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Abstract Background As a popularly used analgesic adjuvant, intravenous (IV) lidocaine could reduce the consumption of propofol in painless gastrointestinal (GI) endoscopy. However, whether IV lidocaine could affect the incidence of oxygen-desaturation episodes (ODE) during painless GI endoscopy is still unknown. Therefore, we tested the hypothesis that IV lidocaine could decrease the incidence of propofol-induced ODE and involuntary movements in patients during GI endoscopy. Methods Three hundred twenty-two patients scheduled for GI endoscopy were randomly divided into lidocaine group and control group. After midazolam and sufentanil injection, a bolus of 1.5 mg/kg lidocaine was given and followed by continuous infusion of 4 mg/kg/h in lidocaine group, whereas the same volumes of saline solution in control group. Then, propofol was titrated to produce unconsciousness. The primary outcome was the incidence of ODE during the procedure. The secondary outcomes were the incidence of different degree of hypoxia and corresponding treatments and the involuntary body movements. Results A total of 300 patients were finally included in the analysis, 147 patients in lidocaine group and 153 in control group. The incidence of ODE was 22% in lidocaine group and 39% in control group (OR:0.052; 95%CI: 0.284–0.889; P = 0.018). IV lidocaine also improved the occurrence of different degree of hypoxia (P = 0.017) and needed few treatments (P = 0.028). The incidence of involuntary body movements (14% vs 26%, P = 0.013) and adverse circulatory events was decreased by IV lidocaine. Conclusions IV lidocaine adjuvant to propofol-based sedation could reduce the incidence of oxygen-desaturation episodes and involuntary body movements, with fewer adverse circulatory events. Trial registration Chinese Clinical Trial Registry ChiCTR2100053818. Registered on 30 November 2021.

Objective At present, due to the lack of early observation methods, the effect of the ‘accordion’ technique on the treatment of nonunion of the docking site varies greatly. In this study, color Doppler ultrasound was used to observe the docking site's local changes and investigate the relationship between local microenvironment changes and bone healing after the accordion technique. Methods 30 patients with tibial bone transport treated at the Department of Orthopedics, Second Hospital of Shanxi Medical University, from May 2018 to June 2022, were analyzed retrospectively. Paired‐sample t‐tests were used for data that conformed to a normal distribution, and paired rank‐sum tests were used for before‐and‐after comparisons that did not conform to a normal distribution. There were 26 males and 4 females, aged 47.3 ± 11.7 years. Before bone transport, the defect gap between tibial bone ends was 6.80 ± 3.61 cm. The steps of the accordion technique were as follows: compression for 7 days, ultrasonic study of the microenvironment at the docking site, distraction for 12 days, latency for 7 days, compression for 14 days, then static fixation and radiological study until complete bone healing. Ultrasound was used to detect the size of the hematoma after 7 days of pressure, and the changes in blood flow before and after the ‘accordion' operation. Results All patients were followed up for 11.9 ± 1.9 months. At the last follow‐up, 22 patients achieved bone healing at the docking site after the treatment of the ‘accordion’ technique. There was a linear negative correlation between the size of the hematoma and the time of bone healing at the docking site (r = −0.639, p

Abstract Background Circulatory and respiratory depression are common problems that occur in propofol alone sedation during gastroscopy. As a widely used analgesic adjuvant, intravenous lidocaine can reduce the consumption of propofol during Endoscopic retrograde cholangiopancreatography (ERCP) or colonoscopy. However, it is still unknown the median effective dose (ED50) of propofol when combined with lidocaine intravenously. This study aimed to compare the ED50 of propofol with or without intravenous lidocaine for inserting gastrointestinal endoscope successfully. Methods Fifty nine patients undergoing gastroscopy or gastrointestinal (GI) endoscopy were randomly divided into control group (Group C, normal saline + propofol) or lidocaine group (Group L, lidocaine + propofol). Patients were initially injected a bolus of 1.5 mg/kg lidocaine in Group L, whereas equivalent volume of 0.9% saline in Group C. Anaesthesia was then induced with a single bolus of propofol in all subjects. The induction dose of propofol was determined by the modified Dixon’s up-and-down method, and the initial dose was 1.5 mg/kg in both groups. The primary outcome was the ED50 of propofol induction dose with or without intravenous lidocaine. The secondary outcomes were the induction time, the first propofol bolus time (FPBT: from MOAA/S score ≤ 1 to first rescue bolus propofol), and adverse events (AEs: hypoxemia, bradycardia, hypotension, and body movements). Results Totally, 59 patients were enrolled and completed this study. The ED50 of propofol combined with lidocaine was 1.68 ± 0.11 mg/kg, significantly reduced compared with the normal saline group, 1.88 ± 0.13 mg/kg (P = 0.002). There was no statistical difference in induction time (P = 0.115) and the FPBT (P = 0.655) between the two groups. There was no significantly difference about the AEs between the two groups. Conclusion The ED50 of propofol combined with intravenous lidocaine for successful endoscope insertion in adult patients, was 1.68 ± 0.11 mg/kg significantly reduced compared with the control group. Trial registration Chinese Clinical Trial Registry, No: ChiCTR2200059450. Registered on 29 April 2022. Prospective registration. http://www.chictr.org.cn .

Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1β activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS.

Abstract Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation’s pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

Abstract Background Oxygen-desaturation episodes, blood pressure drops, and involuntary body movement are common problems that occur in propofol-based sedation in the procedure of painless gastrointestinal (GI) endoscopy. As a widely used analgesic adjuvant, intravenous lidocaine can reduce the consumption of propofol during ERCP or colonoscopy. However, it is still unknown how lidocaine affects the incidence of oxygen-desaturation episodes and cardiovascular events, and involuntary movement during painless GI endoscopy. Therefore, we aimed to assess the effectiveness and safety of intravenous lidocaine in propofol-based sedation for GI endoscopy. Methods We will conduct a single-center, prospective, randomized, double-blind, saline-controlled trial. A total number of 300 patients undergoing painless GI procedures will be enrolled and randomly divided into the lidocaine group (Group L) and the control group (Group C). After midazolam and sufentanil intravenous injection, a bolus of 1.5 mg/kg lidocaine was immediately injected and followed by a continuous infusion of 4 mg/kg/h in the lidocaine group, whereas the same volumes of saline solution in the control group. Then, propofol was titrated to produce unconsciousness during the procedure. The primary outcome will be the incidence of oxygen-desaturation episodes. Secondary outcomes will be the incidence of involuntary body movement, discomfort symptoms, propofol consumption, endoscopist, and patient satisfaction. Discussion Propofol-based deep sedation without intubation is widely used in painless GI endoscopy. However, adverse events such as hypoxemia often occur clinically. We expect to assess the effect of lidocaine on reducing the incidence of oxygen-desaturation episodes, cardiovascular events, and involuntary body movement. We believe that the results of this trial will provide an effective and safe method for painless GI endoscopy. Trial registration Chinese Clinical Trial Registry ChiCTR2100053818. Registered on 30 November 2021.

Dipeptidyl peptidase 4 (DPP4) is a serine protease widely distributed in membrane-bound and soluble forms in various tissues and organs throughout the body. DPP4 plays a role in inflammation, immune regulation, cell growth, migration and differentiation. The role of DPP4 in tumors has garnered increasing attention. Previous research has demonstrated that DPP4 contributes to the promotion of cancer in most cancers, and it may play a specific biological function through the variation in tumor cell types and expression forms. However, the expression of DDP4 in different tumor types and its specific mechanism remains unclear. In this review, we describe the structure of DPP4, summarize the recent research progress of its expression and potential mechanisms in common tumors, and discuss the development prospects of DPP4 inhibitors in tumor therapy. Although current research emphasizes the potential of DPP4 as a drug target, the incomplete understanding of its regulatory mechanisms impedes the discovery and development of new therapies against it. Further research on DPP4-related tumors is anticipated to promote its clinical application as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons, progressive loss of visual field, and optic nerve atrophy. Autophagy plays a pivotal role in the pathophysiology of glaucoma and is closely related to its pathogenesis. Targeting autophagy and blocking the apoptosis of RGCs provides emerging guidance for the treatment of glaucoma. Here, we provide a systematic review of the mechanisms and targets of interventions related to autophagy in glaucoma and discuss the outlook of emerging ideas, techniques, and multidisciplinary combinations to provide a new basis for further research and the prevention of glaucomatous visual impairment.

Ingenane-type diterpenoids (ITDs) are distinct components of plants belonging to the genus Euphorbia. These compounds have significant cytotoxic effects on non-small cell lung cancer (NSCLC) cells. However, the underlying molecular mechanism has yet to be reported. To explore the mechanism of the anticancer effect of ITDs, we carried out a network pharmacology prediction study. PPI network suggested that SRC and PI3K had high levels of interaction. In addition, KEGG analysis revealed that these common targets were significantly enriched in the PI3K/Akt signalling pathway. 13-oxyingenol-dodecanoate (13OD) was used for validation after the biological evaluation of some ITDs against NSCLC cells. It demonstrated that 13OD could significantly inhibit the growth of NSCLC cells by inducing apoptosis. The results from molecular docking and Western blotting showed that 13OD interacted with SRC and PI3K and down-regulated the SRC/PI3K/Akt signalling pathway in NSCLC cells. This study provided the underlying mechanism of ITDs against NSCLC. [ABSTRACT FROM AUTHOR]

Objective: At present, due to the lack of early observation methods, the effect of the 'accordion' technique on the treatment of nonunion of the docking site varies greatly. In this study, color Doppler ultrasound was used to observe the docking site's local changes and investigate the relationship between local microenvironment changes and bone healing after the accordion technique. Methods: 30 patients with tibial bone transport treated at the Department of Orthopedics, Second Hospital of Shanxi Medical University, from May 2018 to June 2022, were analyzed retrospectively. Paired‐sample t‐tests were used for data that conformed to a normal distribution, and paired rank‐sum tests were used for before‐and‐after comparisons that did not conform to a normal distribution. There were 26 males and 4 females, aged 47.3 ± 11.7 years. Before bone transport, the defect gap between tibial bone ends was 6.80 ± 3.61 cm. The steps of the accordion technique were as follows: compression for 7 days, ultrasonic study of the microenvironment at the docking site, distraction for 12 days, latency for 7 days, compression for 14 days, then static fixation and radiological study until complete bone healing. Ultrasound was used to detect the size of the hematoma after 7 days of pressure, and the changes in blood flow before and after the 'accordion' operation. Results: All patients were followed up for 11.9 ± 1.9 months. At the last follow‐up, 22 patients achieved bone healing at the docking site after the treatment of the 'accordion' technique. There was a linear negative correlation between the size of the hematoma and the time of bone healing at the docking site (r = −0.639, p < 0.01). According to the Paley healing criteria, 18 of the 22 patients were excellent, and 4 patients were good. Conclusion: Hematoma is necessary for the 'accordion' technique's success in the treatment of nonunion. The size of the hematoma is negatively related to the time of bone healing. The 'accordion' technique can increase the blood flow of tissue around the docking site. Ultrasound can be used to monitor the changes in the microenvironment at the docking site during the 'accordion' technique and guide the exact plan and prognosis of the 'accordion' technique. [ABSTRACT FROM AUTHOR]

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Fruit and vegetable sorting is an indispensable part of postharvest fruit and vegetable production, and the automatic production line with programmable logic control technology as the core provides a new way for the intelligent development of modern agriculture. In the present study, the technologies of data acquisition, data processing, wireless communication, intelligent control and so on were deeply integrated, and a remote-controlled intelligent sorting mechanism for fruit and vegetable was studied, in order to improve the efficiency of fruit and vegetable sorting and reduce the labor cost of local sorting. The remote control sorting schemes were investigated via programmable logic controller (PLC) automatic data acquisition and mechanical control method and distributed network control method based on .NET core architecture, aiming to realize high-speed remote on-line intelligent sorting of fruit and vegetable coordinating appropriate sugar content-quality model. The control strategy and sorting accuracy were simulated based on testing the software and hardware scheme of the sorting technology. Results showed that, compared with the traditional fruit and vegetable sorting technology, this system had advantages in system cost, reaction speed, sorting accuracy, management efficiency, etc. and the fruit and vegetable sorting accuracy could reach to more than 93%, which could realize remote fault diagnosis, save labor cost, and presented the values of generalization and application. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/β-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/β-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP. [Display omitted] [ABSTRACT FROM AUTHOR]

Camellia oleifera flower (COF) is rich in flavonoids and polyphenols, strongly preventing postprandial hyperglycemia and improving diabetes. However, research on the effective ingredients in COF extracts that have hypoglycemic effects is limited, and the mechanism by which COF extracts improve liver insulin resistance and glucose and lipid metabolism still needs to be clarified, requiring further investigation. To systematically clarify the role of COF extracts in improving insulin resistance in diabetes mice and to explore their key targets and mechanisms in anti-type 2 diabetes (T2DM). Ultrafiltration combined with liquid chromatography-mass spectrometry (UPLC-Q-MS) was used to analyze α-glucosidase inhibitors in COF extracts qualitatively. Blood glucose, lipid, oxidative stress, and liver function indicators were detected in the db/db type 2 diabetes mouse model. Then, RNA-seq was used to identify differentially expressed mRNAs (DEGs) in the liver, screen for key genes and metabolic pathways, and validate the results' accuracy through qPCR experiments. 17 α-glucosidase inhibitors were identified as flavonoids from COF. Through db/db type 2 diabetes mouse model, it was indicated that COF could significantly improve symptoms of hyperglycemia and hyperlipidemia, alleviate oxidative stress, and protect liver and pancreatic tissues by regulating key differential genes expressed, including Nek2, Cdk1, Ccnb1, and Ccnb2 via the p53 signaling pathway and ameliorate the insulin resistance effect. This study demonstrated the anti-diabetic effect of COF, explored its potential hypoglycemic target, and provided data support for future T2DM prevention and drug treatment. [Display omitted] • Screening specific α - glucosidase inhibitors from Camellia oleifera flower (COF) extracts. • COF is a natural drug that can improve the symptoms of type 2 diabetes mice. • COF can regulate the expression of key differentially expressed genes such as Nek2, Cdk1, Ccnb1, and Ccnb2 through the p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Phosphor-in-glass-film (PiG-F) has been extensively investigated, showing great potential for use in laser lighting technique. Thickness is apparently a key parameter for PiG-F, affecting the heat dissipation, absorption, and reabsorption, thus determining the luminous efficacy and luminescence saturation threshold (LST). Conventional studies suggest that thinner films often have lower thermal load than that of the thicker ones. Unexpectedly, we found that the Lu 3 Al 5 O 12 :Ce (LuAG:Ce)-based PiG-F with a moderate thickness (78 μm) yielded the optimal LST of 31.9 W (14.2 W·mm -2 , rather than 28.0 W (12.3 W·mm -2 ) for the thinnest one (56 μm). This unexpected result was further verified by thermal simulations. With the high saturation threshold together with a high luminous efficacy (∼296 lm·W -1 ), an ultrahigh luminous flux of 7178 lm with a luminous exitance of 2930 lm·mm -2 was thus attained. We believe the new, to the best of our knowledge, findings in this study will substantially impact the design principles of phosphors for laser lighting.

Introduction: Chest X-ray (CXR) is used as the standard diagnostic method in lung diseases, especially in pneumonia, but unfortunately, despite the high risk of receiving radiation, it also has a high false negative rate. Therefore, some researchers recommend ultrasound to diagnose pneumonia., Aim: To investigate the accuracy of lung ultrasound compared to CXR for the diagnosis of pneumonia children by meta-analysis method., Material and Methods: Original articles which evaluated accuracy of lung ultrasound compared to chest X-ray for the diagnosis of pneumonia in children, published between 1 January 2010 and 20 March 2021, were identified in the PubMed, Web of Science, Embase, Scopus and Cochrane Library databases. Data synthesis and statistical analysis were carried out using STATA software. Odds ratios with 95% confidence interval (CI), fixed effect model and mean difference with 95% CI, random effect model (REM) were calculated., Results: At the first step, 1016 potentially important research abstracts and titles were discovered in our electronic searches, 8 papers were in agreement with our inclusion criteria. The statistical analysis showed sensitivity of 95.5% (95% CI: 93.6-97.1%) and specificity of 96.3% (95% CI: 92.1-98.4%) for the lung ultrasound, and CXR sensitivity and specificity were 87.4% (95% CI: 84.3-90.0%) and 98.6% (95% CI: 95.8-99.6%), respectively., Conclusions: The present study showed that ultrasound can be useful in diagnosing pneumonia in children, and due to the lack of risk of receiving radiation, this method is even more preferred., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Retinal neovascularization is one of the leading causes of vision loss and a hallmark of proliferative diabetic retinopathy (PDR). The immune system is observed to be involved in the pathogenesis of diabetic retinopathy (DR). The specific immune cell type that contributes to retinal neovascularization can be identified via a bioinformatics analysis of RNA sequencing (RNA-seq) data, known as deconvolution analysis. Previous study has identified the infiltration of macrophages in the retina of rats with hypoxia-induced retinal neovascularization and patients with PDR through a deconvolution algorithm, known as CIBERSORTx. Here, we describe the protocols of using CIBERSORTx to perform the deconvolution analysis and downstream analysis of RNA-seq data., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to explore the effect of Gegen Qinlian Decoction on gut microbiota of irritable bowel syndrome with diarrhea(IBS-D) rats. A total of 36 male SD rats were randomly classified into the control group, model group, rifaximin group(150 mg·kg~(-1)), and high-dose(8.125 g·kg~(-1)), medium-dose(4.062 5 g·kg~(-1)) and low-dose(2.031 3 g·kg~(-1)) Gegen Qinlian Decoction groups with the random number table method, 6 in each group. After modeling, rats were treated for 8 days. The general state, bristol stool chart(BSC) score, and the minimum volume threshold for abdominal withdrawal reflex were recorded. Pathological changes of colon tissues were observed based on hematoxylin and eosin(HE) staining, and gut microbiota was analyzed based on 16 S rRNA sequencing. Compared with the model group, rifaximin group and high-dose and medium-dose Gegen Qinlian Decoction groups showed low BSC score(P&lt;0.01) and high minimum volume threshold for abdominal lifting(P&lt;0.05). HE staining showed that Gegen Qinlian Decoction could relieve intestinal inflammation. 16 S rRNA sequencing suggested obvious variation of gut microbiota in IBS-D rats. Gegen Qinlian Decoction significantly raised the richness index and diversity index of gut microbiota, regulated the number of the flora, and improved alpha diversity and beta diversity. Species composition of gut microbiota and LEfSe analysis showed that Gegen Qinlian Decoction could significantly increase the ratio of Bacteroidota to Firmicutes, elevate the abundance of probiotics such as Clostridia and Lachnospirales, and reduce the abundance of conditional pathogens such as Bacteroidales, and Prevotellaceae. PICRUSt2 analysis indicated that Gegen Qinlian Decoction was mainly related to multiple metabolic pathways such as carbohydrate metabolism and amino acid metabolism. In summary, Gegen Qinlian Decoction can significantly reduce visceral hypersensitivity of IBS-D rats, alleviate intestinal inflammation, and relieve clinical symptoms such as diarrhea. The mechanism is the likelihood that it regulates the composition and structure of gut microbiota and improves its metabolic pathway as well.