Search

Mei-Xiang Zhan,1,2,* Li Tang,3,* Yun-Fei Lu,4,* Huang-Hui Wu,1,* Zhi-Bin Guo,1 Zhong-Mou Shi,1 Chen-Long Yang,1 Yi-Qing Zou,1,2 Fei Yang,1,2,5 Guo-Zhong Chen1,2 1Department of Anesthesiology and Perioperative Medicine, Clinical Medical College, (900 Hospital of the Joint Logistic Support Force), Fujian Medical University, Fuzhou, Fujian, 350025, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, Fujian, 350025, People’s Republic of China; 3Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 4Department of Anesthesiology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 5Laboratory of Pain Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350122, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Zhong Chen; Fei YangDepartment of Anesthesiology and Perioperative Medicine, 900 Hospital of the Joint Logistic Support Force, Fujian Medical University, #156 West 2 nd Ring Road North, Gulou District, Fuzhou, 350025, People’s Republic of ChinaEmail cgzssq2000@sina.com; yangfeimedbrain@outlook.comIntroduction: Ulinastatin, a broad-spectrum serine protease inhibitor, has been widely used to treat various diseases clinically. However, so far, the antinociceptive effect of ulinastatin remains less studied experimentally and the underlying mechanisms of ulinastatin for pain relief remain unclear. This study aimed to find evidence of the analgesic effect of ulinastatin on acute somatic and visceral pain.Methods: The analgesic effect of ulinastatin on acute somatic and visceral pain was evaluated by using formalin and acetic acid-induced writhing test. The analgesic mechanism of ulinastatin was verified by detecting the peripheral inflammatory cell infiltration and spinal glial activation with hematoxylin-eosin (H&E) and immunohistochemistry staining.Results: We found that both of intraperitoneal (i.p.) pre-administration and post-administration of ulinastatin could reduce the total number of flinching and the licking duration following intraplantar formalin injection in a dose-related manner. However, the inhibitory effect of ulinastatin existed only in the second phase (Phase 2) of formalin-induced spontaneous pain response, with no effect in the first phase (Phase 1). The formalin-induced edema and ulcer were also improved by i.p. administration of ulinastatin. Moreover, i.p. administration of ulinastatin was also able to delay the occurrence of acetic acid-induced writhing and reduced the total number of writhes dose-dependently. We further demonstrated that ulinastatin significantly decreased the local inflammatory cell infiltration in injured paw and peritoneum tissue under formalin and acetic acid test separately. The microglial and astrocytic activation in the spinal dorsal horn induced by intraplantar formalin and i.p. acetic acid injection were also dramatically inhibited by i.p. administration of ulinastatin.Conclusion: Our results for the first time provided a new line of evidence showing that ulinastatin could attenuate acute somatic and visceral pain by inhibiting the peripheral and spinal inflammatory reaction.Keywords: Ulinastatin, formalin, somatic pain, visceral pain, inflammation, antinociception

Background: Intravenous (IV) ketamine has been evaluated alongside electroconvulsive therapy (ECT) in addressing major depressive disorder (MDD) or bipolar depression (BD), though the comparative outcomes remain inconclusive. This meta-analysis aimed to provide a systematic assessment of the efficacy, safety, and tolerability of IV ketamine relative to ECT for treating MDD or BD., Methods: Randomized controlled trials (RCTs) comparing IV ketamine and ECT in terms of efficacy, safety, and tolerability for MDD or BD were identified and reviewed. Three independent investigators extracted relevant data, which was synthesized using RevMan 5.3 software under a random effects model., Results: Five RCTs encompassing 664 patients diagnosed with MDD or BD were analyzed. At 24 h post-initial treatment, IV ketamine demonstrated a statistically greater reduction in depressive symptoms compared to ECT (standardized mean difference (SMD) = -0.49, 95 % CI = -0.96 to -0.03, I 2 = 77 %; P = 0.04). However, no significant differences were observed between groups in terms of the study-defined response (risk ratio (RR) = 1.49, 95 % CI = 0.08 to 28.42, I 2 = 0 %; P = 0.79) at 24 h. Similarly, no notable differences were found for depressive symptom improvement (SMD = -0.48, 95 % CI = -2.41 to 1.45, I 2 = 99 %; P = 0.63), the study-defined response (RR = 0.96, 95 % CI: 0.70 to 1.31, I 2 = 75 %; P = 0.79) or remission (RR = 0.91, 95 % CI: 0.45 to 1.82, I 2 = 90 %; P = 0.78) at the end-of-treatment visit. Among the three RCTs (60 %) comparing the neurocognitive outcomes of IV ketamine and ECT through varying test batteries, results were inconsistent. IV ketamine was associated with marked increases in dissociation, blurred vision, dizziness, and diplopia, while ECT led to a significant rise in muscle pain (all Ps < 0.05). Discontinuation rates due to any cause were comparable between both groups (P > 0.05)., Conclusion: IV ketamine demonstrates a faster onset of antidepressant effects compared to ECT, despite both treatments yielding comparable outcomes at the end-of-treatment visit for patients with MDD or BD. However, large-scale RCTs are required to thoroughly evaluate the long-term efficacy and safety of IV ketamine relative to ECT in these populations., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in conducting this study or preparing the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD)., Methods: A systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs)., Results: Five RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2-13%) and the control group (4-21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache., Conclusion: Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Mo, Shi, Huang, Ning, Wu, Yang and Zheng.)

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis . She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.

Background: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro., Aim: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP., Methods: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro , the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups., Results: HP could form biofilms of different degrees in vitro , and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS , Spot , glup (HP1174), NapA , and CagE , and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327 , and HP1489 . Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis., Conclusion: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes., Methods and Results: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets., Conclusions: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals., (© 2024. The Author(s).)

We analyzed multidimensional biodiversity (including species diversity, functional diversity, and phylogenetic diversity) of needle-broadleaf mixed forests of Abies fargesii var. faxoniana-Betula spp. and needleleaf forests of A . fargesii var. faxoniana in the subalpine regions of eastern edge of Qinghai-Tibet Plateau. We measured leaf functional traits including leaf area, leaf thickness, leaf dry matter content, and specific leaf area. The results showed that leaf thickness (0.28 mm) and leaf dry matter content (319.86 mg·g -1 ) in the needle-broadleaf mixed forests were significantly lower than in the needleleaf forest (0.39 mm and 371.33 mg·g -1 , respectively), while specific leaf area (192.74 cm 2 ·g -1 ) was significantly higher (100.91 cm 2 ·g -1 ). Leaf area showed no significant difference between the two forest communities (27.88 and 26.63 cm 2 , respectively). The phylogenetic signals of all leaf functional traits were significant, except for leaf thickness. The phylogenetic structure of the needle-broadleaf mixed forests and needleleaf forest communities tended toward divergence. Shannon diversity index, Simpson diversity index, species richness, functional richness, functional dispersion, Rao's quadratic entropy, and phylogenetic diversity in the needle-broadleaf mixed forests were all significantly higher than in the needleleaf forest, and these indices were significantly positively correlated. Competitive exclusion played a major role in the assembly of subalpine forest communities, and species diversity, functional diversity, and phylogenetic diversity exhibited synchrony.

Objective: To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion. Methods: A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t -test, Mann-Whitney U test, Wilcoxon signed rank test, χ ² test or corrected χ ² test as appropriate. Results: Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P >0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes; t =-2.392, P =0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t =10.604, P< 0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days; t =2.480, P =0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups ( χ ²=0.278, P =0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups ( t =1.607, P =0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups ( t =-1.003, P =0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was ( M (IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences ( Z =-3.937, P< 0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ ²=1.765， P =0.184). Conclusion: 3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia., Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted., Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10)., Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mo, Shi, Yang, Lan, Deng, Huang, Tan, Pridmore, Ungvari, Xiang and Zheng.)

The natural abundance of stable carbon and nitrogen isotopes (δ 13 C and δ 15 N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ 13 C and δ 15 N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ 13 C and δ 15 N of herbs and the driving factors. The results showed that there were significant differences in leaf δ 13 C and δ 15 N values of herbs among different vegetation types, with the highest δ 13 C and δ 15 N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ 13 C and δ 15 N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (N area ), and leaf mass per area were the main drivers of leaf δ 13 C variations of herbs across different vegetation types, while the relative importance of N area and MAT for variation in leaf δ 15 N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ 13 C and δ 15 N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ 13 C and δ 15 N variations in herbs across different vegetation types.

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana . As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.

Osteoporosis is a systemic skeletal disease that seriously endangers the health of middle-aged and older adults. Recently, with the continuous deepening of research, an increasing number of studies have revealed gut microbiota as a potential target for osteoporosis, and the research concept of the gut-bone axis has gradually emerged. Additionally, the intake of dietary nutrients and the adoption of dietary patterns may affect the gut microbiota, and alterations in the gut microbiota might also influence the metabolic status of the host, thus adjusting bone metabolism. Based on the gut-bone axis, dietary intake can also participate in the modulation of bone metabolism by altering abundance, diversity, and composition of gut microbiota. Herein, combined with emerging literatures and relevant studies, this review is aimed to summarize the impacts of different dietary components and patterns on osteoporosis by acting on gut microbiota, as well as underlying mechanisms and proper dietary recommendations.

Background: As an anticancer Chinese herbal medicine, the effective components and mechanism of Actinidia chinensis Planch (ACP, Tengligen) in the treatment of colon cancer are still unclear. In the present study, the integration of network pharmacology, molecular docking, and cell experiments was employed to study the effective mechanism of ACP against colon cancer., Methods: The Venn diagram and STRING database were used to construct the protein-protein interaction network (PPI) of ACP-colon cancer, and further topological analysis was used to obtain the key target genes of ACP in colon cancer. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to visualize the related functions and pathways. Molecular docking between key targets and compounds was determined using software such as AutoDockTools. Finally, the effect of ACP on CT26 cells was observed in vitro., Results: The study identified 40 ACP-colon key targets, including CASP3, CDK2, GSK3B, and PIK3R1. GO and KEGG enrichment analyses found that these genes were involved in 211 biological processes and 92 pathways, among which pathways in cancer, PI3K-Akt, p53, and cell cycle might be the main pathways of ACP against colon cancer. Molecular docking verified that the key components of ACP could stably bind to the corresponding targets. The experimental results showed that ACP could inhibit proliferation, induce apoptosis, and downregulate the phosphorylation of PIK3R1, Akt, and GSK3B in CT26 cells., Conclusion: ACP is an anti-colon cancer herb with multiple components, and involvement of multiple target genes and signaling pathways. ACP can significantly inhibit proliferation and induce apoptosis of colon cancer cells, which may be closely related to the regulation of PI3K/AKT/GSK3B signal transduction., (© 2023. The Author(s).)

Background: G-protein coupled receptors (GPCRs) are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying mechanism., Methods: The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation (BDL) for 21 d or carbon tetrachloride (CCl 4 ) for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription‑polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65's action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated., Results: We found that hepatic macrophages (HMs)-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL- and CCl 4 -induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation (BMT) experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages (BMMs). Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), all of which subsequently promoted the activation of hepatic stellate cells (HSCs) and the damage of hepatocytes (HCs). Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-α and IL-6 via the Gαq-Ca 2+ -JNK/NF-κB pathways, while promoted the expression of TGF-β through the Gαq-Ca 2+ -MLK3-MKK7-JNK pathway. Notably, pharmacological GPR65 inhibition retarded the development of inflammation, HCs injury and fibrosis in vivo., Conclusions: GPR65 is a major regulator that modulates the progression of liver fibrosis. Thus, targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis., (© 2023. The Author(s).)

Exploring the resource limitation of soil microbial metabolism is essential to understand ecosystem functions and processes. However, the spatially divergent patterns and drivers of soil microbial nutrient limitation cha-racteristics in montane ecosystems at small scales, especially at the slope aspect scale, are still unclear. In this study, we measured soil enzyme activities involved in carbon (C), nitrogen (N) and phosphorus (P) cycle and quantified the microbial nutrient limitations by enzyme stoichiometry in two representative mountain sites in subalpine region of western Sichuan, including the sunny and shady slopes with different vegetation types (shrubland and forest, respectively) in Miyaluo of Lixian County, and with the same vegetation type (shrubland) in Yakexia of Heishui County. The results showed that soil enzyme activities and their stoichiometric ratios were significantly different between slope aspects in Miyaluo, while the differences were not significant in Yakexia. The stoichiometry ratio of C-, N- and P-acquiring enzymes on the sunny slope of Miyaluo was 1:0.96:0.92, approaching the 1:1:1 ratio at the global scale, but deviated from 1:1:1 on the shady slope of Miyaluo (1:1.39:0.75) and the different slopes of Yakexia (1:1.09:1.35). There was no significant difference in vector length between slope aspects at both sites, indicating no significant effect of slope aspect on the microbial C limitation. The vector angle was significantly higher on the sunny slope (43.6°) than that on the shady slope (28.7°) in Miyaluo, suggesting that the microorganisms were mainly N-limited. Partial least squares path model showed that the vector angle was mainly directly influenced by the soil nutrient ratios. The vector angle ranged from 50.3° to 51.4°, and did not differ between slope aspects in Yakexia. Therefore, differences in vegetation types between slope aspects drove variations in soil enzyme activity and microbial nutrient limitation through soil properties. It would provide a scientific basis for predicting the spatial pattern of soil enzyme activity and microbial nutrient limitation.

Objective: This meta-analysis of randomized controlled trials (RCTs) evaluated the overall efficacy and safety of bilateral theta-burst stimulation (TBS) as an intervention for patients with mood disorders., Methods: A systematic search (up to December 7, 2022) of RCTs was conducted to address the study aims. A random-effects meta-analysis was performed by including study-defined responses and remission as primary outcomes., Results: Analyses included six RCTs comprising 285 participants with major depressive disorder (MDD) (n = 233) or a depressive episode in the course of bipolar disorder (BD) (n = 52) who had undergone active bilateral TBS (n = 142) versus sham stimulation (n = 143). Active bilateral TBS outperformed sham stimulation with respect to study-defined improvements (55.1 % versus 20.3 %, 4 RCTs, n = 152, 95%CI: 1.63 to 4.39, P < 0.0001; I 2  = 0 %) and remission rates (37.2 % versus 14.3 %, 2 RCTs, n = 85, 95%CI: 1.13 to 5.95, P = 0.02; I 2  = 0 %) in MDD patients but not those with bipolar or unipolar mixed depression. Superiority of active bilateral TBS over sham stimulation was confirmed for improvements in depressive symptoms at post-bilateral TBS assessments and 8-week follow-ups in patients with either MDD or mixed depression (all P < 0.05). Discontinuation rates due to any reason and adverse events (i.e., headache, dizziness) were similar between TBS and sham stimulation groups with MDD or mixed depression (all P > 0.05)., Conclusion: Bilateral TBS targeting the dorsolateral prefrontal cortex (DLPFC) appears to be a well-tolerated form of repetitive transcranial magnetic stimulation (rTMS) that has substantial antidepressant effects, particularly in patients with MDD. Effects of bilateral TBS on bipolar and unipolar mixed depression should be further investigated., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in conducting this study or preparing the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ 2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P <0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P <0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P <0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P <0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.

Antibiotic contamination in drinking water has attracted widespread attention. The pollution condition of six macrolide antibiotics (erythromycin-H 2 [KG-*2/5]O, clarithromycin, oleandomycin, roxithromycin, leucomycin, and tylosin) in two drinking water treatment plants was monitored, and the reaction mechanism of tylosin, a typical macrolide antibiotic, during chlorination disinfection treatment was investigated. The results showed that the six macrolide antibiotics can be widely detected in the drinking water treatment processes; however, their concentrations were generally very low. The concentrations of macrolide antibiotics in the influents and effluents ranged from 0.18 ng·L -1 to 3.97 ng·L -1 and 0.02 ng·L -1 to 1.91 ng·L -1 , respectively. The removal rates of the six macrolides in the drinking water treatment were different, ranging from 18% (oleandomycin) to 100% (erythromycin- H 2 [KG-*2/5]O). The degradation of the six macrolides during chlorination was slow and greatly affected by water quality parameters. The chlorination degradation of tylosin followed the second-order reaction kinetic mode, with the kinetic rate constant of 0.77 L·(mol·s) -1 at pH 7.0. Nine chlorination degradation products of tylosin were detected, and the reaction pathways primarily included tertiary amine hydroxylation, aromatic oxidation, and epoxy addition.

Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different ( P <0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.

Background: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities., Methods: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow., Results: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage., Conclusion: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling., (© 2023. The Author(s).)

Background: Solanum nigrum L. (SNL) (Longkui) is a Chinese herb that can be used to treat colon cancer. The present study explored the components and mechanisms of SNL in treating colon cancer by using network pharmacology and molecular docking., Methods: The components of SNL were collected from the TCMSP, ETCM, HERB, and NPASS databases. Meanwhile, the target proteins of these ingredients were collected/predicted by the TCMSP, SEA, SwissTargetPrediction, and the STITCH databases colon cancer-related target genes were identified from TCGA and GTEx databases. The interaction networks were established via Cytoscape 3.7.2. Gene Ontology and KEGG pathways were enriched by using the David 6.8 online tool. Finally, the binding of key components and targets was verified by molecular docking, and the cellular thermal shift assay (CETSA) was used to detect the efficiency of apigenin and kaempferol binding to the AURKB protein in CT26 cells., Results: A total of 37 SNL components, 796 SNL targets, 5,356 colon cancer genes, and 241 shared targets of SNL and colon cancer were identified. A total of 43 key targets were obtained through topology analysis. These key targets are involved in multiple biological processes, such as signal transduction and response to drug and protein phosphorylation. At the same time, 104 signaling pathways, such as pathways in cancer, human cytomegalovirus infection, and PI3K-Akt signaling pathway, are also involved. The binding of the four key components (i.e., quercetin, apigenin, kaempferol, and luteolin) and the key targets was verified by molecular docking. The CETSA results showed that apigenin and kaempferol were able to bind to the AURKB protein to exert anti-CRC effects., Conclusions: Quercetin, apigenin, kaempferol, and luteolin are the main components of SNL in treating colon cancer. SNL regulates multiple bioprocesses via signaling pathways, such as pathways in cancer, PI3K-Akt, and cell cycle signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Wu, Shi, Qu, Ding and Hu.)

Photosynthetic efficiency under both steady-state and fluctuating light can significantly affect plant growth under naturally fluctuating light conditions. However, the difference in photosynthetic performance between different rose genotypes is little known. This study compared the photosynthetic performance under steady-state and fluctuating light in two modern rose cultivars ( Rose hybrida ), "Orange Reeva" and "Gelato", and an old Chinese rose plant Rosa chinensis cultivar, "Slater's crimson China". The light and CO 2 response curves indicated that they showed similar photosynthetic capacity under steady state. The light-saturated steady-state photosynthesis in these three rose genotypes was mainly limited by biochemistry (60%) rather than diffusional conductance. Under fluctuating light conditions (alternated between 100 and 1500 μmol photons m -2 m -1 every 5 min), stomatal conductance gradually decreased in these three rose genotypes, while mesophyll conductance ( g m ) was maintained stable in Orange Reeva and Gelato but decreased by 23% in R. chinensis , resulting in a stronger loss of CO 2 assimilation under high-light phases in R. chinensis (25%) than in Orange Reeva and Gelato (13%). As a result, the variation in photosynthetic efficiency under fluctuating light among rose cultivars was tightly related to g m . These results highlight the importance of g m in dynamic photosynthesis and provide new traits for improving photosynthetic efficiency in rose cultivars.

Objectives: As a new physical therapeutic technique, magnetic seizure therapy (MST) has established efficacy in the treatment of depression with few cognitive side effects, and thus appears to be a potential alternative to electroconvulsive therapy (ECT). The findings of randomized controlled trials (RCTs) examining the efficacy and safety of MST versus ECT for depression are inconsistent. This systematic review of RCTs was designed with the aim of assessing the safety and efficacy of MST versus ECT for patients with depression., Methods: The WanFang, Chinese Journal Net (CNKI), EMBASE, PubMed, Cochrane Library, and PsycINFO databases were systematically searched by three independent investigators, from their inceptions to July 24, 2021., Results: In total, four RCTs (n = 86) were included and analyzed. Meta-analyses of study-defined response (risk ratio (RR) = 1.36; 95% CI = 0.78 to 2.36; p = 0.28; I 2 = 0%), study-defined remission (RR = 1.17; 95% CI = 0.61 to 2.23; p = 0.64; I 2 = 0%), and the improvement in depressive symptoms (standardized mean difference (SMD) = 0.21; 95% CI = -0.29 to 0.71; p = 0.42; I 2 = 0%) did not present significant differences between MST and ECT. Three RCTs evaluated the cognitive effects of MST compared with ECT using different cognitive measuring tools, but with mixed findings. Only two RCTs reported adverse drug reactions (ADRs), but these lacked specific data. Only one RCT reported discontinuation due to any reason., Conclusions: This preliminary study suggests that MST appears to have a similar antidepressant effect as ECT for depression, but mixed findings on adverse cognitive effects were reported.

Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial-mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs., (© 2023. The Author(s).)

Flatfoot could be divided into flexible flatfoot and rigid flatfoot. Flatfoot with symptoms is called symptomatic flatfoot, surgical treatment is required if conservative treatment is not effective. Subtalar arthroereisis is a minimally invasive procedure which has been used for many years with good results in flexible flatfoot, however, still has many controversial points. Controversial points focus on indications and contraindications, optimal age, subtalar arthroereisis alone or not, efficacy and safety of absorbable material implants, and implant removal. The paper reviewed and summarized the use and controversies of subtalar arthroereisis in symptomatic flatfoot as follows:the best indication for subtalar arthroereisis was pediatric flexible flatfoot syndrome and aged from 10 to 12 years old was optimal age for treatment;tarsal coalitions with flatfoot and adult flatfoot were relative indications. Stiff flatfoot, joint laxity, and subtalar arthritis were contraindications;obesity and neurogenic flexible flatfoot were relative contraindications. The correction ability of subtalar arthroereisis alone was limited, and it's combined with other procedures depending on patient's situation. The safety and efficacy of absorbable material implants had been reported. Routine removal of the implant was not necessary, the main reason of which was tarsal sinus pain.

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT 3 R in RIS-induced pain sensitization was investigated. According to a sequential exploratory experimental strategy, we first calculated the 50% seizure dosage of ropivacaine to be 42.66 mg/kg (95% confidence interval: 40.19-45.28 mg/kg). We showed that RIS induced significant bilateral mechanical pain hypersensitivity that lasted around 5 days, accompanied by an increase in spinal 5-HT. Moreover, RIS considerably protracted postsurgical pain and enhanced formalin-induced spontaneous flinching in the second phase. Depletion of spinal 5-HT with intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT) reduced RIS-induced pain hypersensitivity and prevented the prolonging of postsurgical pain following RIS. Likewise, blocking spinal 5-HT3R by intrathecal administration of ondansetron reversed RIS-induced pain hypersensitivity and attenuated the pronociception of RIS in the formalin test. Our findings revealed that acute RIS led to pain hypersensitivity and had pronociceptive effects on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. Moreover, our data implied that RIS-induced pain sensitization depends on spinal 5-HT/5-HT 3 R signaling. Thus, targeting the descending serotonergic facilitation system should be an important element of the precise treatment for local anesthetic toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Fuzheng Nizeng Decoction (FZNZ) has a history of decades in gastric precancerous lesions (GPL) treatment, which has shown clear clinical efficacy. Blocking GPL is a key measure to reduce the incidence of gastric cancer (GC). Therefore, we aim to investigate the mechanism of FZNZ-induced ferroptosis and endoplasmic reticulum (ER) in MNNG-induced gastric precancerous lesion (MC) cells, which has been rarely studied in Traditional Chinese Medicine (TCM). Methods: First, CCK8 and lactate dehydrogenase assays were conducted to study the potential effect of FZNZ on MC cells. Second, combined transcriptomic and metabolomic analysis were used to explore the effect and mechanism of FZNZ. Functionally, the occurrence of ferroptosis was assessed by transmission electron microscopy morphological observation and measurement of ferrous iron levels, lipid peroxidation, and glutathione levels. Finally, the expression levels of mRNAs or proteins related to ferroptosis and ER stress were determined by qPCR or western blot assays, respectively. Results: FZNZ inhibited MC cells viability and induced cell death. By metabolomics coupled with transcriptomics analysis, we found that the mechanism of FZNZ treatment induced ferroptosis and was related to glutathione metabolism and ER stress. We then, for the first time, found that FZNZ induced ferroptosis, which contributed to an increase in intracellular ferrous iron, reactive oxygen species, and malondialdehyde and a decrease in glutathione. Meanwhile, the protein level of glutathione peroxidase 4 (GPX4) was decreased. The mRNA levels of ATF3/CHOP/CHAC1, which are related to ferroptosis and ER stress, were also upregulated. Conclusion: Our results elaborate that FZNZ could induce ferroptosis and ER stress in MC cells, and reduce GPX4/GSH. ATF3/CHOP/CHAC1 may play a crosstalk role, which provides a new molecular mechanism for the treatment of GPL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chu, Wang, Jia, Yang, Shi, Cui, Huang, Ye and Zhang.)

Predicting the groundwater level of karst aquifers in North China Coalfield is essential for early warning of mine water hazards and regional water resources management. However, the dynamic changes of strata structure and hydrogeological parameters driven by coal mining activity cause challenges to the process-oriented groundwater model. In order to achieve accurate prediction of groundwater level in large mining areas, this study was the first to use the data-driven Nonlinear Autoregressive with External Input (NARX) model to predict the groundwater level of six karst aquifer observation wells in Pingshuo Mining Area. Three variable input scenarios were set up, solely considering meteorological factors, anthropogenic disturbance factors, and considering both meteorological and anthropogenic disturbance factors. The novel partial mutual information (PMI) screening algorithm was adopted to determine optimized input variables in each scenario. The input and feedback delay coefficients of NARX model were determined by using Seasonal-trend Decomposition Procedure Based on Loess (STL) algorithm and auto- and cross-correlation functions. The results showed that PMI algorithm can effectively screen out the optimal input variables for predicting groundwater level, the NSE coefficients of the PMI-NARX models under the three scenarios were 38.81%, 4.26% and 41.46% higher than those of the corresponding control experiments, respectively. In addition, the prediction performance of the PMI-NARX built on the basis of meteorological factors is poor (NSE <0.63). However, in scenarios which solely use anthropogenic disturbance factors and both use meteorological and anthropogenic disturbance factors, the PMI-NARX coupling models exhibit good prediction performance (NSE and R 2 are all greater than 0.8). Especially under solely considering anthropogenic disturbance factors scenario, the model still exhibited good prediction accuracy with a negligible number of input variables. The results can provide technical and theoretical support for the prediction of groundwater level in other mining areas., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To explore early efficacy of minimally invasive Chevron Akin(MICA) osteotomy for the treatment of mild to moderate hallux valgus., Methods: From June 2019 to April 2021, a total of 26 patients (29 feet) with mild to moderate hallux valgus, including 1 male and 25 females aged from 19 to 78 years old with an average of(38.3±19.5) years old, were treated with MICA. Preoperative and postoperative hallux valgus angle(HVA), intermetatarsal angle(IMA) and shortening of the first metatarsal were observed and compared. American Orthopedic Foot and Ankle Society (AOFAS) forefoot scoring system and visual analogue scale (VAS) were applied to evaluate clinical outcome at the final follow-up, and complications were also recorded., Results: All patients obtained followed up from 12 to 33 months with an average of(19.6±5.1) months. HVA and IMA was improved from (32.3±6.6)° and (11.7±3.2)° pre-operatively to (13.0±5.3)° and (6.1±3.2)° post-operatively, respectively, which had a significant difference ( P <0.01). The average shortening of the first metatarsal was (2.7±1.1) mm. AOFAS and VAS was improved from (55.7±7.4) and (6.5±1.5) preoperatively and to (88.5±7.9) and (0.7±0.4) respectively at the final follow-up, which also had a significant difference( P <0.01). According to AOFAS score, 15 feet achieved an excellent result, 11 good and 3 moderate., Conclusion: MICA osteotomy is a safe and reliable surgical technique for mild to moderate hallux valgus with advantages of minimally invasive, rapid recovery, low complication rate and an effect improvement of hallux valgus deformity.

Recurrence of hallux valgus is one of the most common and difficult complications after surgery. Due to the lack of understanding of 3D deformity of hallux valgus and risk factors for recurrence, the overall recurrence rate is still high, and the choice of treatment is still controversial. Improper operation and severe deformity are known risk factors for recurrence, while the role of unstable of the first plantar train and combined flat foot deformity in the recurrence has been paid more attention by scholars at home and abroad. In addition to the first metatarsophalangeal fusion, modified Lapidus osteotomy and proximal metatarsal osteotomy have been proven to be reliable revision procedures. The purpose of this study is to summarize risk factors for recurrence of hallux valgus after surgery, and to explore the choice of revision surgery after recurrence, in order to provide guidance for prevention and management of recurrence of hallux valgus.

The expert consensus of the third-generation minimally invasive technical specification for hallux valgus was developed by Foot and Ankle Committee of Orthopaedic Branch of Chinese Medical Doctor Association, Foot and Ankle Committee of Sports Medicine Branch of Chinese Medical Doctor Association, and Foot and Ankle Expert Committee of Orthopedic Branch of Chinese Association of Integrative Medicine. The consensus was drawn from evidence-based medicine and experts' clinical experience to provide an academic guidance of the third-generation minimally invasive technical specification of hallux valgus for the orthopedic surgeons, including definition, indications, osteotomy techniques, post-operative rehabilitation and prognosis.

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G-J ( 1 - 4 ), and five known analogs ( 5 - 9 ) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1 - 9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD 50 values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).

Objective: To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome., Methods: From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH)., Results: All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 ( P <0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 ( P <0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence., Conclusion: Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.

The Qinglong Area of Tianfu New District in China is the connection area of Chengdu city, Sichuan Province, which dominantly supports the primary agricultural products for the metropolis. The soil quality, therefore, has been deteriorating in recent decades due to the intensive planting and industrial pollution. Thus, the evaluation of soil quality and the identification of the pollution sources are significant for sustainable soil planting and regulation. To this end, 395 soil samples were collected, and the parameters of pH, soil organic matter (SOM), total potassium (TK), available potassium (AK), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), total phosphorus (TP), available phosphorus (AP), Se, B, V, Zn, Mn, Mo, Ni, Co, As, Cd, Cr, Cu, Hg, and Pb were analyzed. The results revealed that TN, Se, Hg, and TP were obviously higher than the background value of the Chengdu Economic Zone, and the Cr, Mn, pH, and TK were depleted. The combination of correlation statistics, geostatistics, and positive matrix factorization (PMF) source analysis revealed that heavy metal enrichments were mainly affected by four sources, namely natural sources (32%)>industrial sources (30%)>agricultural sources (25%)>traffic sources (14%). Likewise, the source apportionments were verified regarding topography, industrial boundary, farmer density, and traffic flow. It was estimated that Mo, Co, Ni, and V were affected by slope; the enrichment of Hg and As was the result of agricultural activities; Cd, Mn, Cr, and Zn were affected by industrial waste diffusion; and Pb, Zn, Cu, Cd, and Hg were related to transportation. To a certain extent, agricultural fertilization and pesticide application have partially controlled soil fertility and pollution (Hg and As).

Objectives: Patients with advanced ampullary carcinoma (AC) who are unsuitable for surgery are most likely to have poor outcomes. The role of endoscopic radiofrequency ablation (RFA) in this population has not been fully defined. We aimed to assess the short- and long-term outcomes of RFA in a large cohort of AC patients., Methods: In this retrospective study, data of consecutive patients with pathologically proven AC who underwent successful endobiliary RFA and/or stent placement were collected. All patients did not undergo surgical resection. The primary outcome was overall survival (OS). The secondary outcomes included clinical success and adverse events., Results: A total of 85 patients, 50 in the RFA plus stenting group and 35 in the stenting alone group, were identified. The median OS was significantly longer in the RFA group than in the stenting alone group (16.9 vs. 9.8 months, P < 0.001). In multivariable Cox analysis, RFA (hazards ratio 0.408; 95% confidence interval 0.235-0.706; P = 0.001) was the only independent OS predictor. Eight patients with stage II tumors, exclusively from the RFA group, survived for more than 3 years. Clinical success was comparable between the two groups (96% vs. 100%, P = 0.231). Early adverse events between the two groups were similar (10% vs. 2.9%, P = 0.206); however, late biliary/pancreatic stenoses occurred in three RFA patients who were successfully managed with endoscopic interventions., Conclusions: Endoscopic RFA appears to prolong patients' survival with acceptable safety; it may therefore be a feasible treatment option for patients with inoperable ampullary cancers., (© 2021 Japan Gastroenterological Endoscopy Society.)

The efficacy and safety of adjunctive nonconvulsive electrotherapy (NET) for patients with depression are undetermined. This systematic review was conducted to examine the efficacy and safety of adjunctive NET for patients with depression. Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO and the Cochrane Library) databases were systematically searched from their inception until Jan 27, 2021 by three independent investigators. One randomized controlled trial (RCT) with 3 treatment arms (n = 108) and two observational studies (single-group, before-after design, n = 31) were included. In the RCT, the antidepressant efficacy of NET on depression was similar to that of electroconvulsive therapy (ECT) (P > 0.05) but with significantly fewer neurocognitive impairments as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (P < 0.05). In two observational studies, the 17-item Hamilton Depression Rating Scale (HAMD-17) scores decreased significantly from baseline to post-NET (all Ps < 0.05), without adverse neurocognitive effects. In the RCT, adverse drug reactions (ADRs) were not separately reported among the 3 treatment arms but a similar rate of discontinuation was reported. The currently available limited evidence from 3 studies suggests that NET as an adjunctive treatment may be a safe, well-tolerated, effective therapy for depression without serious neurocognitive impairments., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ulinastatin is a broad-spectrum protease inhibitor widely used for the treatment of various inflammation-related diseases owing to its recognized excellent anti-inflammatory and cytoprotective properties. However, whether ulinastatin can relieve postoperative pain remains unclear. In this study, we evaluated the analgesic effects of ulinastatin administered either as a single agent or in combination with sufentanil in a validated preclinical rat model of postoperative pain induced by plantar incision. We found that incisional surgery on the hind paw of these rats induced sustained ipsilateral mechanical pain hypersensitivity that lasted for at least 10 days. A single intraperitoneal (i.p.) injection of ulinastatin prevented the development and reversed the maintenance of incision-induced mechanical pain hypersensitivity in a dose-dependent manner. However, ulinastatin had no effect on the baseline nociceptive threshold. Moreover, repeated i.p. injections of ulinastatin persistently attenuated incision-induced mechanical pain hypersensitivity and promoted recovery from the surgery. The rats did not develop any analgesic tolerance over the course of repeated injections of ulinastatin. A single i.p. injection of ulinastatin was also sufficient to inhibit the initiation and maintenance of incision-induced hyperalgesic priming when the rats were subsequently challenged with an ipsilateral intraplantar prostaglandin E2 injection. Furthermore, the combined administration of ulinastatin and sufentanil significantly enhanced the analgesic effect of sufentanil on postoperative pain, which involved mechanisms other than a direct influence on opioid receptors. These findings demonstrated that ulinastatin had a significant analgesic effect on postoperative pain and might be a novel pharmacotherapeutic agent for managing postoperative pain either alone or as an adjuvant., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate associations between mental distress and COVID-19-related changes in behavioral outcomes and potential modifiers (age, gender, educational attainment) of such associations., Study Design: This was a cross-sectional study., Methods: An online survey using anonymous network sampling was conducted in China from April to May 2020 using a 74-item questionnaire. A national sample of 10,545 adults in 31 provinces provided data on sociodemographic characteristics, COVID-19-related mental distress, and changes in behavioral outcomes. Structural equation models were used for data analyses., Results: After adjusting for covariates, greater mental distress was associated with increased smoking (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.20-1.68 and OR = 1.54, 95% CI: 1.31-1.82 per one standard deviation [SD] increase in mental distress) and alcohol consumption (OR = 1.67, 95% CI: 1.45-1.92 and OR = 1.47, 95% CI: 1.24-1.75 per one SD increase in mental distress) among current smokers and drinkers and with both increased and decreased physical activity (ORs ranged from 1.32 to 1.56). Underweight adults were more likely to lose body weight (≥1 kg; OR = 1.63, 95% CI: 1.30-2.04), whereas overweight adults were more likely to gain weight (OR = 1.61, 95% CI: 1.46-1.78) by the same amount. Association between mental distress and change in physical activity was stronger in adults aged ≥40 years (ORs ranged from 1.43 to 2.05) and those with high education (ORs ranged from 1.43 to 1.77). Mental distress was associated with increased smoking in males (OR = 1.60, 95% CI: 1.37-1.87) but not females (OR = 1.11, 95% CI: 0.82-1.51)., Conclusions: Greater mental distress was associated with some positive and negative changes in behavioral outcomes during the pandemic. These findings inform the design of tailored public health interventions aimed to mitigate long-term negative consequences of mental distress on outcomes., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Understanding the changes of natural abundance of stable carbon and nitrogen isotopes (δ 13 C and δ 15 N) along soil profile is of great importance in revealing the mechanisms of soil carbon and nitrogen cycling in terrestrial ecosystems. Based on a comprehensive review on the distribution of δ 13 C and δ 15 N along soil profile, the mechanisms underlying their vertical distribution were mainly introduced here. There were three mechanisms driving the δ 13 C vertical distribution in soil profile: 1) historical changes of vegetation δ 13 C value, 2) changes of C3-C4 species dominance in plant communities, 3) accumulation of 13 C-enriched microbial-derived carbon during decomposition. The effects of 13 C Suess effect on the vertical distribution of δ 13 C in soil profile were also discussed. There were four mechanisms underlying the vertical distribution of δ 15 N in soil profile: 1) 15 N-depletion gas loss during denitrification, 2) accumulation of 15 N-enriched microbial-derived nitrogen during decomposition, 3) accumulation of 15 N-encriched mycorrhizal fungi residues in deep soil as a result of transferring 15 N-depleted nitrogen compounds to plants by mycorrhizae, 4) intera-ction between soil organic matter and mineral substance. We proposed important concerning points for the future study on vertical distribution of natural abundance of stable carbon and nitrogen isotopes in soil profile.

Purpose: Glioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated., Methods: Quantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, in situ tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137., Results: We found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3'-UTR region partly restored the effects of miR-137 in vitro and in vivo . Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM., Conclusions: These findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chen, Wei, Wei, Yin, He, Ge and Shi.)

The development of resistance to EGFR Tyrosine kinase inhibitors (TKIs) in NSCLC with activating EGFR mutations is a critical limitation of this therapy. In addition to genetic alterations such as EGFR secondary mutation causing EGFR-TKI resistance, compensatory activation of signaling pathways without interruption of genome integrity remains to be defined. In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. Taken together, we present evidence for the reversal of resistance to EGFR TKI by the addition of small molecule S6K1/MDM2 antagonists that could have clinical benefit.

Objective: China launched its health reform in 2009. This study aimed to assess changes in preventive care utilisation (PCU) and its relationship with the healthcare reform., Design: A cross-sectional study using demographic characteristics, socioeconomic status, environmental factors, and lifestyle and health status data of adults from five waves (2004-2015) of the China Health and Nutrition Survey (CHNS) was conducted. Multilevel mixed-effects logistic regression models were used., Setting: Data were derived from urban and rural communities of nine provinces in China., Participants: Data were obtained from five waves of the CHNS, with 9960 participants in 2004, 9888 in 2006, 10 286 in 2009, 9709 in 2011, and 10 628 in 2015., Outcome: The primary outcome was PCU., Results: PCU in 2004-2015 among adults was 3.29%, 3.13%, 3.77%, 4.95% and 2.73%, respectively. Whether before or after the health reform, having a history of disease and female gender were positive influencing factors of PCU. Before 2009, PCU was significantly associated with gender, income, medical insurance status and region. Age, medical insurance status, history of drinking and education level significantly affected PCU in 2009-2011. Having medical insurance was no longer a positive influencing factor of PCU, while high income had a negative effect on PCU, in 2011-2015., Conclusions: PCU from 2004 to 2015 was low and the health reform in China may lack sustainable effect on PCU. Further studies on how to ensure sustainability of PCU are necessary, and further reforms on preventive care services should be aimed at different ages, rural areas and participants without history of disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)