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Abstract Background Acute pain is a major concern after arthroscopic shoulder surgery, supraclavicular brachial plexus blockade has shown favorable postoperative analgesic effects. However, its duration of analgesia does not meet clinical needs. We aimed to explore whether the combination of different local anesthetic adjunct can prolong the analgesic duration of supraclavicular brachial plexus block for arthroscopic shoulder surgery. Methods In this prospective randomized controlled trial, we allocated 80 patients into four groups: Group DMD (dexamethasone 10 mg + ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group DM (ropivacaine 100 mg + dexmedetomidine 50 µg + magnesium sulfate 250 mg), Group M (ropivacaine 100 mg + magnesium sulfate 250 mg) and Group D (ropivacaine 100 mg + dexmedetomidine 50 µg). The primary outcome was the time to first request for analgesia. Secondary outcome measures included cumulative opioid consumption at 6, 12, 18, 24, and 48 h postoperatively, VAS scores at 6, 12, 18, 24, and 48 h postoperatively and so on. Results The time to first request for analgesia in Group DMD was significantly longer than Group DM (P = 0.011) and Group M (P = 0.003). The cumulative opioid consumption at 18 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.002) and Group M (P = 0.007). The cumulative opioid consumption at 24 h postoperatively in Group DMD was significantly lower than in Group DM (P = 0.016). The VAS score at 6 h postoperatively in Group DMD was significantly lower than in Group DM and Group M. The VAS score at 12 h postoperatively in Group DMD was significantly lower than in Group M. For American Shoulder and Elbow Surgeons Score, Group DMD had a better score than Group DM and Group D. Conclusions The analgesic efficacy of supraclavicular brachial plexus blockade combined with dexamethasone, magnesium sulfate, and dexmedetomidine is significantly superior to the combination of magnesium sulfate and dexmedetomidine, and significantly superior to the use of magnesium sulfate alone. Trial registration This trial was registered in Chinese Clinical Trial Registry. (ChiCTR2200061181, Date of registration: June 15, 2022, http://www.chictr.org.cn )

[Introduction] In the face of energy scarcity and carbon reduction imperatives, the transition to clean energy centered on electricity is crucial. To achieve this, power system development must prioritize stability, automation and intelligence. Artificial intelligence (AI) technology is a key means to realize this goal. [Method] This paper introduced the carbon emissions of domestic and foreign power systems at first, and pointed out the difficulties and feasible solutions for low-carbon development of the power system in China on this basis. Then, the application and prospect of AI technology in power system development were discussed. [Result] In response to the transition to low-carbon and low-energy power systems, a series of low-carbon development routes, such as integration of capital and resources in the thermal power industry, low-carbon transition (such as the application of carbon capture technology), and promoting the consumption of and smooth replacement by clean energy, were proposed in this paper. It was also noted that AI technology will play a crucial role in automating, intelligentizing and optimizing power systems, with wide-ranging applications in power dispatching, relay protection, power equipment management, power system stability evaluation, and decision-making processes. [Conclusion] As third-generation AI technology continues to evolve and fourth-generation AI technology emerges, the application of AI technology in the power system will become increasingly widespread.

Background: Postoperative pain is a prevalent concern following a cesarean section. This study aimed to investigate the effect and mechanism of low-dose (0.1 mg/kg) esketamine on postoperative pain management in pregnant women undergoing cesarean sections, specifically in cases where both patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia (PCEA) were employed. Methods: Pregnant women intending to undergo elective cesarean section were divided into four subgroups based on the intravenous administration of esketamine and the specific analgesia methods employed: E1 (0.1 mg/kg esketamine + PCEA), E2 (0.1 mg/kg esketamine + PCIA), C1 (saline + PCEA), and C2 (saline + PCIA). The primary outcome was the maximum pain score within 24 h postoperatively. Secondary outcomes included the pressure pain threshold and tolerance at 30 min and 24 h postoperatively, along with the inflammation and adverse event index scores. Results: A total of 118 pregnant women were assigned to the four groups: E1 (n = 29), E2 (n = 29), C1 (n = 30), and C2 (n = 30). Compared with those in the control groups (C1 + C2), the maximum postoperative pain scores within 24 h in the esketamine groups (E1 + E2) were significantly lower (4 [2–5] vs. 4 [4–6], P = 0.002), and the E1 group exhibited superior analgesic effects compared with other groups. No significant differences were observed in postoperative hyperalgesia or inflammation across the four groups. Notably, esketamine combined with PCIA increased the incidence of postoperative nausea and vomiting (7 [25 %] vs. 0 [0 %]; P = 0.005). Conclusion: The administration of low-dose (0.1 mg/kg) esketamine effectively alleviates pain following cesarean section, and the analgesic effect is notably enhanced in combination with PCEA. Importantly, these effects do not appear to be mediated through anti-inflammatory mechanisms or the inhibition of hyperalgesia. Clinical trial registration number: NCT05414006.

Energy utilization rates have been largely improved thanks to the wide application of smart grids, thereby realizing the reliable, economic and efficient operation of the grids. However, such an application is also accompanied by many security issues. In response to the many problems within existing security schemes, such as not supporting the communication between heterogeneous cryptosystems, low security levels and a low data retrieval efficiency, a heterogeneous signcryption (HSC) scheme that supports a trusted multi-ciphertext equality test (MET) is proposed. The adoption of the HSC helps to identify secure communications from identity-based cryptosystems to certificateless cryptosystem, eliminates the certificate management problems in the traditional public key cryptography scheme, and ensures the confidentiality and authentication of power data. The introduction of the MET technology can avoid the high cost of equality test calculations after grouping ciphertexts in pairs. Using blockchain and smart contract technologies ensure the credibility of test results and eliminates the reliance on trusted cloud servers. Under the random oracle model, on the basis of the bilinear Diffie-Hellman, the computational Diffie-Hellman and the q-strong Diffie-Hellman problems, this paper proves that the scheme proposed herein meets the requirements of indistinguishability and one-way security under adaptive choice ciphertext attacks, and the unforgeability under the adaptive choice message attack. From the findings of the analysis, it has been shown that the proposed scheme satisfies more security attributes and requires lower computational overhead compared to similar schemes.

In conventional message communication systems, the practice of multi-message multi-receiver signcryption communication encounters several challenges, including the vulnerability to Key Generation Center (KGC) attacks, privacy breaches and excessive communication data volume. The KGC necessitates a secure channel to transmit partial private keys, thereby rendering the security of these partial private keys reliant on the integrity of the interaction channel. This dependence introduces concerns regarding the confidentiality of the private keys. Our proposal advocates for the substitution of the KGC in traditional certificateless schemes with blockchain and smart contract technology. Parameters are publicly disclosed on the blockchain, leveraging its tamper-proof property to ensure security. Furthermore, this scheme introduces conventional encryption techniques to achieve user identity privacy in the absence of a secure channel, effectively resolving the issue of user identity disclosure inherent in blockchain-based schemes and enhancing communication privacy. Moreover, users utilize smart contract algorithms to generate a portion of the encrypted private key, thereby minimizing the possibility of third-party attacks. In this paper, the scheme exhibits resilience against various attacks, including KGC leakage attacks, internal privilege attacks, replay attacks, distributed denial of service attacks and Man-in-the-Middle (MITM) attacks. Additionally, it possesses desirable security attributes such as key escrow security and non-repudiation. The proposed scheme has been theoretically and experimentally analyzed under the random oracle model, based on the computational Diffie-Hellman problem and the discrete logarithm problem. It has been proven to possess confidentiality and unforgeability. Compared with similar schemes, our scheme has lower computational cost and shorter ciphertext length. It has obvious advantages in communication and time overhead.

Abstract Hypertrophic scar (HS) is an abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs patients’ quality of life. Numerous studies have shown that pressure garment therapy (PGT) is an effective treatment for preventing hypertrophic scars. Herein, we found that mechanical stress stimulates the neuropilin 1 (NRP1) expression through screening GSE165027, GSE137210, and GSE120194 from Gene Expression Omnibus (GEO) database and bioinformatics analysis. We verified this stimulation in the human hypertrophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression increased LATS1 and pYAP enrichment, thus repressing the expression of YAP. Functionally, the knockdown of NRP1 promoted the expression of LATS1, thus decreasing the expression of YAP and inhibiting endothelial cell proliferation. Furthermore, co-immunoprecipitation analysis confirmed that NRP1 binds to YAP, and mechanical compression disrupted this binding, which resulted in the promotion of YAP relocation to nuclear. In conclusion, our results indicated that NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Mechanical pressure can release YAP bound to NRP1, which explains the phenomenon that mechanical stress increases YAP in the nucleus. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures.

Background: Pain management after lung resection plays a crucial role in reducing postoperative pulmonary complications (PPCs). This study aimed to examine the effect of postoperative esketamine infusion as an adjunct to opioid analgesia on ventilation and pulmonary complications in patients underwent lung resection. Methods: Patients undergoing video-assisted thoracoscopic lung resection were randomly assigned to either the esketamine group or the control group. The esketamine group received a 24-h infusion of 1.5 mcg/ml sufentanil combined with 0.75 mcg/ml esketamine after surgery, while the control group received 1.5 mcg/ml sufentanil alone. The primary outcome measure was low minute ventilation, and the secondary outcome measures were hypoxemia, PaO2/FiO2 levels, postoperative pulmonary complications, hospital stay duration, ambulation time, Visual Analogue Scale (VAS) score, depression and anxiety levels, sleep quality, and analgesia satisfaction. Results: 80 patients were randomly divided into two groups: the esketamine group (n = 40) and the control group (n = 40). The esketamine group exhibited notably reduced incidence of low minute ventilation (P = 0.014), lower occurrence of postoperative pulmonary complications (PPCs) compared to the control group (P = 0.039), and decreased incidence of hypoxemia (P = 0.003). Furthermore, the esketamine group showed improved outcomes with lower VAS scores on the second postoperative day and enhanced sleep quality (P

Introduction: Postoperative nausea and vomiting (PONV) and pain are common and distressing complications in patients undergoing surgery. However, it remains uncertain whether timing of the postoperative course or the diel rhythm influences the occurrence of PONV or severe pain. Therefore, we aimed to explore the temporal distribution of PONV and severe pain. Material and methods: In this prospective observational study, we enrolled patients aged 18–65 years with American Society of Anesthesiologists classifications I–III, who were scheduled for surgery under general anesthesia. Patients were visited postoperatively at regular intervals (every 6 h over a 24-h period). Incidence of PONV was recorded and categorized based on real-time divisions: before dawn (00:00–05:59), morning (06:00–11:59), afternoon (12:00–17:59), and evening (18:00–23:59) and as sequential periods (i.e., 0–6, 6–12, 12–18, and 18–24 h). Severe pain and use of additional remedies were also recorded. Results: A total of 724 patients were included in the final analysis. Of these, 14.92 % experienced PONV within the first 6 h, and 8.29 % received antiemetic therapy. Occurrence of PONV and administration of remedies declined over the 24-h postoperative period. The lowest rate of PONV was observed during the pre-dawn hours (5.66 %). There was no statistically significant difference in the incidence of PONV 24-h postoperatively between surgeries with different end times. Patients underwent orthopedic surgeries had the highest incidence of PONV during 18:00–23:59, gynecological surgery patients had the highest incidence at 12:00–17:59, and 6:00–11:59 for other surgery patients. All patients had the lowest incidence during 0:00–5:59. During the initial 6-h postoperative period, 24.59 % of patients experienced severe pain, which declined in the remaining episodes. Patients who underwent orthopedic and gynecological surgeries exhibited similar temporal patterns and distribution characteristics of PONV and severe pain. Discussion: Both PONV and severe pain declined within the 24-h postoperative period, particularly within the first 6 h. Additionally, the onset patterns of PONV vary among patients undergoing different types of surgeries, all patients demonstrated decreased susceptibility to PONV between 00:00–05:59. Our findings enhance prevention and treatment strategies within an optimized timeframe during the postoperative course.

In view of the problems of inefficient data encryption, non-support of malicious user revocation and data integrity checking in current smart grid data sharing schemes, this paper proposes a blockchain-based multi-authority revocable data sharing scheme in the smart grid. Using online/offline encryption technology with hybrid encryption technology enhances the encryption performance for the data owner. The use of user binary tree technology enables the traceability and revocability of malicious users. The introduction of multiple attribute authorization authorities eliminates the threat of collusive attacks that exist in traditional data-sharing schemes. In addition, the semi-honest problem of third-party servers is solved by uploading data verification credentials to the blockchain. The security analysis results show that the scheme can resist selective plaintext attacks and collusion attacks. The performance analysis results show that the proposed scheme has lower computational overhead and better functionality than similar schemes, which is suitable for secure data sharing in smart grids.

Objective: This study aimed to compare the effectiveness and safety of different titrated methods used to determine individual positive end-expiratory pressure (PEEP) for intraoperative mechanical ventilation in female patients undergoing general anesthesia in different operative positions, and provide reference ranges of optimal PEEP values based on the titration. Methods: A total of 123 female patients who underwent elective open abdominal surgery under general anesthesia were included in this study. After endotracheal intubation, patients' body position was adjusted to the supine position, Trendelenburg positions at 10° and 20° respectively. PEEP was titrated from 20 cmH2O to 4 cmH2O, decreasing by 2 cmH2O every 1 min. Electrical impedance tomography (EIT), hemodynamic and respiratory mechanics parameters were continuously monitored and recorded. Optimal PEEP values and reference ranges were respectively calculated based on optimal EIT parameters, mean arterial pressure (MAP), and lung dynamic compliance (Cdyn). Results: EIT-guided optimal PEEP was found to have higher values than those of the MAP-guided and Cdyn-guided methods for all three body positions (P

Integrated circuit technology has undergone significant advancements and progress over the past few decades. However, as the demand to further shrink circuit sizes increases, traditional IC interconnections face challenges such as RC delay, energy loss, and interconnect interference, which become increasingly prominent. Optical interconnection emerges as a promising solution to mitigate these issues by enabling reductions in circuit size, power consumption, and signal delay. In this article, we propose a novel lateral Si0.15Ge0.85/Ge/Si0.15Ge0.85 p-i-n double-heterojunction laser array, leveraging SiN stress as a key component. Our study focuses on the EL emission properties of individual lasers within the array, the distribution of SiN stress within the device, and the impact of stress on the laser properties. Additionally, we design a Si0.15Ge0.85/SiO2 distributed Bragg reflector (DBR) tailored for the laser array. Simulation results demonstrate a peak luminescence wavelength of 1849 nm and a threshold current density of 190 kA/cm2 at 300 K.

Keloids are common benign cutaneous pathological fibrous proliferation diseases, which are difficult to cure and easily recur. Studies have shown that fibroblast growth factor receptor-1 (FGFR1) was enhanced in pathological fibrous proliferation diseases, such as cirrhosis and idiopathic pulmonary fibrosis (IPF), suggesting the FGFR1 pathway has potential for keloid treatment. Derazantinib is a selective FGFR inhibitor with antiproliferative activity in in vitro and in vivo models. The present study determined the effects of derazantinib on human keloid fibroblasts (KFs). Cell viability assay, migration assay, invasion assay, immunofluorescence staining, quantitative polymerase chain reaction, Western blot analysis, HE staining, Masson staining, and immunohistochemical analysis were used to analyze the KFs and keloid xenografts. In this study, we found that derazantinib inhibited the proliferation, migration, invasion, and collagen production of KFs in vitro. The transcription and expression of plasminogen activator inhibitor-1 (PAI-1), which is closely related to collagen deposition and tissue fibrosis, was significantly inhibited. Also, derazantinib inhibited the expression of FGFR1 and PAI-1 and reduced the weight of the implanted keloid from the xenograft mice model. These findings suggest that derazantinib may be a potent therapy for keloids via FGFR signaling.

Abstract Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80.

IntroductionAccurate and accessible predictors of chronic postsurgical pain (CPSP) to identify high-risk postsurgical patients are prerequisite for preventive and interventional strategies. We investigated the incidence and risk factors of CPSP after abdominal surgery, with a focus on plasma immunological markers.Materials and methodsThis was a retrospective analysis of patients who underwent abdominal surgery under general anesthesia at a tertiary center between January 2021 and January 2022. The preoperative demographics, laboratory test data, and surgical factors of the participants were collected from the electronic medical record system. Postoperative pain intensity and living conditions at 1 year after discharge from the hospital were assessed via a phone survey. Univariate and multivariate analyses were used to explore independent risk factors associated with CPSP.ResultsA total of 968 patients were included, and 13.53% (n = 131 of 968) of patients reported CPSP 1 year after surgery. Patients with older age, open surgery, higher American Association of Anesthesiologists classification, patient-controlled intravenous analgesia application, longer surgery duration, higher postoperative absolute neutrophil count, and neutrophil-lymphocyte ratio (NLR), lower postoperative absolute lymphocyte count, and higher white blood cell count, were more likely to suffer from CPSP. A changed ratio of NLR (postoperative to preoperative) ≥ 5 significantly correlated with CPSP, moderate to severe pain, maximum numeric rating score since discharge from the hospital, and affected quality of life.DiscussionThe changed ratio of NLR could be used for the early identification of patients at risk for CPSP and affect the quality of life to alert the clinician to undertake further assessment.

Background. Autoimmune pancreatitis (AIP) usually responds dramatically to steroid therapy. Occasionally, however, misdiagnosed patients have undergone pancreaticoduodenectomy. This study is aimed at providing useful information to improve the accuracy of diagnosis before surgery and thus avoid unnecessary resections in patients with AIP. Methods. From January 2015 to February 2020, a series of patients were enrolled, having undergone pancreaticoduodenectomy for presumed malignancy. AIP diagnoses were confirmed by postoperative pathology. The demographic and clinical data of the AIP patients were evaluated. The main diagnostic criteria (HISORt, Asian, and ICDC) for AIP were applied to assess whether and how unnecessary surgery could have been avoided. Results. A total of 124 cases of pancreaticoduodenectomy were performed for presumed malignancy. Six patients were diagnosed with benign disease and five with AIP. The prevalences of benign disease and AIP were 4.8% and 4%, respectively. Four patients were female and 1 male, with a mean age of 60.0 years old. Jaundice, pain, and weight loss were observed in 100%, 20%, and 40% of AIP patients, respectively. The radiologic features of the AIP patients were a diffusely enlarged gland (40.0%), a focally enlarged gland (40.0%), pancreatic ductal dilatation (60.0%), upstream parenchymal atrophy (20.0%), bile duct thickening (66.0%), and bile duct stricture (40.0%). Based on the diagnostic criteria for AIP, surgery could have been avoided in two cases. Conclusions. IgG4 measurement and integrated use of major diagnostic criteria should be emphasized in every patient eligible for pancreaticoduodenectomies.

BackgroundSurgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported.MethodsThis open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS).DiscussionThis trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT.Clinical trial registrationhttps://clinicaltrials.gov/, identifier (NCT05225116).

ObjectiveThe diurnal rhythm profile of human basal pain sensitivity and its association with sympathetic nerve activity are not fully understood. This study aimed to examine rhythmic changes in experimental pain sensitivity and skin sympathetic nerve activity in healthy volunteers.MethodsThirty healthy volunteers were included in the study. Experimental pain sensitivity, including pressure pain threshold and tolerance, cold pain threshold (CPT) and tolerance, skin sympathetic nerve activity, and cardiovascular parameters (including heart rate, cardiac output, and peripheral vascular resistance) at six time points throughout the day (08:00, 12:00, 16:00, 20:00, 00:00, and 04:00) were sequentially measured. Circadian rhythm analysis was performed on the mean values of the different measurements and individual subjects.ResultsSignificant differences were found in experimental pain sensitivity, skin sympathetic nerve activity, and non-invasive cardiovascular parameters at different time points (P < 0.05). The minimum measured values of all four types of experimental pain sensitivity were consistently observed at 04:00. Rhythmical analysis showed that the mean values of pressure pain threshold (meta2d P = 0.016) and skin sympathetic nerve activity (meta2d P = 0.039) were significant. Significant diurnal rhythms in pain sensitivity and skin sympathetic nerve activity existed in some individuals but not in others. No significant correlation between experimental pain sensitivity and skin sympathetic nerve activity was found at any time point (P > 0.05).ConclusionSignificant diurnal fluctuations were observed in different pain sensitivities and skin sympathetic nerve activity. No significant correlation between experimental pain sensitivity and sympathetic excitability at different times was found; the reasons for these phenomena remain to be further studied.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039709].

Abstract Background Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Although some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. In various diseases, dysregulation of lncRNA is common, but its role has not been fully elucidated. In recent years, the birth of the “competitive endogenous RNA” theory has promoted our understanding of lncRNAs. Methods To identify the key lncRNAs in melanoma, we reconstructed a global triple network based on the “competitive endogenous RNA” theory. Gene Ontology and KEGG pathway analysis were performed using DAVID (Database for Annotation, Visualization, and Integration Discovery). Our findings were validated through qRT-PCR assays. Moreover, to determine whether the identified hub gene signature is capable of predicting the survival of cutaneous melanoma patients, a multivariate Cox regression model was performed. Results According to the “competitive endogenous RNA” theory, 898 differentially expressed mRNAs, 53 differentially expressed lncRNAs and 16 differentially expressed miRNAs were selected to reconstruct the competitive endogenous RNA network. MALAT1, LINC00943, and LINC00261 were selected as hub genes and are responsible for the tumorigenesis and prognosis of cutaneous melanoma. Conclusions MALAT1, LINC00943, and LINC00261 may be closely related to tumorigenesis in cutaneous melanoma. In addition, MALAT1 and LINC00943 may be independent risk factors for the prognosis of patients with this condition and might become predictive molecules for the long-term treatment of melanoma and potential therapeutic targets.

Abstract Background The biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats. Methods Wound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs’ number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203. Results We found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs’ numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA. Conclusion Our findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing.

Background: Scald burns in the neonate are rare in literature, especially major full-thickness injuries in newborns. However, burns are the third most common cause of accidental death among children in the United States. We hope that this report can provide us a new insight for guiding the timing of surgical treatment and the choice of the surgical scheme in severe burn neonates. Case presentation: In this case report, we demonstrate a case of a three-hour-old neonate, who suffered from severe scald burn injuries of 14% of the total body surface area (TBSA). Nearly two weeks after conservative treatment, the wounds showed no sign of healing. Escharotomy following skin grafting was done after the stabilization of the neonate. The neonate was discharged 32 days after injury. Conclusions: Through the review of this case report, we suggest we should pay attention to the following points. First, we should always pay attention to the blood supply of the extremities of the patient, and appropriately relax the indications for deep fasciotomy to reduce the disability rate. Secondly, we should pay special attention to the respiratory system of the newborn, especially for those after cesarean delivery. Moreover, the early application of broad-spectrum antibiotics should be conducted. Third, we should choose antibiotics with less hepatorenal toxicity, and adjust the dosage according to the body surface area of the neonate. Finally, skin grafting is an appropriate treatment and should be done as soon as possible. Keywords: Scald burns, Neonate

Abstract Background Autologous epidermal basal cell suspension therapy has been proven to be one of the most effective treatments for full-thickness wounds. However, we found there remain obvious defects that significantly confined the utilization and function of the epidermal basal cells (EBCs), especially the epidermal stem cells (ESCs) in it. This study investigated whether precoating fibronectin (FN) on the wound bed before spraying EBCs could overcome these defects and further explored its possible mechanisms. Methods In the in vitro study, EBCs were isolated from the donor skin of patients who needed skin grafting. Different concentrations of FN were used to precoat culture dishes before cell culture; the adherent efficiency, proliferation and migration ability of ESCs were analyzed and compared with traditional collagen IV precoating. In the in vivo study, Sprague–Dawley (SD) rats with full-thickness skin wounds were selected as full-thickness wounds’ model. For the experiment groups, 20 μg/ml FN was precoated on the wound bed 10 min before EBC spray. The quality of wound healing was estimated by the residual wound area rate, wound healing time, and hematoxylin and eosin (H&E) staining. Expression of ESC markers, neovascular markers, inflammation markers, and collagen formation and degradation markers was elucidated by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and RT-qPCR analysis. Results The in vitro study showed that the dishes precoated with 20 μg/ml FN had a similar adherent efficiency and colony formation rate with collagen IV, but it could improve the proliferation and migration of ESCs significantly. Similarly, in the in vivo study, precoating FN on wound bed before EBC spray also significantly promote wound healing by improving ESCs’ utilization efficiency, promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. Conclusion FN precoating wound bed before EBC spray could significantly promote full-thickness wound healing by improving the utilization and function of the ESCs and further by promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. Graphical abstract

Deep brain stimulation (DBS) is a neurosurgical technique that regulates neuron activity by using internal pulse generators to electrodes in specific target areas of the brain. As a blind treatment, DBS is widely used in the field of mental and neurological diseases, although its mechanism of action is still unclear. In the past 10 years, DBS has shown a certain positive effect in animal models and patients with Alzheimer's disease (AD), but there are also different results that may be related to the stimulation parameters of DBS. Based on this, determining the optimal stimulation parameters for DBS in AD and understanding its mechanism of action are essential to promote the clinical application of DBS in AD. This review aims to explore the therapeutic effect of DBS in AD, and to analyze its stimulation parameters and potential mechanism of action. The keywords “Deep brain stimulation” and “Alzheimer's Disease” were used for systematic searches in the literature databases of Web of Science and PubMed (from 1900 to September 29, 2020). All human clinical studies and animal studies were reported in English, including individual case studies and long-term follow-up studies, were included. These studies described the therapeutic effects of DBS in AD. The results included 16 human clinical studies and 14 animal studies, of which 28 studies clearly demonstrated the positive effect of DBS in AD. We analyzed the current stimulation parameters of DBS in AD from stimulation target, stimulation frequency, stimulation start time, stimulation duration, unilateral/bilateral treatment and current intensity, etc., and we also discussed its potential mechanism of action from multiple aspects, including regulating related neural networks, promoting nerve oscillation, reducing β-amyloid and tau levels, reducing neuroinflammation, regulating the cholinergic system, inducing the synthesis of nerve growth factor.

Vibrio (V.) vulnificus infection is a rare disease whose death rates exceed 50% despite aggressive antibiotic treatment and surgical debridement. The aim of this study was to assess the ability of specific anti-V. vulnificus immunoglobulins Y (IgYs) for preventing and treating V. vulnificus infections. IgYs were produced by immunizing egg laying hens with inactivated whole cell bacteria. Peritoneal cytokines, blood’s bacterial load, and survival curves were obtained from both prophylactic and therapeutic mouse models. The results showed that the specific IgYs (i) inhibited the growth of V. vulnificus in vitro, (ii) dramatically reduced the inflammatory response and blood’s bacterial load, and (iii) improved the survival rate of V. vulnificus-infected mice. These results prove that anti-V. vulnificus IgYs can be markedly effective means for the prophylaxis and the therapy of V. vulnificus infections.

The aim of this study was to find out neuron (-like) cells in peripheral organs by cell markers in rats. Adult male Sprague-Dawley rats were anaesthetized. Their organs including brain, heart, lung, liver, kidney, stomach, duodenum, and ileum were harvested. The mRNA and protein in these organs were extracted. RNA sequencing (RNA-Seq) was carried out, and NeuN, a “specific” marker for neuronal soma, was assayed with Western blotting. The sections of the aforementioned organs were obtained after a routine fixation (4% methanal)-dehydration (ethanol)-embedding (paraffin) process. NeuN in the sections and seven non-neuronal cell lines was analyzed by immunofluorescence (IF) or immunohistochemistry (IHC). Neuronal markers, such as Eno2, NeuN (Rbfox3), choline acetyltransferase (Chat), as well as tyrosine hydroxylase (Th), and neuronal-glial markers, e.g., glial fibrillary acidic protein (Gfap), S100b, 2′, 3′-cyclic nucleotide 3′-phosphodiesterase (Cnp), and other related markers, were positively expressed in all the organs at mRNA level. NeuN was further analyzed by Western blotting. The IF and IHC assays showed that NeuN-positive cells were distributed in all the peripheral tissues (mainly peri-nuclear NeuN-positive cells) though with different patterns from that in brain (nuclear NeuN-positive cells), and a NeuN-negative tissue could not be found. Especially, NeuN and Myl3 co-expressed in the cytoplasm of myocardial cells, suggesting that NeuN could possess other functions than neuronal differentiation. Also, the protein was positively expressed in seven non-neuronal cell lines. Our findings suggested that NeuN-positive cells exist widely, and without identification of its distribution pattern, the specificity of NeuN for neurons could be limited.

Background/Aims: Little is known how miR-203 is involved in epidermal stem cells (ESCs) differentiation and scar formation. Methods: We first used luciferase assay to determine the interaction of miR-203 with the 3’-UTR in regulation of Hes1 expression. We then used flow cytometry to analyze the effects of miR-203 expression on the differentiation of ESCs to MFB by determination of CK15 ratio and α-SMA. To confirm the results of flow cytometry analysis, we used Western blot to examine the expression of α-SMA, Collagen I (Col I), and Collagen III (Col III), as well as the expression of Notch1, Jagged1, and Hes1 in ESCs after the treatment of pre-miR-203 or anti-miR-203. Finally, we examined the effects local anti-miR-203 treatment on would closure and scar formation using a mouse skin wound model. Results: Pre-miR-203 treatment increased ESCs differentiation to MFB cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. Local treatment of anti-miR-203 could accelerate wound closure and reduce scar formation in vivo, which was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment. Finally, we confirmed that anti-miR-203 treatment could inhibit ESCs differentiation in vivo via increasing Hesl expression. Conclusion: Taken together, our results suggested that overexpression of miR-203 in ESCs after skin wound may be a critical mechanism underlying the scar formation.

Abstract Background Basic fibroblast growth factor (bFGF) plays an important role in promoting wound healing and reducing scar, but the possible molecular mechanisms are still unclear. Our previous studies have found that activating the Notch1/Jagged1 pathway can inhibit the differentiation of epidermal stem cells (ESCs) to myofibroblasts (MFB). Herein, we document that bFGF reduces scar by inhibiting the differentiation of ESCs to MFB via activating the Notch1/Jagged1 pathway. Methods In in-vitro study, ESCs were isolated from 10 neonatal SD rats (1–3 days old), cultured in keratinocyte serum-free medium, and divided into six groups: bFGF group, bFGF + SU5402 group, bFGF + DAPT group, siJagged1 group, bFGF + siJagged1 group, and control group. Jagged1 of the ESCs in the siJagged1 group and bFGF + siJagged1 group was knocked down by small-interfering RNA transfection. Expression of ESC markers (CK15/CK10), MFB markers (α-SMA, Collagen I, Collagen III), and Notch1/Jagged1 components (Jagged1, Notch1, Hes1) was detected by FCM, qRT-PCR, and western blot analysis to study the relationships of bFGF, ESCs, and Notch1/Jagged1 pathway. In in-vivo study, the wound healing time and scar hyperplasia were observed on rabbit ear scar models. The quality of wound healing was estimated by hematoxylin and eosin staining and Masson staining. Expression of ESC markers, MFB markers and Notch1/Jagged1 components was elucidated by immunohistochemistry, immunofluorescence, and western blot analysis. Results The in-vitro study showed that bFGF could significantly upregulate the expression of ESC markers and Notch1/Jagged1 components, while downregulating the expression of MFB markers at the same time. However, these effects could be obviously decreased when we knocked down Jagged1 or added DAPT. Similarly, in in-vivo study, bFGF also exhibited its functions in inhibiting the differentiation of rabbit ESCs to MFB by activating the Notch1/Jagged1 pathway, which improved the wound healing quality and alleviated scar significantly. Conclusion These results provide evidence that bFGF can reduce scar by inhibiting the differentiation of ESCs to MFB via the Notch1/Jagged1 pathway, and present a new promising potential direction for the treatment of scar.

The purpose of this systematic review and meta-analysis is to assess the clinical effectiveness and safety of the medical hydrogel dressings used in skin wounds and therefore to weight the evidence for their clinical application. PubMed/Medline (1980–2019), Cochrane Library (1980–2019), ClinicalTrials.gov, Cochrane CENTRAL, Chinese Journal Full-text Database (CNKI, 1994–2019), and China Biomedy Medicine disc (CBM, 1978–2019), Chinese Scientific Journal Database (VIP, 1989–2019), and Wanfang Database (WFDATA, 1980–2019) were searched to identify relevant clinical trials and studies. Forty-three studies that assessed hydrogel vs. non-hydrogel dressings were identified. Compared to the latter, hydrogel dressings associated with a significantly shortened healing time of degree II burn (superficial and deep) wounds, diabetic foot ulcers, traumatic skin injuries, radioactive skin injuries, dog bites, and body surface ulcers. In addition, hydrogel dressing obviously increased the cure rate of diabetic foot ulcers, surgical wounds, dog bites, and body surface ulcers. Moreover, hydrogel dressing significantly relieved pain in degree II burn (superficial and deep) wounds, traumatic skin injuries, and laser treatment-induced wounds. However, no significant differences obtained between hydrogel and non-hydrogel dressings in the healing time of surgical wounds, the cure rate of inpatients' pressure ulcers, and phlebitis ulcers. This comprehensive systematic review and meta-analysis of the available evidence reveals that the application of hydrogel dressings advances the healing of various wound types and effectively alleviates the pain with no severe adverse reactions. These results strongly indicate that hydrogel products are effective and safe in wound management.

Chinese cinnamon (Cinnamomum cassia) has economic value as an aromatic and medicinal plant, and its bark oil has a very high trans-cinnamaldehyde content. To gain insight into the accumulation of bark oil and the biological mechanisms which permit the accumulation of a high level of aldehydes in C. cassia bark, the morphology and histochemistry of oil cells and the specialization in its walls were assessed by light and fluorescence microscopy. The histochemical tests localized in situ the main chemical classes of metabolites in oil cells, which included aldehydes, lipids and terpenoids. In oil cells the aldehydes distributed in the area surrounding the oil sac were compartmentalized from lipid compounds in the center; the oil sac in an oil cell was attached by multiple cupules rather than one cupule. The autofluorescence of oil-cell walls was attributed to the presence of suberin and lignin, and was confirmed by different methods. The lignified and suberized walls probably serve as protective barriers against the cytotoxicity of high contents of trans-cinnamaldehyde to the surrounding active cells. These results contribute to our knowledge of the structure of oil cells and accumulation of essential oil in Chinese cinnamon bark.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) can accelerate wound healing by promoting angiogenesis. The biological effects of GM-CSF in angiogenesis and the corresponding underlying molecular mechanisms, including in the early stages of primitive endothelial tubule formation and the later stages of new vessel maturation, have only been partially clarified. This study aimed to investigate the effects of GM-CSF on angiogenesis and its regulatory mechanisms. Employing a self-controlled model (Sprague-Dawley rats with deep partial-thickness burn wounds), we determined that GM-CSF can increase VEGF expression and decrease the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 in the early stages of the wound healing process, which promotes the degradation of the basement membrane and the proliferation of endothelial cells. At later stages of wound healing, GM-CSF can increase the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 and maintain a high VEGF expression level. Consequently, pericyte coverages were higher, and the basement membrane became more integrated in new blood vessels, which enhanced the barrier function of blood vessels. In summary, we report here that increased angiogenesis is associated with GM-CSF treatment, and we indicate that VEGF and the Ang/Tie system may act as angiogenic mediators of the healing effect of GM-CSF on burn wounds.

Background: Most patients are in a noisy environment during abdominal surgery under general anesthesia. This study included patients who underwent abdominal surgery under general anesthesia and established an animal model to determine whether intraoperative noise affects postoperative pain. Materials and methods: This prospective study included 200 patients who underwent abdominal surgery under general anesthesia. Intraoperative noise and electroencephalograms were continuously recorded, and the mean level and time proportion of noise intensity of greater than 70 dB were calculated. Maximum postoperative pain was assessed using a numerical rating scale at 0-12 h and 12-24 h after surgery, and postoperative analgesia consumption in patients receiving patient-controlled intravenous analgesia was recorded. Postoperative pain intensity and electroencephalogram amplitude were compared between patients with high-noise exposure (time proportion of noise intensity greater than 70 dB ≥40%) and low-noise exposure (<40%). Mechanical pain sensitivity was tested in two groups of mice with plantar incisions exposed to 40 dB or 70-100 dB. Results: The time proportion of noise intensity greater than 70 dB was identified as an independent risk factor for postoperative pain intensity (P< 0.001). Pain numerical rating scale 0-12 h (4.5 ± 1.5 vs. 3.7 ± 1.3, P =0.001) and 12-24 h (3.9 ± 1.5 vs. 3.2 ± 1.1, P=0.004) after surgery in patients with high-noise exposure was significantly higher than in patients with low-noise exposure. The electroencephalogram amplitude of patients with high-noise exposure was significantly lower than that of patients with low-noise exposure (P< 0.05). In the mouse model, mechanical hyperalgesia in the 70-100 dB group was significantly greater than that in the 40 dB group (P <0.001). Conclusion: High-level intraoperative noise exposure aggravates the degree of postoperative pain and analgesic needs of patients undergoing abdominal surgery, which may be related to the impact of noise on the neurophysiological activity of the brain and postoperative hyperalgesia. [ABSTRACT FROM AUTHOR]