P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy.

Sepsis is defined as a dysregulated host response to infection resulting in life-threatening organ dysfunction. Sepsis-associated encephalopathy (SAE) is the main manifestation of sepsis. Inflammation, peroxidation stress injury, and apoptosis are the main factors involved in the pathogenesis of SAE. A growing body of evidence has proved that P2X7 receptor (P2X7R), a cationic channel receptor that is widely distributed in the body, plays a major role in the occurrence and development of inflammatory injury. Therefore, this review mainly describes the activation of P2X7R in sepsis, which leads to the recruitment of inflammatory cells to the cerebral vasculature, the destruction of the blood-brain barrier, the activation of microglial cells in the brain, the apoptosis of brain cells, and other damage processes. This review also illustrates the potential therapeutic value of P2X7R inhibition in SAE.

Neuromorphic Computing of Optoelectronic Artificial BFCO/AZO Heterostructure Memristors Synapses.

Compared with purely electrical neuromorphic devices, those stimulated by optical signals have gained increasing attention due to their realistic sensory simulation. In this work, an optoelectronic neuromorphic device based on a photoelectric memristor with a Bi2FeCrO6/Al-doped ZnO (BFCO/AZO) heterostructure is fabricated that can respond to both electrical and optical signals and successfully simulate a variety of synaptic behaviors, such as STP, LTP, and PPF. In addition, the photomemory mechanism was identified by analyzing the energy band structures of AZO and BFCO. A convolutional neural network (CNN) architecture for pattern classification at the Mixed National Institute of Standards and Technology (MNIST) was used and improved the recognition accuracy of the MNIST and Fashion-MNIST datasets to 95.21% and 74.19%, respectively, by implementing an improved stochastic adaptive algorithm. These results provide a feasible approach for future implementation of optoelectronic synapses.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

[Review of Comprehensive Evaluation System of Vehicle Pollution and Carbon Synergistic Reduction].

Vehicle emissions have become one of the most important air pollution sources in China. Promoting vehicle synergistic reduction of pollution and carbon is the key to improving regional environmental quality and achieving the carbon peaking and carbon neutrality goals. Building a collaborative evaluation system and comprehensive quantitative method is an important prerequisite for scientific and effective implementation of vehicle pollution and carbon synergistic reduction. Therefore, it is significant to extensively review existing synergistic evaluation methods and comprehensive environmental benefit accounting methods of atmospheric pollution and carbon reduction. On this basis, we focused on vehicle emission characteristics, systematically organized the key indicators of vehicle collaborative reduction evaluation, and summarized quantitative methods of policy effects from three aspects (health exposure cost, climate change cost, and pollutant control cost), to provide theoretical support for policy formulation, schemes selection, and their effect evaluation. For the future, the assessment of vehicle coordinated emission reduction is proposed to accelerate unified index system establishment, deeply analyze the spatial distribution of environmental benefits, focus on the pollution transfer caused by vehicle electrification, and explore the quantitative methods of climate change cost due to extreme weather.

Microscopic mechanisms of pressure-induced amorphous-amorphous transitions and crystallisation in silicon.

Some low-coordination materials, including water, silica, and silicon, exhibit polyamorphism, having multiple amorphous forms. However, the microscopic mechanism and kinetic pathway of amorphous-amorphous transition (AAT) remain largely unknown. Here, we use a state-of-the-art machine-learning potential and local structural analysis to investigate the microscopic kinetics of AAT in silicon after a rapid pressure change. We find that the transition from low-density-amorphous (LDA) to high-density-amorphous (HDA) occurs through nucleation and growth, resulting in non-spherical interfaces that underscore the mechanical nature of AAT. In contrast, the reverse transition occurs through spinodal decomposition. Further pressurisation transforms LDA into very-high-density amorphous (VHDA), with HDA serving as an intermediate state. Notably, the final amorphous states are inherently unstable, transitioning into crystals. Our findings demonstrate that AAT and crystallisation are driven by joint thermodynamic and mechanical instabilities, assisted by preordering, occurring without diffusion. This unique mechanical and diffusion-less nature distinguishes AAT from liquid-liquid transitions.

Space-time mapping on the sagittal axis in congenital blindness.

Previous evolutionary perspectives proposed that the space-time mapping on the sagittal axis originates from visuo-locomotion coupling when walking/running forward. Accordingly, the congenitally blind could not have developed a sagittal mental timeline if the latter depends on such a visuo-locomotion coupling. However, this conclusion was reached in only a single empirical study (Rinaldi et al. in J Exp Psychol General 147:444-450, 2018), and its theoretical underpinnings are not entirely convincing as locally static and continuous auditory input undergoes a relatively similar change as function of self-locomotion, but this type of sensory-locomotion coupling is spared even in congenital blindness. Therefore, the present study systematically explored whether the congenitally blind show space-time mappings on the sagittal axis using different paradigms in three experiments. In Experiment 1, using a typical implicit RT task, the congenitally blind showed the same preferred space-time mapping in the sagittal dimension as normally sighted participants did. In Experiment 2, this space-time mapping occurred even automatically when temporal relations were task-irrelevant in a naming task. In Experiment 3, in an explicit space-time mapping task, the congenitally blind were more likely to locate the past behind and the future in front of their bodies. Moreover, most blind participants used spatial metaphors for their space-time mapping on the sagittal axis. These results supported the conclusion that the congenitally blind have a sagittal mental timeline, and that their sensory-locomotion coupling experience was either more similar to that of sighted participants or not critical for the space-time mapping. The present study, thus, also helps to clarify the origin of the sagittal mental timeline.

Menaquinone-4 exerts a protective effect against carbon tetrachloride-induced acute liver injury in mice by alleviating ferroptosis / 临床肝胆病杂志

ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.

Hemoglobin levels and clinical outcomes after extracorporeal circulation auxiliary to open heart surgery: a retrospective cohort study.

BACKGROUND: Extracorporeal circulation auxiliary to open heart surgery is a common procedure used to treat heart diseases. However, the optimal transfusion strategy for patients undergoing this surgery remains a subject of debate. This study aims to investigate the association between hemoglobin levels and clinical outcomes in patients undergoing extracorporeal circulation auxiliary to open heart surgery, with the ultimate goal of improving surgical success rates and enhancing patients' quality of life. METHODS: A retrospective analysis was conducted on data from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database, including 4144 patients. The patients were categorized into five groups based on their minimum hemoglobin levels during hospitalization. Baseline characteristics, clinical scores, laboratory results, and clinical outcome data were collected. Statistical analyses utilized descriptive statistics, ANOVA or Kruskal-Wallis tests, Kaplan-Meier method, and Log-rank test. RESULTS: The results revealed a significant correlation between hemoglobin levels and in-hospital mortality, as well as mortality rates at 30 days, 60 days, and 180 days (p < 0.001). Patients with lower hemoglobin levels exhibited higher mortality rates. However, once hemoglobin levels exceeded 7g/dL, no significant difference in mortality rates was observed (p = 0.557). Additionally, lower hemoglobin levels were associated with prolonged hospital stay, ICU admission time, and mechanical ventilation time (p < 0.001). Furthermore, hemoglobin levels were significantly correlated with complication risk, norepinephrine dosage, and red blood cell transfusion volume (p < 0.001). However, there was no significant difference among the groups in terms of major complications, specifically sepsis (p > 0.05). CONCLUSION: The study highlights the importance of managing hemoglobin levels in patients undergoing heart surgery with extracorporeal circulation. Hemoglobin levels can serve as valuable indicators for predicting clinical outcomes and guiding treatment decisions. Physicians should carefully consider hemoglobin levels to optimize transfusion strategies and improve postoperative patient outcomes. Further research and intervention studies are warranted to validate and implement these findings in clinical practice.

Does walking/running experience shape the sagittal mental time line?

A growing body of evidence suggested that time could be separately represented either on the lateral or sagittal axis. And the lateral mental time line has an origin associated with sensorimotor experience, e.g., reading/writing. However, it is still not clear whether the sagittal mental time line also originates from sensorimotor experience, e.g., walking/running. To address this question, we examined how the movement experience affected the space-time mapping on the lateral and sagittal axes using the virtual reality technique in two experiments. The results showed that the virtual movement experience had significant effects on the space-time mapping on the lateral axis (Experiment 1), but not on the sagittal axis (Experiment 2). This finding supported that the space-time mapping on the lateral axis does originate from sensorimotor experience, while the space-time mapping on the sagittal axis more likely originates from spatial metaphors in languages or other cultural experiences.

Multidrug-Resistant Organism Infections of Inpatients in a Hospital in Eastern China from 2015 to 2021.

Background: The prevalence of multidrug-resistant organisms (MDRO) is gradually increasing in the global scope, causing serious burden to patients and society, which is an important public health problem. Objective: To analyze the distribution and trend of MDROs and provide a reference for hospital infection control. Methods: Collected data on MDROs infections among inpatients in a Grade III Level A hospital in Suzhou from 2015 to 2021, including drug-resistant bacteria strains and specimen sources, etc. Mantel-Haenszel χ2 test was used to evaluate the trend of infection rates over the years and SPSS version 26.0 was used for statistics analysis. Results: The hospital infection rate showed an overall downward trend across the seven-year period, ranging from 1.53% to 2.10%. According to the analysis of change of drug-resistant bacteria strains, the highest infection rate was carbapenem-resistant Acinetobacter baumannii (CRABA) (63.74%), followed by methicillin-resistant Staphylococcus aureus (MRSA) (46.37%), carbapenem-resistant Pseudomonas aeruginosa (CRPAE) (24.87%), carbapenem-resistant Enterobacteriaceae (CRE) (13.14%) and vancomycin-resistant Enterococcus (VRE) (0.42%). The results of Mantel-Haenszel χ2 test showed that there was a linear relationship between the detection rate of CRE and CRPAE and the time (P<0.001), but the correlation was not strong (R = 0.136; R = 0.139). The overall detection rate of the five pathogens also increased (P<0.001). The majority of the specimens, mainly from sputum, airway secretions, and midstream urine, had a detection rate of over 70%. Conclusion: Our data showed that the detection rate of MDROs generally increased from 2015 to 2021, although the hospital infection rate displayed a declining trend. Among the detection rate MDROs, the highest was CRABA, and the lowest was VRE. It is necessary to enhance the prevention, control, and management of MDROs infections in the clinical practice.

Role of Guanxi (interpersonal relationship) in bribe-taking behaviors: evidence from China.

Bribery, an illegal conspiracy between two transactional parties, has a wide range of destructive effects on society. From an interpersonal interaction perspective, we explored how Guanxi (interpersonal relationships, including direct and indirect ones) influences individuals, especially government officials' bribe-taking probability, using behavioral experiments and questionnaires. The findings suggested that direct Guanxi promoted individuals' acceptance of bribes (Study 1a), and indirect Guanxi had the same role and effect sizes (Study 1b). However, the mechanisms were slightly different. Government officials were more likely to accept bribes from family members and friends (direct Guanxi) (than strangers) because they had more trust and felt more responsible and obligated to help them (Study 2). However, accepting bribes from those who contacted them through their family or friends (indirect Guanxi) (vs. strangers) was only driven by trust (Study 3). The present study explores the lubricant role of Guanxi in corruption, extends the literature on why bribery occurs from a new perspective, and provides suggestions for fighting corruption.

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model.

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1ß production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk-/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.

The efficiency of quantum teleportation with three-qubit entangled state in a noisy environment.

Quantum teleportation plays a significant role in the field of quantum communication. This paper investigates quantum teleportation through a noisy environment by using GHZ state and non-standard W state as quantum channels. We analyze the efficiency of quantum teleportation by solving analytically a master equation in Lindblad form. Following the quantum teleportation protocol, we obtain the fidelity of quantum teleportation as a function of evolution time. The calculation results show that the teleportation fidelity using non-standard W is higher in comparison to GHZ state at the same evolution time. Moreover, we consider the efficiency of teleportation with weak measurements and reverse quantum measurement under amplitude damping noise. Our analysis suggests that the teleportation fidelity using non-standard W is also more robust to noise than GHZ state in the same conditions. Interestingly, we found that weak measurement and its reverse operation have no positive effect on the efficiency of quantum teleportation by using GHZ and non-standard W state in the amplitude damping noise environment. In addition, we also demonstrate the efficiency of quantum teleportation can be improved by making minor modifications to the protocol.

[Railway Emission Trends in China Based on Fuel Life Cycle Analysis].

Railway transportation is one of the main modes of modern transportation. Under the dual constraints of air quality improvement and carbon neutrality achievement, clarifying the emission trend of CO2 and pollutants in railway transportation is of great significance for pollution and carbon reduction in the transport sector. In this study, the CO2 and pollutant emission characteristics of Chinese railways from 2001 to 2018 were analyzed based on the fuel life cycle method. Then, railway emission trends from 2019-2030 were assessed combined with scenario analysis. The results showed that with the advancement of railway electrification, the use of new diesel locomotives, and the continuous upgrading of fuel standards, the total CO2 and pollutant emissions in the fuel life cycle of railway transportation showed an upward and downward trend, respectively. In 2018, the total emissions of CO2, NOx, CO, BC, and SOx from railway transportation were 3780.29×104t, 11.98×104t, 3.94×104t, 0.20×104t, and 3.08×104t, respectively. Accelerating the improvement of power structure and reducing unit energy consumption were the best single control strategies to reduce railway emissions of CO2, SOx, NOx, BC, and CO, respectively. Under the comprehensive scenario of actively responding to railway pollution and carbon reduction, the emission reduction rates of CO2, NOx, CO, BC, and SOx could reach 35%, 37%, 39%, 32%, and 45%, respectively. The stagnation of power structure reform or the railway electrification process will lead to a significant increase in total emissions of railway transportation. Therefore, the pollution and carbon reduction of railway transportation requires continuous attention.

CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Buyang Huanwu Decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury / 中国结合医学杂志

OBJECTIVE@#To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP).@*METHODS@#The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining.@*RESULTS@#The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01).@*CONCLUSIONS@#BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.

Microbial transformation of artemisinin and its derivatives / 中国中药杂志

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the pre-shock state on the mortality of patients with sepsis.@*METHODS@#We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.@*RESULTS@#A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.@*CONCLUSION@#The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Value of three hemolysis tests and carboxyhemoglobin in the diagnosis of hemolytic disease of the fetus and newborn / 中国输血杂志

【Objective】 To investigate the value of three hemolysis tests and carboxyhemoglobin (COHb) level in the diagnosis of hemolytic disease of the fetus and newborn (HDFN). 【Methods】 From January 1, 2019 to December 31, 2022, the neonates hospitalized in the Department of Neonatology of Hebei Provincial Children's Hospital with suspected hemolytic disease who had serological testing were retrospectively enrolled in the study. They were distributed into HDFN group and non-HDFN group according to the final diagnosis. Their clinical and laboratory data were collected and analyzed, and the COHb level was detected by blood gas analyzer. 【Results】 A total of 378 neonates with HDFN and 217 neonates without HDFN were included in the study. Most of the neonates in HDFN group were full-term infants (348/378, 92.1%), with median gestational age of 39.1 (38.3, 40.0) weeks. Three hundred and fifty-four cases (354/378, 93.7%) were ABO-HDFN and the rest were Rh HDFN. There were significant differences in the level of serum total bilirubin, hemoglobin, COHb and reticulocyte percentage at admission between the two groups(P<0.05). The positive rate of three hemolysis tests in HDFN group decreased with the increase of the days after birth. The highest positive rate (more than 80%) was observed within 2 days after birth. Correlation analysis showed a negative relationship between the COHb level and the age (rs = -0.434, P<0.001) . Among the three hemolysis tests in HDFN group, the positive rate of antibody release test was the highest (69.0%), followed by the free antibody test (55.6%) and the direct antiglobulin test (DAT) (36.0%). Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value of COHb was 1.15%.The sensitivity of COHb ≥ 1.15% was 51.8%, higher than single DAT (36.0%) . The diagnosis effectiveness of three hemolysis tests couldn't be improved when combined with COHb detection(Z = -0.727, P>0.05) . 【Conclusion】 The three hemolysis tests are important in the diagnosis of HDFN, among which the antibody release test has the highest sensitivity. COHb has certain value for the diagnosis of HDFN, but joint testing cannot improve the diagnosis effectiveness of three hemolysis tests. Hemolysis tests and/or COHb detection should be conducted for neonates at risk of hemolysis as early as possible after birth.