal bleeding in the deep sedation group were 3.33% (1/30) and 6.67% (2/30), respectively, which were significantly lower than those in the light sedation group [10.00% (3/30), 20.00% (6/30), χ2 = 1.071, 2.307, both P < 0.05). There were no significant incidences in ventilator-associated pneumonia [30.00% (9/30) vs. 23.30% (7/30), χ2 = 0.340, P > 0.05] and lower extremity deep venous thrombosis [10.00% (3/30) vs. 6.67% (2/30), χ2 = 0.340, P > 0.05]. Conclusion:Short-term deep sedation after conventional decompressive craniotomy with hematoma removal can lower the heart beat, mean arterial pressure, intracranial pressure, the postoperative recurrence of hemorrhage, and the incidence of gastrointestinal bleeding in patients with hypertensive cerebral hemorrhage.

Recent advances in emerging three-dimensional in vitro models for sport-related traumatic brain injury / 生物医学工程学杂志

Sports-related traumatic brain injury (srTBI) is a traumatic brain injury (TBI) caused by sports, which can result in cognitive and motor dysfunction. Currently, research on the molecular mechanism of srTBI and related drug development mainly relies on monolayer culture models and animal models. However, many differences exist in cell populations and inflammatory responses between these models and human pathophysiological processes. Most of the researches derived from the models can't effectively conducted translational research. Emerging three-dimensional (3D)

Should we remain hopeful? The key 8 weeks: spatiotemporal epidemic characteristics of COVID-19 in Sichuan Province and its comparative analysis with other provinces in China and global epidemic trends.

BACKGROUND: The COVID-19 spread worldwide quickly. Exploring the epidemiological characteristics could provide a basis for responding to imported cases abroad and to formulate prevention and control strategies in areas where COVID-19 is still spreading rapidly. METHODS: The number of confirmed cases, daily growth, incidence and length of time from the first reported case to the end of the local cases (i.e., non-overseas imported cases) were compared by spatial (geographical) and temporal classification and visualization of the development and changes of the epidemic situation by layers through maps. RESULTS: In the first wave, a total of 539 cases were reported in Sichuan, with an incidence rate of 0.6462/100,000. The closer to Hubei the population centres were, the more pronounced the epidemic was. The peak in Sichuan Province occurred in the second week. Eight weeks after the Wuhan lockdown, the health crisis had eased. The longest epidemic length at the city level in China (except Wuhan, Taiwan, and Hong Kong) was 53 days, with a median of 23 days. Spatial autocorrelation analysis of China showed positive spatial correlation (Moran's Index > 0, p < 0.05). Most countries outside China began to experience a rapid rise in infection rates 4 weeks after their first case. Some European countries experienced that rise earlier than the USA. The pandemic in Germany, Spain, Italy, and China took 28, 29, 34, and 18 days, respectively, to reach the peak of daily infections, after their daily increase of up to 20 cases. During this time, countries in the African region and Southeast Asian region were at an early stage of infections, those in the Eastern Mediterranean region and region of the Americas were in a rapid growth phase. CONCLUSIONS: After the closure of the outbreak city, appropriate isolation and control measures in the next 8 weeks were key to control the outbreak, which reduced the peak value and length of the outbreak. Some countries with improved epidemic situations need to develop a continuous "local strategy at entry checkpoints" to to fend off imported COVID-19.

Effect of (, TLZT) gel preparation on p53 /miR-502-5p /NF-κBp65 in synovial tissue of knee osteoarthritis / 中国骨伤

OBJECTIVE@#To observe effects of (, TLZT) gel preparation on p53, miR-502-5p, NF-κBp65 in synovial tissue of knee osteoarthritis (KOA), and to explore mechanism of TLZT gel preparation in treating KOA.@*METHODS@#Thirthy-six Wistar rats aged 8 weeks and weighed 200 to 220 g (meaned 208 g) were randomly divided into normal group, model group and traditional Chinese medicine (TCM) group, 12 rats in each group. KOA model was established by modified Hulth method. After 4 weeks of modeling, TCM group treated with TLZT gel preparation for external use, 3 times daily for 2 weeks;normal group and model group were fed normally without intervention. After treatment, morphological changes of specimens in each group were observed, changes of miR-502-5p in synovial tissue were detected by qPCR, and contents of p53, NF-κBp65, IL-1β, TNF-α, MMP-13 in synovial tissue were detected by qPCR and Western Blot respectively.@*RESULTS@#(1)Morphological observation of specimens showed that the articular cartilage in model group was hyaline and uneven, the synovial membranes were hypertrophic and proliferative with a large number of inflammatory cells infiltrating, the joint fluid was thicker in texture;the articular cartilage in TCM group was more transparent and smooth, synovial hyperplasia was mild with a small amount of inflammatory cell infiltration, the texture of articular fluid was clear and sparse. (2) Compared with normal group, content of miR-502-5p of synovial tissue in model and TCM group were increased, mRNA and expression of p53 decreased, expression of NF-κBp65, IL-1β, TNF-α, MMP-13 increased. (3)Compared with model group, content of miR-502-5p in synovial tissue of TCM group decreased (<0.05), mRNA and protein expression of p53 increased (<0.05), mRNA and protein expression of NF-κBp65, IL-1β, TNF-α, MMP-13 decreased (<0.05).@*CONCLUSION@#Expression of p53, miR-502 -5p, NF -κBp65 in synovial tissue is closely related to synovial hyperplasia and inflammatory reaction, TLZT gel preparation may reduce proliferation and inflammatory reaction of KOA synovium by regulating the expression of p53, miR- 502-5p, NF-κBp65 in synovial tissues.

Effect of an educational intervention on HPV knowledge and attitudes towards HPV and its vaccines among junior middle school students in Chengdu, China.

BACKGROUND: Little is known about the knowledge and attitudes towards human papillomavirus (HPV) and its vaccines among adolescents in mainland China. Also, limited information has been available on how to improve their knowledge and willingness towards HPV and its vaccines to ensure a successful vaccination program in the future. METHODS: This was a school-based interventional follow-up study. One urban and one rural junior middle school in Chengdu were selected by convenience sampling. At baseline, half of the grade one students were randomly selected as controls and the rest were interventions. A set of self-administered questionnaires on HPV and its vaccines were completed by both groups at baseline. After that, only the intervention group received a PowerPoint-oriented health education and finished the post-education questionnaires. One year later, both groups completed the same questionnaires as the follow-up survey. RESULTS: In total, 1675 students finished the pre-intervention questionnaires; 751 were from the control group and 924 were from the intervention group. Among them, only 34.3% had heard of cervical cancer/genital warts, while only 15.1% of them had ever heard of HPV. However, 55.2% of students showed their willingness to be vaccinated even before any intervention. Seven variables were found to be associated with the willingness to be vaccinated at baseline. Immediately after the intervention, 88.4% of students were willing to vaccinate themselves. After 1 year, the effectiveness of intervention remained but decreased. Compared with the control group, the intervention group was more aware about cervical cancer, HPV and its vaccines with statistical significance. However, the level of HPV knowledge and willingness to be vaccinated among the intervention group had significantly decreased compared with that immediately after the intervention (P < 0.001). CONCLUSIONS: The baseline level of knowledge on HPV, its vaccines, and cervical cancer was very low among junior middle school students in Chengdu, China. However, the willingness to be vaccinated seemed positive. School-based health education is effective and appropriate in increasing the awareness of HPV and willingness towards its vaccines. Regular health education on HPV and cervical cancer prevention at a shorter interval should be guaranteed to ensure continuous effectiveness.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

OBJECTIVE@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*DATA SOURCES@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*STUDY SELECTION@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*RESULTS@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*CONCLUSIONS@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.