Automatic wound closure system: closure of large wounds by stretching the skin around the wound.

Large-wound treatment often requires autologous skin grafting or skin flap transfer, causing iatrogenic secondary injuries. Thus, we have developed an automatic wound closure system that consists of a stretch module, microcontroller, and touch screen. Full-thickness wounds (8 × 14 cm) on Bama miniature pigs were manually closed by direct suture in control animals and with three different tension levels performed by the automatic device in the experimental animals. Wound-closure conditions, post-closure healing, and scars were evaluated. Post-operative microscopic changes in collagen fibers, local cell apoptosis, and changes in vascular density were compared between the two wound-closure techniques. In the control group and the first experimental group, which used a traction force of 15 N, primary wound closure could not be achieved. The other two experimental groups used a traction force of 30 N and 60 N and all wounds achieved primary closure. Collagen-fiber stretching was observed histologically in all groups and collagen-fiber breakdown occurred in some wounds when the traction force was 60 N. Scar hyperplasia was significantly reduced in the automatic wound closure system groups. The collagen content decreased, cell apoptosis increased, and vascular density decreased in local tissues in the early post-closure stage, but eventually recovered to normal-skin levels. In summary, we developed an automatic wound closure system that effectively and safely stretches dermal-collagen fibers under an appropriate traction force (30 N) and stretch wound-peripheral skin to cover the wound, achieve primary closure, and reduce scar hyperplasia.

Pyroptosis and mitochondrial function participated in miR-654-3p-protected against myocardial infarction.

Myocardial infarction (MI) is one of the leading causes of heart failure with highly complicated pathogeneses. miR-654-3p has been recognized as a pivotal regulator of controlling cell survival. However, the function of miR-654-3p in cardiomyocytes and MI has yet to be reported. This study aimed to identify the role of miR-654-3p in the regulation of myocardial infarction. To understand the contribution of miR-654-3p on heart function, we generated cardiac-specific knockdown and overexpression mice using AAV9 technology in MI injury. Mechanically, we combined cellular and molecular techniques, pharmaceutical treatment, RNA sequencing, and functional testing to elucidate the potential pathological mechanisms. We identified that mice subjected to MI decreased the expression of miR-654-3p in the border and infarcted area. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. Furthermore, we found a deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death but not other programmed cell death. Intriguingly, miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Cardiac elevating miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Using RNA sequence and molecular biological approaches, we found overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function. Our finding identified the character of miR-654-3p in protecting against MI damage by mediating pyroptosis and mitochondrial metabolism. These findings provide a new mechanism for miR-654-3p involvement in the pathogenesis of MI and reveal novel therapeutic targets. miR-654-3p expression was decreased after MI. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. The deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death. miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Overexpression of miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function.

The evolving role of social media in enhancing quality of life: a global perspective across 10 countries.

BACKGROUND: Excessive or inappropriate use of social media has been linked to disruptions in regular work, well-being, mental health, and overall reduction of quality of life. However, a limited number of studies documenting the impact of social media on health-related quality of life (HRQoL) are available globally. AIM: This study aimed to explore the perceived social media needs and their impact on the quality of life among the adult population of various selected countries. METHODOLOGY: A cross-sectional, quantitative design and analytical study utilized an online survey disseminated from November to December 2021. RESULTS: A total of 6689 respondents from ten countries participated in the study. The largest number of respondents was from Malaysia (23.9%), followed by Bangladesh (15.5%), Georgia (14.8%), and Turkey (12.2%). The prevalence of social media users was over 90% in Austria, Georgia, Myanmar, Nigeria, and the Philippines. The majority of social media users were from the 18-24 age group. Multiple regression analysis showed that higher education level was positively correlated with all four domains of WHOQoL. In addition, the psychological health domain of quality of life was positively associated in all countries. Predictors among Social Media Needs, Affective Needs (ß = -0.07), and Social Integrative Needs (ß = 0.09) were significantly associated with psychological health. CONCLUSION: The study illuminates the positive correlation between higher education levels and improved life quality among social media users, highlighting an opportunity for policymakers to craft education-focused initiatives that enhance well-being. The findings call for strategic interventions to safeguard the mental health of the global social media populace, particularly those at educational and health disadvantages.

Iron overload in anaemia with underlying haemoglobin constant spring in an antenatal mother in primary care.

This is the case of a gravida 3 para 1 woman in her late 20s with underlying haemoglobin constant spring who visited a healthcare clinic for an antenatal check-up. Towards the end of her second trimester, she experienced lethargy. During her antenatal booking, she was diagnosed with mild asymptomatic anaemia, high serum ferritin, T saturation of 88% and abnormal liver function tests. She was referred to a hospital where an MRI scan revealed over 2 g of iron deposits in her liver, leading to a revised diagnosis of iron overload. Treatment included deferoxamine and expectant management throughout her antenatal period, and her delivery was uncomplicated. While iron deficiency anaemia is common in pregnancy, it is crucial not to overlook iron deposition and the distinction from acute fatty liver during pregnancy to prevent treatment delays.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Clinical effects of Bufei Huatan Dingchuan Decoction on patients with acute exacerbation of chronic obstructive pulmonary disease of Lung-Kidney Deficiency Pattern / 中成药

AIM To explore the clinical effects of Bufei Huatan Dingchuan Decoction on patients with acute exacerbation of chronic obstructive pulmonary disease of Lung-Kidney Deficiency Pattern.METHODS One hundred and thirty-eight patients were randomly assigned into control group(69 cases)for 4-week intervention of conventional treatment,and observation group(69 cases)for 4-week intervention of both Bufei Huatan Dingchuan Decoction and conventional treatment.The changes in clinical effects,MMP-2,HIF-1α,TGF-β1,Gal-3,IL-6,pulmonary function indices(FVC,PEF,FEV1/FVC),6-minute walk distance,CAT score and TCM syndrome score were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased MMP-2,HIF-1α,TGF-β1,IL-6,Gal-3,CAT score,TCM syndrome score(P＜0.05),increased function indices(except for FVC)(P＜0.05),and prolonged 6-minute walk distance(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients of Lung-Kidney Deficiency Pattern,Bufei Huatan Dingchuan Decoction can alleviate inflammatory reactions,improve body hypoxia state,regulate lung functions,prevent airway tissue remodeling,promote disease recovery,and enhance clinical effects.

A new pyrazine from Hypecoum erectum L / 药学学报

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

A new suberin from roots of Ephedra sinica Stapf / 药学学报

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.

Minimally invasive percutaneous screw internal fixation under robot navigation for the treatment of a hamate bone fracture.

PURPOSE: Hamate fractures are rare fractures of the wrist and there is still no consensus on the optimal treatment for these fractures, especially hook of hamate fractures. Herein, the authors present a case study of a series of patients who were treated with closed reduction and minimally invasive percutaneous fixation under robot navigation. METHODS: This retrospective study reviewed 14 patients who had nondisplaced or minimally displaced hamate fractures on computerized tomography images and were treated using the treatment in our centre from November 1, 2019, to October 31, 2022. At the final follow-up, the flexion-extension and radial-ulnar range of motion of the wrist were measured, and the grip strength and pinch strength were measured. The pain of the wrist was assessed using the visual analogue scale (VAS). The Mayo wrist score reflected the recovery of the wrist. RESULTS: The mean total operative duration was 40.1 min. All the fractures showed union at a mean of 3.0 months. At a mean follow-up of 23.3 months (range 6-36 months), the mean VAS score was 0.7, the average Mayo wrist score was 95, and the mean pinch strength and grip strength were 11.3 and 38.7 kg, respectively. The flexion-extension arc was 138.3°, the mean radial and ulnar deviation arc was 63.8°, and the mean pronation-supination arc was 172.3°. And the time of return to the original occupation was mean 4 months (3~6 months). There were no complications, such as infection or nerve paralysis. CONCLUSIONS: This study suggests that nondisplaced or minimally displaced hamate hook fractures can be successfully treated by closed reduction and internal fixation with a headless compression screw with the assistance of robot navigation, and the small fragment of fracture can be accurately fixed with minimal iatrogenic injury.

[Separation, characterization, and antiviral activity of colloidal phase state of Maxing Shigan Decoction].

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.

Factors influencing parents' hesitancy to vaccinate their children aged 5-11 years old against COVID-19: results from a cross-sectional study in Malaysia.

Introduction: Vaccination programs have been rolled out across the globe to contain and mitigate the spread of the COVID-19 infection. Until recently, such programs were limited to adults and the older population, thereby limiting children from getting vaccinated. Recently, the Malaysian government rolled out vaccination for children aged 5-11 years. However, there are certain factors that might affect vaccination uptake among children. This study explores factors influencing parents' hesitancy to vaccinate children in Malaysia. Method: A nationwide online cross-sectional convenience sampling survey from April 21, 2022 to June 3, 2022 was conducted. The study used descriptive statistics to inform about vaccine hesitancy among parents. Cross-tabulation was performed to calculate the frequency and percentage of vaccine hesitancy, quality of life, e-health literacy, and the 5C psychological antecedents of vaccination among parents with children 5-11 years in Malaysia. Graphical methods were used to portray the levels of e-health literacy and levels of 5C psychological antecedents of vaccination. The study used both bi-variate and multivariate analysis to understand the relationship between vaccine hesitancy and the socio-demo-economic factors, quality of life, e-health literacy and 5C psychological antecedents. Results: Of 382 participants, almost one-third (33%) of participants reported vaccine hesitancy for their children. For 5C's psychological antecedents of vaccination, around one quarter (26.96%) reported disagreement for confidence in vaccination, almost half (52.36%) reported disagreement for vaccination complacency, three-fifths (60.99%) reported vaccination constraint, one quarter (25.92%) reported calculation antecedent, and almost one-third reported disagreement over collective responsibility antecedent (25.92%). Chi-square test revealed that gender, employment status, and parents' COVID-19 vaccination status were significantly associated (p<0.05) with vaccine hesitancy among parents. Assessing the influence of transactional e-health literacy, only the communication component contained a significant association (p<0.05). Among the 5C psychological antecedents, confidence, calculation, and collective responsibility were significantly associated (p<0.05) with vaccine hesitancy. Parents with secondary [OR: 8.80; CI: 2.44-31.79, (p<0.05)], post-secondary [OR: 5.21; CI: 2.10-13.41, (p<0.05)], and tertiary education [OR: 6.77; CI: 2.25-20.35, (p<0.05)] had significantly higher likelihood of vaccine hesitancy than those with primary education. Conclusion: Highly educated parents are more skeptical and are more likely to perceive the vaccine as unsafe and ineffective for their children. It is critical to disseminate the required information about the vaccine safety to the educated group.

Prognostic significance of TMEM131L in glioma and establishment of oxidative stress prognostic model.

Gliomas are the most aggressive of all brain tumors. In this study, it was found that there is a significant expression of transmembrane-like 131 (TMEM131L) in glioma tissues. The relevance of TMEM131L in the diagnosis and clinical prognosis of GBM and LGG was verified by additional clinical correlation and survival analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve reflected the diagnostic effect of TMEM131L on the clinicopathologic features of glioma. As a unique molecular marker for the poor prognosis of overall survival (OS), PFI, and DSS in patients with GCB and LGG, TMEM131L might be employed, according to time-dependent ROC curves and Kaplan-Meier survival analysis at 1, 3, and 5 years. The potential methylation sites of TMEM131L were selected by correlation analysis between TMEM131L and DNA methylation sites. Meanwhile, TMEM131L was significantly correlated with matrix, immunity, and estimated scores of GBM and LGG. The CIBERSORT analysis revealed a significant correlation between immune checkpoint and infiltration of 22 different kinds of immune cells. Coexpression genes of TMEM131L associated with oxidative stress phenotype were screened by the LASSO logistic regression analysis. Nomogram and calibration curves further confirmed that the prognostic model composed of SYT1, CREB3L3, ITPR1, RASGRF2, PDX1, and RASGRF1 has good stability and potential application value for poor prognosis in patients with glioma.

The incremental significance of heart rate recovery as a predictor during exercise-stress myocardial perfusion SPECT imaging in individuals with suspected coronary artery disease.

Background: Major adverse cardiac events (MACE) are more likely to occur when abnormal heart rate recovery (HRR). This study aimed to assess the incremental predictive significance of HRR over exercise stress myocardial perfusion single-photon emission computed tomography (MPS) results for MACE in individuals with suspected coronary artery disease (CAD). Methods: Between January 2014 and December 2017, we continually gathered data on 595 patients with suspected CAD who received cycling exercise stress MPS. HRR at 1, 2, 3, and 4 min were used as study variables to obtain the optimal cut-off values of HRR for MACE. The difference between the peak heart rate achieved during exercise and the heart rate at 1, 2, 3, and 4 min was used to calculate the HRR, as shown in HRR3. Heart rate variations between two locations in time, such as HRR2 min-1 min, were used to establish the slope of HRR. All patients were followed for a minimum of 4 years, with MACE as the follow-up goal. The associations between HRR and MACE were assessed using Cox proportional hazards analyses. Results: Patients with MACE were older (P = 0.001), and they also had higher rates of hypertension, dyslipidemia, diabetes, abnormal MPS findings (SSS ≥ 5%), medication history (all P < 0.001), and lower HRR values (all P < 0.01). Patients with and without MACE did not significantly vary in their HRR4 min-3 min. The optimal cut-off of HRR1, 2, and 3 combined with SSS can stratify the risk of MACE in people with suspected CAD (all P < 0.001). HRR 1, 2, and 3 and its slope were linked to MACE in multivariate analysis, where HRR3 was the most significant risk predictor. With a global X2 increase from 101 to 126 (P < 0.0001), HRR3 demonstrated the greatest improvement in the model's predictive capacity, incorporating clinical data and MPS outcomes. Conclusions: HRR at 3 min has a more excellent incremental prognostic value for predicting MACE in patients with suspected CAD following cycling exercise stress MPS. Therefore, incorporating HRR at 3 min into known predictive models may further improve the risk stratification of the patients.

Experimental Study and Modelling of Fresh Behaviours of Basalt Fibre-Reinforced Mortar Based on Average Water Film Thickness and Fibre Factor.

Though previous studies have indicated that the fresh behaviours of plain mortar/concrete are mainly governed by the average water film thickness (AWFT), whether the concept of AWFT is also applicable to fibrous mortar/concrete still needs to be explored. Furthermore, for fibrous mortar/concrete, it is obvious that the fibres added also have certain effects on the fresh behaviours. In two previous studies on basalt fibre-reinforced mortar (BFRM), the integral effects of the AWFT and fibre dosage as well as the integral effects of the AWFT and fibre length were individually investigated. In this study, a fibre factor (FF) defined as the fibre volume multiplied by the fibre aspect ratio was employed and 24 extra mortar groups were tested. A total of 68 mortar groups were applied in numerical analysis. The results of the regression analysis yielded good correlations of the workability, fluidity, cohesiveness, and adhesiveness of BFRM with the AWFT and FF, suggesting that the AWFT and FF are together the governing parameters controlling the fresh behaviours of BFRM. Hence, the AWFT and FF may be used to develop a model for the fresh properties of BFRM.

Implementation of peer-support services in Asia: A scoping review.

WHAT IS KNOWN ON THE SUBJECT: Peer-support services was started in the 1970s psychiatric survivor movement in the United States of America (USA) due to the lack of transitional support for deinstitutionalized psychiatric patients. Delivered by peer-support workers (PSWs) with lived experiences of mental health conditions, peer-support workers use their experiential knowledge to help others with similar conditions. The paradigm shifts in mental health recovery has led to an increase in interest on peer-support services among the Asia countries. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The diversity political and cultural differences in Asia makes it a unique for people to understand the mental health ecosystem that exist within. This review is timely as it provides the insights into the current state of peer-support services for mental health consumers in Asia and the future research on them. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: First, this review provided a broad overview on the current types of peer-support services and their implementation in Asia. Second, emphasized the importance and value of peer-support services for individuals with mental health conditions in their journey towards recovery. Third, important to build a more positive image for peer-support workers by assigning more clarity to their roles and systematizing training to hone their skills in providing peer support. ABSTRACT: Introduction The increasing recognition and need for recovery-oriented services led to the heightened interests of peer-support services globally, including Asia. However, little is known about the peer-support services in Asia as compared to the West, where peer-support services primarily originated from and are well established. Aim To examine available evidence on the implementation of peer-support services for such consumers in Asia. Method This scoping review was based on the Arksey & O'Malley's framework. A comprehensive search was performed across seven electronic databases. The grey literature was also searched through Open Grey and ProQuest Dissertation and Theses, alongside hand searching of the reference of the studies. Articles searched was from January 2000 to December 2021. Results Three main themes were identified to provide an overview on peer-support services for mental health consumers in Asia: the delivery of such services in Asia; Asian consumers' perceptions of them; and factors affecting their implementation. Discussion Given their relative novelty in Asia, findings from this review represent useful insights for organizations and policy administrators when formulating such services. Implications for Practice Future research should also focus on evaluating the effectiveness of such services in Asia and comparing their outcomes with other regions.

Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts / 药学学报

A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the tmax of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the Cmax and AUC0-48 h of chlorogenic acid, the Cmax, AUC0-48 h and AUC0-∞ of pinoresinol di-O-glucopyranoside, and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.

Application status and analysis of Fu's subcutaneous needling in the treatment of peripheral facial paralysis / 中国针灸

This paper summarizes the status of application and research of Fu's subcutaneous needling for peripheral facial paralysis, and the characteristics of different stages of peripheral facial paralysis treated with Fu's subcutaneous needling are analyzed from the aspects of intervention timing, protocol design, needle insertion point, sweeping and reperfusion activity, tube retaining time and acupuncture frequency. It is found that there are no norms and standards in sweeping and reperfusion, tube retention and acupuncture frequency in clinical application，and the exploration of staged treatment is insufficient in the research. In the future, it is necessary to form standardized operation to promote clinical promotion, and improve the research on treatment rules and mechanism according to the characteristics of disease stage.

Adjuvant rice optimization of rice-steamed Rehmanniae Radix and its anti-osteoporosis effect / 中国中药杂志

The present study aimed to investigate the effect of various adjuvant rice on the quality of rice-steamed Rehmanniae Radix(RSRR) with Japonica rice, millet, yellow rice, black rice, and glutinous rice as raw materials, and analyze the anti-osteoporosis effect of RSRR by the optimal adjuvant rice. On the basis of the established UPLC-MS/MS method for the determination of the content of catalpol and rehmannioside D, comprehensive weighted scoring method was employed to evaluate the effect of various auxiliary rice on the quality of RSRR with the content of catalpol and rehmannioside D, character score, and taste score as indicators to optimize adjuvant rice. The osteoporosis model was induced by ovariectomy in rats. SD rats were randomly divided into a sham operation group, a model group, a positive control group, and low-dose and high-dose groups of Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, and Epimedii Folium-RSRR. After treatment for 12 weeks, body weight, bone calcium content, and bone mineral density were mea-sured. The results showed that Japonica rice was selected as the optimal adjuvant due to the highest comprehensive score of RSRR steamed by Japonica rice. Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, as well as Epimedii Folium-RSRR, could improve osteoporosis by increasing bone calcium content and bone mineral density. RSRR was superior to Rehmanniae Radix in improving osteo-porosis. However, there was no significant difference between RSRR and steamed Rehmanniae Radix. This study confirmed that Japo-nica rice was the optimal adjuvant rice of RSRR and verified the anti-osteoporosis effect of RSRR, which laid a foundation for further research on the pharmacological action and mechanism of RSRR.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.