[Observation on the efficacy of continuous veno-venous hemodia-filtration combined with hemoperfusion HA380 in the treatment of 15 cases of heat stroke with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS). METHODS: A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU) of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated. RESULTS: There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation II (APACHE II) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) µg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) µg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (µmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [µg/L: 490.90 (164.98, 768.05) vs. 3 000.00 (293.00, 3 000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2 107.0 (729.0, 2 449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. CONCLUSIONS: CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.

Venous Thrombus Embolism in Polytrauma: Special Attention to Patients with Traumatic Brain Injury.

Venous thrombus embolism (VTE) is common after polytrauma, both of which are considered significant contributors to poor outcomes and mortality. Traumatic brain injury (TBI) is recognized as an independent risk factor for VTE and one of the most common components of polytraumatic injuries. Few studies have assessed the impact of TBI on the development of VTE in polytrauma patients. This study sought to determine whether TBI further increases the risk for VTE in polytrauma patients. A retrospective, multi-center trial was performed from May 2020 to December 2021. The occurrence of venous thrombosis and pulmonary embolism from injury to 28 days after injury was observed. Of 847 enrolled patients, 220 (26%) developed DVT. The incidence of DVT was 31.9% (122/383) in patients with polytrauma with TBI (PT + TBI group), 22.0% (54/246) in patients with polytrauma without TBI (PT group), and 20.2% (44/218) in patients with isolated TBI (TBI group). Despite similar Glasgow Coma Scale scores, the incidence of DVT in the PT + TBI group was significantly higher than in the TBI group (31.9% vs. 20.2%, p < 0.01). Similarly, despite no difference in Injury Severity Scores between the PT + TBI and PT groups, the DVT rate was significantly higher in the PT + TBI group than in the PT group (31.9% vs. 22.0%, p < 0.01). Delayed anticoagulant therapy, delayed mechanical prophylaxis, older age, and higher D-dimer levels were independent predictive risk factors for DVT occurrence in the PT + TBI group. The incidence of PE within the whole population was 6.9% (59/847). Most patients with PE were in the PT + TBI group (64.4%, 38/59), and the PE rate was significantly higher in the PT + TBI group compared to the PT (p < 0.01) or TBI (p < 0.05) group. In conclusion, this study characterizes polytrauma patients at high risk for VTE occurrence and emphasizes that TBI markedly increases the incidence of DVT and PE in polytrauma patients. Delayed anticoagulant therapy and delayed mechanical prophylaxis were identified as the major risk factors for a higher incidence of VTE in polytrauma patients with TBI.

Multifactorial Shock: A Neglected Situation in Polytrauma Patients.

Background: Shock after traumatic injury is likely to be hypovolemic, but different types of shock (distributive shock, obstructive shock, or cardiogenic shock) can occur in combination, known as multifactorial shock. Multifactorial shock is a neglected area of study, and is only reported sporadically. Little is known about the incidence, characteristics, and outcomes of multifactorial shock after polytrauma. Methods: A retrospective, observational, multicenter study was conducted in four Level I trauma centers involving 1051 polytrauma patients from June 2020 to April 2022. Results: The mean Injury Severity Score (ISS) was 31.1, indicating a severely injured population. The most common type of shock in the early phase after polytrauma (≤48 h) is hypovolemic shock (83.2%), followed by distributive shock (14.4%), obstructive shock (8.7%), and cardiogenic shock (3.8%). In the middle phase after polytrauma (>48 h or ≤14 days), the most common type of shock is distributive shock (70.7%), followed by hypovolemic shock (27.2%), obstructive shock (9.9%), and cardiogenic shock (7.2%). Multifactorial shock accounted for 9.7% of the entire shock population in the early phase and 15.2% in the middle phase. In total, seven combinations of multifactorial shock were described. Patients with multifactorial shock have a significantly higher complication rate and mortality than those with single-factor shock. Conclusions: This study characterizes the incidence of various types of shock in different phases after polytrauma and emphasizes that different types of shock can occur simultaneously or sequentially in polytrauma patients. Multifactorial shock has a relatively high incidence and mortality in polytrauma patients, and trauma specialists should be alert to the possibility of their occurrence.

MIFNN: Molecular Information Feature Extraction and Fusion Deep Neural Network for Screening Potential Drugs.

Molecular property prediction is essential for drug screening and reducing the cost of drug discovery. Current approaches combined with deep learning for drug prediction have proven their viability. Based on the previous deep learning networks, we propose the Molecular Information Fusion Neural Network (MIFNN). The features of MIFNN are as follows: (1) we extracted directed molecular information using 1D-CNN and the Morgan fingerprint using 2D-CNN to obtain more comprehensive feature information; (2) we fused two molecular features from one-dimensional and two-dimensional space, and we used the directed message-passing method to reduce the repeated collection of information and improve efficiency; (3) we used a bidirectional long short-term memory and attention module to adjust the molecular feature information and improve classification accuracy; (4) we used the particle swarm optimization algorithm to improve the traditional support vector machine. We tested the performance of the model on eight publicly available datasets. In addition to comparing the overall classification capability with the baseline model, we conducted a series of ablation experiments to verify the optimization of different modules in the model. Compared with the baseline model, our model achieved a maximum improvement of 14% on the ToxCast dataset. The performance was very stable on most datasets. On the basis of the current experimental results, MIFNN performed better than previous models on the datasets applied in this paper.

The Efficacy of Nitrite Therapy for the Treatment of Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of nitrite therapy for the treatment of heart failure remains controversial. We conducted a systematic review and meta-analysis to explore the impact of nitrite therapy on heart failure. METHODS: We searched the PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through November 2019 for randomized controlled trials (RCTs) assessing the effect of nitrite therapy on heart failure. This meta-analysis was performed using the random-effect model. RESULTS: Three RCTs are included in the meta-analysis. Overall, compared with the control group for heart failure, nitrite therapy is associated with significantly reduced PCWP (Std. MD=-1.22; 95% CI=-1.81 to -0.63; P < 0.0001) and improved PAC (Std. MD=0.71; 95% CI=0.16 to 1.27; P = 0.01), but reveals no substantial influence on peak VO2 (Std. MD=-0.19; 95% CI=-0.49 to 0.11; P = 0.21), systolic BP (Std. MD=-3.98; 95% CI=-8.24 to 0.28; P = 0.07), mean BP (Std. MD=-1.53; 95% CI=-3.37 to 0.31; P = 0.10), or heart rate (Std. MD=0.40; 95% CI=-0.14 to 0.94; P = 0.15). CONCLUSIONS: Nitrite therapy may show some benefits to heart failure.

Clinical Efficacy and In Vitro Drug Sensitivity Test Results of Azithromycin Combined With Other Antimicrobial Therapies in the Treatment of MDR P. aeruginosa Ventilator-Associated Pneumonia.

Objective: The aim of the research was to study the effect of azithromycin (AZM) in the treatment of MDR P. aeruginosa VAP combined with other antimicrobial therapies. Methods: The clinical outcomes were retrospectively collected and analyzed to elucidate the efficacy of different combinations involving azithromycin in the treatment of MDR-PA VAP. The minimal inhibitory concentration (MIC) of five drugs was measured by the agar dilution method against 27 isolates of MDR-PA, alone or in combination. Results: The incidence of VAP has increased approximately to 10.4% (961/9245) in 5 years and 18.4% (177/961) caused by P. aeruginosa ranking fourth. A total of 151 cases of MDR P. aeruginosa were included in the clinical retrospective study. Clinical efficacy results are as follows: meropenem + azithromycin (MEM + AZM) was 69.2% (9/13), cefoperazone/sulbactam + azithromycin (SCF + AZM) was 60% (6/10), and the combination of three drugs containing AZM was 69.2% (9/13). The curative effect of meropenem + amikacin (MEM + AMK) was better than that of the meropenem + levofloxacin (MEM + LEV) group, p = 0.029 (p < 0.05). The curative effect of cefoperazone/sulbactam + amikacin (SCF + AMK) was better than that of the cefoperazone/sulbactam + levofloxacin (SCF + LEV) group, p = 0.025 (p < 0.05). There was no significant difference between combinations of two or three drugs containing AZM, p > 0.05 (p = 0.806). From the MIC results, the AMK single drug was already very sensitive to the selected strains. When MEM or SCF was combined with AZM, the sensitivity of them to strains can be significantly increased. When combined with MEM and AZM, the MIC50 and MIC90 of MEM decreased to 1 and 2 ug/mL from 8 to 32 ug/mL. When combined with SCF + AZM, the MIC50 of SCF decreased to 16 ug/mL, and the curve shifted obviously. However, for the combination of SCF + LEV + AZM, MIC50 and MIC90 could not achieve substantive changes. From the FIC index results, the main actions of MEM + AZM were additive effects, accounting for 72%; for the combination of SCF + AZM, the additive effect was 40%. The combination of AMK or LEV with AZM mainly showed unrelated effects, and the combination of three drugs could not improve the positive correlation between LEV and AZM. Conclusion: AZM may increase the effect of MEM or SCF against MDR P. aeruginosa VAP. Based on MEM or SCF combined with AMK or AZM, we can achieve a good effect in the treatment of MDR P. aeruginosa VAP.

Treatment of subclinical varicocele with acupuncture: A case report.

Varicocele is a vascular lesion characterized by abnormal dilatation and/or tortuosity of the veins of the pampiniform plexus, which sometimes manifests as chronic, dull pain in the scrotum, testicle or inguinal area. Subclinical varicocele (SCV) is as an early phase in the progression of its clinical analog. Given the lack of relevant studies on treatment strategies, no conclusive answer exists regarding how SCV should be managed. In this case report, a 40-year-old male patient visited our acupuncture outpatient clinic for left-sided scrotal pain and heaviness caused by SCV. After ten sessions of acupuncture treatments (acupuncture was performed at Zhongji (CV3), Guanyuan (CV4), qihai (CV6) and bilateral Guilai (ST29), Hegu (LI4), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), with electroacupuncture (EA) stimulation at Qihai (CV6) and Zhongji (CV3) as well as Guilai (ST29) on both sides), the patient was symptom-free. More unexpectedly, ultrasound reexamination showed no obvious abnormalities in bilateral spermatic veins. From this case, we conclude that acupuncture may be an effective alternative therapy for SCV treatment.

An optic-fiber graphene field effect transistor biosensor for the detection of single-stranded DNA.

Herein, a graphene field effect transistor (GFET) was constructed on an optic fiber end face to develop an integrated optical/electrical double read-out biosensor, which was used to detect target single-stranded DNA (tDNA). Two isolated Au electrodes were, respectively, prepared as the drain and source at the ends of an optic fiber and coated with a graphene film to construct a field effect transistor (FET). Probe aptamers modified with fluorophore 6'-carboxy-fluorescein (6'-FAM) were immobilized on the graphene for specific capture of tDNA. Graphene oxide (GO) was introduced to quench 6'-FAM and construct a fluorescence biosensor. Thus, a dual GFET and fluorescence biosensor was integrated on the end-face of an optic fiber. Following synchronous detection by fluorescence and FET methods, results showed satisfactory sensitivity for DNA detection. Compared with conventional biosensors using a single sensing technology, these dual sensing integrated biosensors significantly improved the reliability and accuracy of DNA detection. Furthermore, this proposed technique provides both a new biosensor for single-stranded DNA detection and a strategy for designing multi-sensing integrated biosensors.

Magnetic Graphene Field-Effect Transistor Biosensor for Single-Strand DNA Detection.

Herein, a magnetic graphene field-effect transistor biosensor was prepared through the transfer of a chemical vapor deposition graphene film onto a glass substrate to produce a sensing film and conductive channel. By fixing 1-pyrenebutanoic acid succinimidyl ester onto graphene film as an anchor, a probe aptamer was immobilized on the graphene film in order to capture magnetically labeled complementary single-stranded DNA. Our experiments showed that, within a periodic magnetic field, the biosensor impedance exhibited a periodic oscillation, the amplitude of which was correlated to the complementary DNA concentration. Based on this principle, the magnetic graphene field-effect transistor was utilized to detect single-stranded DNA with detection limition of 1 pM. The results were rationalized using a model wherein the magnetic force causes the DNA strand to bend, thereby resulting in magnetic nanobeads/DNA modulation of the double conductive layer of graphene transistors. Furthermore, since a periodic magnetic field could be introduced to produce a periodic impedance changes of MGFETs, sampling integration could be used to improve the signal-to-noise ratio efficiently by increasing the number of periods of the external magnetic field. Therefore, a novel biosensor for DNA detection with high sensitivity has been presented in this work. Based on the detection principle, this system may also be a potential tool for detecting other bio-molecules, cells, etc.

Acinetobacter baumannii Ventilator-Associated Pneumonia: Clinical Efficacy of Combined Antimicrobial Therapy and in vitro Drug Sensitivity Test Results.

Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth dilution methods determined the minimum inhibitory concentrations (MICs) of four antiseptic drugs singly used and combined two drugs against 36 isolates of multidrug-resistant (MDR) A. baumannii. Results: The incidence of VAP was approximately 6.9% (237/3424) between January 1, 2015 and December 31, and 35.9% (85/237) of the cases were caused by A. baumannii. Among these cases, 60 belonged to AB-VAP, for whom antimicrobial treatment plan was centralized and clinical data was complete. Moreover, all 60 strains of A. baumannii were MDR bacteria from reports microbiological laboratory. Resistance rate was lowest for amikacin (68.3%) and ampicillin sulbactam (71.7%). Resistance rate for imipenem increased from 63.2 to 90.9% during the 3 years. However, in these 60 cases of AB-VAP, the combination between 4 antibiotics was effective in most cases: the effective rate was 75% (18/24) for sulbactam combined with etilmicin, 71.4% (10/14) for sulbactam combined with levofloxacin, 72.7% (8/11) for meropenem combined with etilmicin, and 63.6% (7/11) for meropenem combined with levofloxacin. There was no statistical difference between four regimens (P > 0.05). Sulbactam combined with etilmicin decreased 1/2 of MIC50 and MIC90 of sulbactam while the decreases in etilmicin were more obviously than single drug. When adopting meropenem combined with levofloxacin or etilmicin, the MIC of meropenem reduced to 1/2 of that in applying single drug. As for sulbactam or meropenem combined with levofloxacin, it also lessened the MIC50 of levofloxacin to 1/2 of that for single drug. FIC results suggested that the effects of four combined antimicrobial regimens were additive or unrelated. When sulbactam was combined with etimicin, the additive effect was 63.89%. Conclusion: Drug combination sensitivity test in vitro may be helpful for choosing antimicrobial treatment plans. Sulbactam or meropenem as the basis of treatment regimens can function as the alternatives against AB-VAP. Sulbactam combined with etimicin has been regarded as a recommended regimen in Suizhou, Hubei, China.

Meropenem and Amikacin for Management of Post-Neurosurgical Infections from Acinetobacter baumannii.

Background: Intra-cranial infection with Acinetobacter baumannii is a tough problem because of the presence of multi-resistance and poor drug penetration through the blood-brain barrier. Such intra-cranial infections can lead to serious complications and death. We retrospectively analyzed the culture results and clinical characteristics of patients with intra-cranial infections in our hospital and suggested intravenous (IV) meropenem and intra-thecal (IT) amikacin therapy may be effective in the management of A. baumannii infection. Case presentation: We reported four cases of post-neuro-surgical A. baumannii intra-cranial infection whose clinical futures were high fever and consciousness disturbance. Our patients were treated successfully with IV meropenem and IT amikacin. Conclusion: We presented our cases of pandrug-resistant A. baumannii intra-cranial infection that was managed successfully with a systemic provision of IV meropenem and IT amikacin. Therefore, these cases exemplify that systemic administration of IV meropenem and IT amikacin can be a good therapeutic option against A. baumannii intra-cranial infection when colistin is not available.

Sterilization Effects of Adult-targeted Baits Containing Insect Growth Regulators on Delia antiqua.

The onion maggot, Delia antiqua, is a devastating pest of liliaceous crops and current control measures fail to avert pesticide residues, threats to agroecosystem, and costly expenditures. Insect growth regulators (IGRs) are used as trypetid pest chemosterilants for their suppression on adult fertility and fecundity, but their effects on onion flies are unknown. Here, three IGRs (lufenuron, cyromazine, pyriproxyfen) were incorporated into baits to evaluate their effects on onion fly survival, fecundity, fertility, susceptibility of adults in different ages and offspring development. Lufenuron and cyromazine did not affect survival of new-emerged adults, but lufenuron inhibited adult fertility without affecting fecundity, and cyromazine reduced fertility and fecundity. Differently, pyriproxyfen enhanced fecundity within 10 days after treatment, while it reduced adult survival without affecting fertility. The fertility of younger adults was affected by lufenuron and cyromazine whereas the fecundity was affected with cyromazine and pyriproxyfen. For offspring of onion flies treated with lufenuron or cyromazine, most of larvae died within 5 days after hatch, but surviving larvae pupated and emerged normally. Pyriproxyfen did not affect offspring larval survival or pupation but affected pupal emergence. Thus, lufenuron and cyromazine could be potential chemosterilants for onion flies.

Discovery of 6-deoxydapagliflozin as a highly potent sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

Systematic mono-deoxylation of the four hydroxyl groups in the glucose moiety in dapagliflozin led to the discovery of 6-deoxydapagliflozin 1 as a more active sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 0.67 nM against human SGLT2 (hSGLT2) vs 1.16 nM for dapagliflozin). It exhibited more potent blood glucose inhibitory activity in rat oral glucose tolerance test and induced more urinary glucose in rat urinary glucose excretion test than its parent compound dapagliflozin.