Sirt7/HIC1 complex participates in hyperglycaemia-mediated EndMT via modulation of SDC1 expression in diabetic kidney disease and metabolic memory.

Diabetic kidney disease (DKD), a primary microvascular complication arising from diabetes, may result in end-stage renal disease. Epigenetic regulation of endothelial mesenchymal transition (EndMT) has been recently reported to exert function in metabolic memory and DKD. Here, we investigated the mechanism which Sirt7 modulated EndMT in human glomerular endothelial cells (HGECs) in the occurrence of metabolic memory in DKD. Lower levels of SDC1 and Sirt7 were noted in the glomeruli of both DKD patients and diabetes-induced renal injury rats, as well as in human glomerular endothelial cells (HGECs) with high blood sugar. Endothelial-to-mesenchymal transition (EndMT) was sustained despite the normalization of glycaemic control. We also found that Sirt7 overexpression associated with glucose normalization promoted the SDC1 expression and reversed EndMT in HGECs. Furthermore, the sh-Sirt7-mediated EndMT could be reversed by SDC1 overexpression. The ChIP assay revealed enrichment of Sirt7 and H3K18ac in the SDC1 promoter region. Furthermore, hypermethylated in cancer 1 (HIC1) was found to be associated with Sirt7. Overexpression of HIC1 with normoglycaemia reversed high glucose-mediated EndMT in HGECs. The knockdown of HIC1-mediated EndMT was reversed by SDC1 upregulation. In addition, the enrichment of HIC1 and Sirt7 was observed in the same promoter region of SDC1. The overexpressed Sirt7 reversed EndMT and improved renal function in insulin-treated diabetic models. This study demonstrated that the hyperglycaemia-mediated interaction between Sirt7 and HIC1 exerts a role in the metabolic memory in DKD by inactivating SDC1 transcription and mediating EndMT despite glucose normalization in HGECs.

Study on the mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in sedation and tranquillising mind.

This study analysed the pharmacological mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in sedation and tranquillising mind using network pharmacology methods. The findings of this study aimed to serve as a reference for the development of novel drugs and the clinical expansion and application of traditional Chinese medicine formulas. The chemical constituents and therapeutic targets of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen were acquired from TCMSP, HERB, and ETCM databases. Active components were identified using ADME criteria, while the primary targets associated with sedation and mental tranquillity were obtained from GENECARDS, OMIM, and DRUGBANK databases. A protein-protein interaction (PPI) network analysis was conducted using the STRING platform to investigate potential functional protein modules by the network. The METASCAPE platform was employed for the study of the "component-target" and its associated biological processes and pathways. Subsequently, the "component-target" network was constructed using Cytoscape 3.9.1 software. Finally, the validation of molecular docking was conducted through AUTODOCK. The findings revealed that Quercetin, Atropine, Dauricine, (S)-Coclaurine, and other active ingredients were identified as the core constituents of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. Additionally, PTGS2, PTGS1, MAOB, GABRA1, SLC6A2, ADRB2, CHRM1, HTR2A, and other targets were identified as the core targets. The results of the molecular docking analysis demonstrated that Quercetin, Atropine, Dauricine, and (S)-Coclaurine exhibited binding solid affinity towards PTGS2 and PTGS1. The predominant biological pathways associated with sedation and tranquilisation primarily involved Neuroactive ligand-receptor interaction and activation of receptors involved in chemical carcinogenesis. This study provided initial findings on the multi-component, multi-target, and multi-pathway mechanism underlying the sedative and tranquillising effects of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen. These findings had the potential to serve as a foundation for the future development and utilisation of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen.

The TOFr of 0.75 to 0.85 is the optimal timing for IONM during thyroid surgery: a prospective observational cohort study.

BACKGROUD: Recurrent laryngeal nerve (RLN) injury is one of the serious complications of thyroid tumour surgery, surgical treatment of thyroid cancer requires careful consideration of the RLN and its impact on glottis function. There has been no unified standard for precise neuromuscular block monitoring to guide the monitoring of RLN in thyroid surgery. This study aimed to investigate the correlation between Train-of-four stabilization ratio (TOFr) and neural signal values of intraoperative neurophysiological monitoring (INOM) during thyroid operation, and further to determine the optimal timing for INOM during thyroid operation. METHODS: Patients scheduled for thyroid tumour resection with INOM and RLN monitoring from April 2018 to July 2018 in our center were recruited. Electromyography (EMG) signals and corresponding TOFr were collected. All nerve stimulation data were included in group VR. Vagus nerve stimulation data were included in Subgroup V. RLN stimulation data were included in Subgroup R. The timing of recording was as follows: Vagus nerve EMG amplitude after opening the lateral space between the thyroid and carotid sheath and before the initiation of thyroid dissection, RLN EMG amplitude at first recognition, RLN EMG amplitude after complete thyroid dissection (Repeat three times), and Vagus nerve EMG amplitude after resection of the thyroid (Repeat three times). Correlation analysis of continuous variables was described by a scatter diagram. Pearson correlation analysis or Spearman correlation analysis was used for the two groups of variables. RESULTS: Finally, 134 vagus nerve signals and 143 RLN signals were analysed after matching with TOFr. The EMG amplitude in the VR group and subgroups after nerve stimulation was positively correlated with TOFr (p < 0.05). In the VR, V and R group, the incidence of EMG ≥ 500 µV in the 0.75 < TOFr ≤ 0.85 interval was significantly higher than the 0 < TOFr ≤ 0.75 interval (P = 0.002, P = 0.013 and P = 0.029), and has no statistical difference compared to 0.85 < TOFr ≤ 0.95 interval (P > 0.05). CONCLUSIONS: The EMG signals of the RLN and vagus nerve stimulation during thyroid surgery were positively correlated with TOFr. TOFr > 0.75 could reflect more than 50% of the effective nerve electrophysiological signals, 0.75 < TOFr ≤ 0.85 interval was the optimal timing for IONM during thyroid surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800015797) Registered on 20/04/2018. https://www.chictr.org.cn .

Incidence of postoperative hypothermia and shivering and risk factors in patients undergoing malignant tumor surgery: a retrospective study.

BACKGROUND: Perioperative hypothermia and shivering are common and can cause adverse outcomes. The aim of this study was to investigate the incidence of postoperative hypothermia and shivering and their risk factors in patients undergoing malignant tumor surgery. METHODS: This retrospective study collected data from patients with American Society of Anesthesiologists physical status (ASA) I or II who underwent scheduled surgery from November 2020 to March 2021 at Fudan University Shanghai Cancer Center. Each patient's core body temperature was measured at three time points: time point 1 (arrival at the postanesthesia care unit (PACU)), time point 2 (after 30-min care in the PACU), and time point 3 (at discharge from the PACU). At time point 1, if the patient's body temperature was below 36 ℃, we provided an active forced-air warmer. At time point 2, if it was still below 36 ℃, the forced-air warmer was still applied until the patient was discharged from the PACU. If it reached 36 ℃, the forced-air warmer would be switched off. Univariate and multivariate logistic regression combined with stepwise methods and linear regression were used to explore risk factors for postoperative hypothermia and shivering. RESULTS: The numbers (percentage) of 202 patients who developed postoperative hypothermia at the different time points were 52 (25.7%), 37 (18.3%) and 28 (13.9%). Eight patients (4.0%) experienced shivering. Multivariate logistic regression showed that high weight (OR = 0.923, 95% CI: 0.884 to 0.964, P = 0.0003) and low estimated blood loss (OR = 0.252, 95% CI: 0.115 to 0.550, P = 0.0005) were protective factors against hypothermia, while long surgical duration (OR = 3.339, 95% CI: 1.675 to 6.655, P = 0.0006) was an independent risk factor for hypothermia at time point 1. There was no risk factor associated with the occurrence of shivering (P > 0.05). There was a significant difference between the hypothermia and normothermia groups in the median length of stay in the PACU (59.0 vs. 49.0 min, P = 0.0123). CONCLUSIONS: Postoperative hypothermia occurred frequently. Weight, estimated blood loss and surgical duration were significantly associated with hypothermia on arrival at the PACU.

Mechanisms of interaction between metal-organic framework-based material and persulfate in degradation of organic contaminants (OCs): Activation, reactive oxygen generation, conversion, and oxidation.

Metal-organic frameworks (MOFs)-based materials have been of great public interest in persulfate (PS)-based catalytic oxidation for wastewater purification, because of their excellent performance and selectiveness in organic contaminants (OCs) removal in complex water environments. The formation, fountainhead and reaction mechanism of reactive oxygen species (ROSs) in PS-based catalytic oxidation are crucial for understanding the principles of PS activation and the degradation mechanism of OCs. In the paper, we presented the quantitative structure-activity relationship (QSAR) of MOFs-based materials for PS activation, including the relationship of structure and removal efficiency, active sites and ROSs as well as OCs. In various MOFs-based materials, there are many factors will affect their performances. We discussed how various surface modification projects affected the characteristics of MOFs-based materials used in PS activation. Moreover, we revealed the process of ROSs generation by active sites and the oxidation of OCs by ROSs from the micro level. At the end of this review, we putted forward an outlook on the development trends and faced challenges of MOFs for PS-based catalytic oxidation. Generally, this review aims to clarify the formation mechanisms of ROSs via the active sites on the MOFs and the reaction mechanism between ROSs and OCs, which is helpful for reader to better understand the QSAR in various MOFs/PS systems.

The Dynamic Accumulation Rules of Chemical Components during the Medicine Formation Period of Angelica sinensis and Chemometric Classifying Analysis for Different Bolting Times Using ATR-FTIR.

The dried roots of the perennial herb Angelica sinensis (Oliv.) Diels (AS) are commonly used as medicinal and edible resources. In commercial planting, early bolting and flowering (EB) of ca. 60% in the medicine formation period reduces root yield and quality, becoming a significant bottleneck in agricultural production. In the cultivation process, summer bolting (SB) occurs from June to July, and autumn bolting (AB) occurs in September. The AB root is often mistaken for the AS root due to its similar morphological characteristics. Few studies have involved whether the root of AB could be used as herbal medicine. This study explored and compared the accumulation dynamics of primary and secondary metabolites in AS and EB roots during the vegetative growth stage (from May to September) by light microscopy, ultraviolet spectrometry, and HPLC methods. Under a microscope, the amount of free starch granules and oil chamber in the AS root increased. On the contrary, they decreased further from EB-Jul to EB-Sep. By comparison, the wall of the xylem vessel was slightly thickened and stacked, and the cell walls of parenchyma and root cortex tissue were thickened in the EB root. Early underground bolting reduces soluble sugar, soluble protein, free amino acids, total C element, total N element, ferulic acid, and ligustilide accumulation, accompanied by the lignification of the root during the vegetative growth stage. Furthermore, a total of 55 root samples from different bolting types of AS root (29 samples), SB root (14 samples), and AB root (12 samples) were collected from Gansu Province during the harvesting period (October). The later the bolting occurred, the less difference there was between unbolted and bolted roots in terms of morphological appearance and efficacy components. Fourier transform infrared spectroscopy with the attenuated total reflection mode (ATR-FTIR) provides a "holistic" spectroscopic fingerprinting of all compositions in the tested sample. The ATR-FTIR spectrum of the AB root was similar to that of the AS root. However, the number and location of absorption peaks in the spectra of SB were different, and only one strong absorption peak at 1021 cm-1 was regarded as the characteristic peak of C-O stretching vibration in lignin. The ATR-FTIR spectra can be effectively differentiated based on their various characteristics using orthogonal partial least squares discrimination analysis (OPLS-DA). Results were assessed using multiple statistical techniques, including Spearman's correlation, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and OPLS-DA. Among these methods, the ATR-FTIR data demonstrated the most effective outcomes in differentiating between viable and non-viable roots for their application in herbal medicine. Essential substances are ferulic acid and flavonoid, which are much more abundant in the AB root. It provides a material basis for the pharmacological action of the AB roots and a theoretical basis for improving their availability.

Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer: a mechanistic, multicentre randomised clinical trial.

BACKGROUND: Intravenous lidocaine has been postulated to improve long-term survival after surgery for pancreatic cancer through anti-inflammatory effects, anti-tumour effects, or both. We investigated whether intraoperative lidocaine improves survival after pancreatectomy for pancreatic cancer and whether lidocaine modified the formation of neutrophil extracellular traps (NETs), high levels of which are associated with poor prognosis. METHODS: Patients undergoing pancreatectomy were randomly assigned to i.v. lidocaine (continuous intraoperative infusion of 2 mg kg-1 h-1, after 1.5 mg kg-1 bolus at induction of anaesthesia) or saline placebo. The co-primary outcomes were survival/disease-free survival 3 yr after surgery. Secondary outcomes (masked to treatment allocation) included intraoperative opioid (sufentanil) dose, postoperative complications, and circulating and tumour-associated NETs (immunofluorescence assay, enzyme-linked immune assay, or both). RESULTS: A total of 563 participants (34.6% female; median age, 64 yr) completed 3 yr of clinical follow-up. Overall, 283 participants were randomised to lidocaine infusion, and 280 participants were randomised to placebo. Infusion of lidocaine did not alter overall (hazard ratio [HR]=0.98; 95% confidence interval [CI], 0.81-1.17; P=0.79) or disease-free survival (HR=0.91; 95% CI, 0.71-1.17; P=0.44). Mean intraoperative sufentanil dose was reduced by lidocaine infusion (47.6 µg [4.6]) compared with placebo (68.4 µg [4.8]; P<0.001), but postoperative complications and length of hospital stay were similar between groups. Circulating NETs were lower after lidocaine infusion up to 3 days after surgery, but tumour-associated NETs were not altered by intraoperative treatment. CONCLUSION: In patients undergoing pancreatectomy for pancreatic cancer, intraoperative infusion of lidocaine did not improve overall or disease-free survival. Reduced formation of circulating NETs was absent in pancreatic tumour tissue. CLINICAL TRIAL REGISTRATION: NCT03245346; updated in Chi-CTR-2000035469.

Propofol protects against high glucose-mediated endothelial injury via inhibition of COX2 and iNOS expressions.

Perioperative hyperglycemia is a common metabolic disorder in the clinic. Hyperglycemia, via upregulation of E74-like ETS transcription factor 3 (ELF3), induces cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expressions, thus leading to endothelial apoptosis and vascular endothelial injury. Propofol is a widely used anesthetic. In the present study, we explored whether and how propofol protects against high glucose-induced COX2 and iNOS expressions in human umbilical vein endothelial cells (HUVECs). We found that high glucose level decreases cell viability and increases COX2 and iNOS expressions in HUVECs. Our data also indicated that ELF3 overexpression participates in high glucose-mediated cell viability reduction and high glucose-induced COX2 and iNOS expressions. Moreover, propofol treatment improves high glucose-mediated reduction in cell viability and decreases COX2 and iNOS expressions via inhibition of ELF3 expressions. Furthermore, specificity protein 1 (SP1) was found to regulate ELF3 expression, thus mediating endothelial injury. Propofol inhibits high glucose-induced SP1 expression. High glucose increases the abundance of SP1 bound to the ELF3 promoter, which can be reversed by propofol treatment. The protective effect of propofol is reversed by SP1 overexpression. In conclusion, propofol downregulates high glucose-induced SP1 expression, thus attenuating high glucose-induced ELF3 expression, inhibiting high glucose-induced COX2 and iNOS expressions, and improving high glucose-mediated cell viability reduction in HUVECs.

MOR promotes epithelial-mesenchymal transition and proliferation via PI3K/AKT signaling pathway in human colorectal cancer.

The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is implicated in progression and long-term outcome of several types of tumors. However, the expression and clinical significance of MOR in colorectal cancer (CRC) remain unclear. In this study, a total of 180 paraffin-embedded samples of paired tumors and normal tissues from CRC patients are used to explore expression levels of MOR by immunohistochemistry (IHC). Results show that MOR is highly expressed in tumors compared with that in paired normal tissues ( P<0.0001). MOR expression levels are associated with the degree of differentiation ( P<0.001) and the regional lymph node metastasis ( P<0.001). In addition, a significant difference is also found in the overall survival (OS) between MOR low- and high-expression groups ( P=0.002), especially in patients with TNM stage III or IV CRC ( P=0.007). Both univariate ( P=0.002) and multivariate ( P=0.013) analyses indicated that MOR is an independent risk factor associated with CRC prognosis. We further investigate the mechanism in MOR-positive CRC cell line HCT116. The results show that silencing of MOR significantly suppresses epithelial-mesenchymal transition (EMT), in addition to suppressing cell proliferation, migration, and invasion. In addition, the expression of downstream p-AKT is also significantly downregulated, and the above suppression effect could be rescued by PI3K/AKT signaling agonist. We conclude that MOR mediates EMT via PI3K/AKT signaling, facilitating lymph node metastasis and resulting in poor survival of CRC patients. Our findings suggest that MOR is a novel prognostic indicator and the application of opioid receptor antagonists may be a novel therapeutic strategy for CRC patients with high MOR expression.

Impact of perioperative red blood cell transfusion on postoperative recovery and long-term outcome in patients undergoing surgery for ovarian cancer: A propensity score-matched analysis.

BACKGROUND: The impact of perioperative red blood cell transfusion (PRBCT) on cancer survival has remained controversial. METHODS: We conducted a retrospective study in patients undergoing primary debulking surgery (PDS) for ovarian cancer between January 2013 and December 2017. The patients were divided into two groups based on whether they received PRBCT. Clinical characteristics were compared between groups. After propensity score matching, perioperative systemic inflammation-based scores, quality of recovery, postoperative outcomes, disease-free survival (DFS), and overall survival (OS) were compared between groups. Univariate and multivariable Cox proportional hazard models were used to evaluate the association between covariates and survival outcomes. RESULTS: A total of 1037 patients were enrolled in this study, and 31.7% of patients received PRBCT. After propensity matching, there was no significant difference in the clinical characteristics between groups. Patients receiving PRBCT had more postoperative fluctuations in systemic inflammatory response-related indicators (P < 0.001), a higher incidence of postoperative grade II complications (28.4% vs. 14.8%), a longer length of stay (10.6 d vs. 6.2 d) and higher 30-day and total readmission rates (7.1% vs. 4.4% and 11.2% vs. 8.1%, P < 0.001, respectively) than patients who did not receive PRBCT. The OS and DFS rates 3 years after surgery were significantly lower in the patients receiving PRBCT than in patients not receiving PRBCT (58.9% vs. 74.5%, 39.6% vs. 52.3%). CONCLUSIONS: PRBCT was significantly associated with more fluctuations in systemic inflammatory indicators, a prolonged length of stay, higher postoperative complication rates and increased cancer recurrence and overall mortality in ovarian cancer patients undergoing PDS.

Increased mu-opioid receptor expression is associated with reduced disease-free and overall survival in laryngeal squamous cell carcinoma.

BACKGROUND: Expression of the mu-opioid receptor (MOR) is associated with poor long-term outcomes in various types of cancer. The association between MOR expression and clinical outcomes in laryngeal squamous cell carcinoma (LSCC) is not clear. METHODS: This retrospective study included patients who underwent laryngectomy for LSCC. The expression pattern of the MOR protein and OPRM1 gene in tumours and corresponding adjacent non-carcinoma specimens was measured. Propensity score matching was used to minimise bias. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were intraoperative sufentanil consumption, grade of surgical complications according to the Clavien-Dindo classification, and hospital length of stay. RESULTS: A total of 207 LSCC patients were enrolled. After propensity score matching, there was a significant difference in DFS between groups at 1, 3, and 5 yr (60.2% vs 81.2%, P=0.019; 39.4% vs 50.2%, P=0.026; 37.5% vs 42.5%, P=0.023, respectively) in patients with high MOR expression. The OS rates at 1, 3, and 5 yr were significantly lower in the high MOR expression group (81.2% vs 93.2%, P=0.027; 57.7% vs 78.3%, P<0.001; 42.5% vs 60.3%, P<0.001, respectively). The multivariate analysis indicated that high MOR expression was associated with worse DFS and OS (hazard ratio: 1.52, 95% confidence interval: 1.07, 2.25, P=0.034; hazard ratio: 1.42, 95% confidence interval: 1.17, 2.34, P=0.032). CONCLUSION: High MOR expression may be associated with poor prognosis in patients with LSCC, suggesting that MOR could be used as a valuable molecular biomarker to predict prognosis of LSCC patients.

Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study.

BACKGROUND: Intravenous lidocaine has been shown to reduce opioid consumption and is associated with favourable outcomes after surgery. In this study, we explored whether intraoperative lidocaine reduces intraoperative opioid use and length of stay (LOS) and improves long-term survival after pancreatic cancer surgery. METHODS: This retrospective study included 2239 patients who underwent pancreatectomy from January 2014 to December 2017. The patients were divided into non-lidocaine and lidocaine (bolus injection of 1.5 mg kg-1 at the induction of anaesthesia followed by a continuous infusion of 2 mg kg-1 h-1 intraoperatively) groups. The overall use of postoperative rescue analgesia and LOS were recorded. Propensity score matching was used to minimise bias, and disease-free survival and overall survival were compared between the two groups. RESULTS: After propensity score matching, patient characteristics were not significantly different between groups. Intraoperative sufentanil consumption and use of postoperative rescue analgesia in the lidocaine group were significantly lower than those in the non-lidocaine group. The LOS was similar between groups. There was no significant difference in disease-free survival between groups (hazard ratio [HR]=0.913; 95% confidence interval [CI], 0.821-1.612; P=0.316). The overall survival rates at 1 and 3 yr were significantly higher in the lidocaine group than in the non-lidocaine group (68.0% vs 62.6%, P<0.001; 34.1% vs 27.2%, P=0.011). The multivariable analysis indicated that intraoperative lidocaine infusion was associated with a prolonged overall survival (HR=0.616; 95% CI, 0.290-0.783; P=0.013). CONCLUSION: Intraoperative intravenous lidocaine infusion was associated with improved overall survival in patients undergoing pancreatectomy.

Effects of different carbon sources on 2,4,6-trichlorophenol degradation in the activated sludge process.

The effects of different carbon sources on the enrichment of 2,4,6TCP-degrading microbes and on reactor stability were was investigated using a lab-scale sequencing batch reactor (SBR). Glucose, sucrose, and starch were selected as different carbon sources because of the different molecular weights. The sucrose-fed activated sludge (AS) exhibited faster adaption and higher degradation rates for 2,4,6-TCP in long-term operation and typical cycles compared to that fed with glucose and starch. Large amounts of extracellular polymeric substance (EPS; 117.54 mg/gVSS) were induced from AS after adding starch, leading to a high SVI (191 mL/g) and poor sludge settling. This suggests that macromolecular carbon sources might have a detrimental effect on the reactor operation. Moreover, the high removal efficiency for TOC and chloride ions was achieved in a typical cycle of all SBRs, indicating that AS could completely mineralize 2,4,6-TCP. On average, more than 90% of the COD could be removed in all SBRs during long-term operation. Glucose, sucrose, and starch facilitated the development of a different microbial community compared to the seeding sludge, making Chloroflexi, Actinobacteria, and Proteobacteria the dominant phylum in the corresponding SBR. The microbial abundance associated with the metabolism of 2,4,6-TCP reached 81.02% due to the addition of sucrose. The results of this study could provide a potential guide for the effective selection of carbon sources in the treatment of chlorophenol wastewater.

[Visual analysis of coronavirus disease 2019 (COVID-19) studies based on bibliometrics].

To analyze the development of coronavirus disease 2019(COVID-19), this study systematically retrieved relevant Chinese and English literatures from both CNKI and Web of Science database platforms by bibliometric research method and CiteSpace 5.5.R2 software to obtain information and visualize relevant literatures. A total of 695 Chinese and 446 English literatures were included in this paper. Statistics showed that China had published most of the literatures and established close cooperation with the United States and the United Kingdom. Through the analysis, Tongji Medical College of Huazhong University of Science and Technology and its affiliated hospitals published the largest number of the publications. Moreover, the highly productive journals including Journal of Traditional Chinese Medicine and The Lancet covered eight major fields, such as medicine, medical virology, radiation medicine, infectious disease, and traditional Chinese medicine. Besides, a total of 35 special COVID-19 funds were recently established to subsidize these studies. The key words and themes analysis indicated that protein structure of COVID-19, receptor targets and mechanisms of action, integration of traditional Chinese and Western medicine, screening and development of antiviral drugs from traditional Chinese medicine and Western medicine, vaccine research as well as epidemiological characteristics and prediction are current study hotspots. This study provides a reference for researchers to rapidly master main study directions of COVID-19 and screen out relevant literatures.

Surgical trauma-induced CCL18 promotes recruitment of regulatory T cells and colon cancer progression.

BACKGROUND: Surgical stress has been suggested to facilitate colon cancer growth and metastasis. However, the precise mechanisms by which surgical trauma promotes colon cancer progression remain poorly understood. METHODS: To unravel the mechanisms underlying surgery-induced colon cancer progression, a syngenic transplantation tumor model was established with CT26 cells, and the effect of laparotomy on tumor progression was investigated. Especially, the expression of several chemokines was assessed, and their roles in recruiting CD4+ CD25+ regulatory T cells (Tregs) after surgery were analyzed. RESULTS: Tregs population was significantly increased in the tumor tissue and peripheral blood of tumor-bearing mice after laparotomy. C-C motif chemokine ligand 18 (CCL18) expression was significantly upregulated after laparotomy in tumor tissue and the peritoneal cavity of tumor-bearing mice, and it was positively correlated with the recruitment of Tregs. Functionally, CCL18 knockdown significantly reduces tumor growth and angiogenesis compared with control. Through analysis of Tregs, we found an upregulated proportion of Tregs in tumor tissue, peritoneal cavity, and peripheral blood after laparotomy, but this enhancement was blocked after CCL18 knockdown. In patients with colon cancer, a higher Tregs proportion is positively correlated to more advanced clinical TNM stages and shorter survival. Furthermore, a positive correlation was found between the serum CCL18 level and the Treg proportion in clinical samples. CONCLUSION: Surgical trauma contributes to colon cancer progression by increasing CCL18 expression and hence promotes Treg recruitment, which leads to an immunosuppressive environment.

Surgical trauma contributes to progression of colon cancer by downregulating CXCL4 and recruiting MDSCs.

Surgical stress has been shown to facilitate the tumor growth and metastasis of colon cancer. To unravel the mechanisms underlying surgery induced-colon cancer progression, a syngeneic transplantation tumor model was established with murine colon cancer CT26 cells and the effect of laparotomy on tumor progression was investigated. Especially the expression of several CXC chemokines was assayed, and its roles in regulating myeloid-derived suppressor cells (MDSCs) recruitment were analyzed. We found that laparotomy promoted in vivo tumor growth and angiogenesis. CXCL4 expression was significantly downregulated by laparotomy in the tumor tissue and the peritoneal cavity. Functionally, CXCL4 overexpression significantly reduces tumor volume compared to control. Through analysis of CD11b+/Gr1+ MDSCs cell, we found an upregulated proportion of MDSCs in the tumor tissues and peritoneal cavity following laparotomy, and this enhancement was blocked after CXCL4 overexpression. Further, a negative correlation was found between CXCL4 expression and MDSC amounts in clinical samples. Higher CXCL4 expression and lower MDSCs proportion is positively related to overall survival. CONCLUSION: Surgical trauma contributes to colon cancer progression by downregulating CXCL4 and hence promoting MDSC recruitment, which leads to an immunosuppressive environment.

Propofol attenuates TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells by inhibiting Ca2+/CAMK II/ERK/NF-κB signaling pathway.

Metalloproteinase 9 (MMP-9) is able to degrade collagen IV, an important component of blood-brain barrier (BBB). Expression of MMPs, especially MMP-9, correlates with BBB disruption during central nervous system inflammation. Propofol has been reported to have anti-inflammation effects. In this study, we investigated the effects of propofol on TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. The hCMEC/D3 cells were treated with propofol (25 µM), followed by TNF-α (25 ng/mL). We showed that TNF-α treatment markedly increased MMP-9 expression and decreased collagen IV expression in hCMEC/D3 cells, which was blocked by pretreatment with propofol. TNF-α-induced downregulation of collagen IV was also reversed by MMP-9 knockdown with siRNA. We revealed that TNF-α upregulated MMP-9 expression in hCMEC/D3 cells through activation of Ca2+/CAMK II/ERK/NF-κB signaling pathway; co-treatment with inhibitors of CaMK II (KN93), ERK (LY3214996), NF-κB (PDTC) or Ca2+chelator (BAPTA-AM) abrogated the effect of TNF-α on MMP-9 expression. We further established an in vitro BBB model by co-culturing of hCMEC/D3 cells and human astrocytes for 6 days and measuring trans-endothelial electrical resistance (TEER) to reflect the BBB permeability. TNF-α treatment markedly decreased TEER value, which was attenuated by pretreatment with propofol (25 µM) or MMP-9 knockdown with siRNA. In conclusion, propofol inhibits TNF-α-induced MMP-9 expression in hCMEC/D3 cells via repressing the Ca2+/CAMKII/ERK/NF-κB signaling pathway. TNF-α-impaired BBB integrity could be reversed by propofol, and propofol attenuates the inhibitory effect of TNF-α on collagen IV.

Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells.

Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to inhibit tumor metastasis in vitro. Human umbilical vein endothelial cells (HUVECs) cultured in Dulbecco's modified Eagle's medium were treated with tumor conditioned medium for 24 h, followed by 4 h of treatment with or without 25 µM of propofol, 10 µM of KN93, 500 µM of MK801, or 20 µM of rapastinel. It was found that propofol inhibited TEC adhesion and the glycolysis level of TECs. Consistently, propofol inhibited the expressions of adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and glycolysis proteins (GLUT1, HK2, and LDHA) in TECs. Moreover, propofol attenuated the expression of HIF-1α, the phosphorylation of AKT and Ca2+/calmodulin-dependent protein kinase II (CaMKII), and the Ca2+ concentration in TECs. MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMKII, both inhibited the expressions of adhesion molecules and glycolysis proteins, in a manner similar to propofol. Additionally, rapastine, an activator of NMDA receptor, could counteract the effects of propofol. Our results indicated that propofol attenuates intracellular Ca2+ concentration, CaMKII and AKT phosphorylation, and HIF-1α expression, probably via inhibiting the NMDA receptor, thus inhibiting glycolysis and adhesion of tumor and endothelial cells.

Acclimation of 2-chlorophenol-biodegrading activated sludge and microbial community analysis.

Using glucose as cosubstrate, activated sludge that could effectively biodegrade 40 mg/L 2-chlorophenol was successfully domesticated in sequencing batch reactors. To acclimate the sludge, 2-chlorophenol was increased stepwise from 0 to 40 mg/L. High-throughput sequencing revealed that the microbial community richness increased during the first 5 days of acclimation to 5 mg/L 2-chlorophenol and then decreased after another 20 days as 2-chlorophenol was increased. The original sludge obtained from a water resource recovery facility had the highest microbial diversity. As the acclimation continued further, community richness and diversity both increased, but they decreased again, significantly, when 2-chlorophenol reached 40 mg/L. Saccharibacteria_norank, Bacillus, Saprospiraceae_uncultured, and Lactococcus were the dominant bacteria. Bacillus and Pseudomonas were the main known chlorophenol-degrading bacteria. WCHB1-60_norank, Tetrasphaera, Comamonadaceae_unclassified, and Haliangium showed poor tolerance to 2-chlorophenol. Higher bacterial tolerance to chlorophenols does not mean higher degrading capability. The degradation of chlorophenols was not positively correlated with the detected abundance of known 2-chlorophenol-degrading bacteria. PRACTITIONER POINTS: Activated sludge that could effectively biodegrade 40 mg/L 2-chlorophenol was successfully domesticated using glucose as cosubstrate in sequencing batch reactors. Saccharibacteria_norank, Bacillus, Saprospiraceae_uncultured, and Lactococcus were the dominant bacteria. Bacillus and Pseudomonas were the main known chlorophenol-degrading bacteria detected in this study. The degrading capability and tolerance of bacteria to chlorophenols were relatively independent and the degradation of chlorophenols may be the synergistic effect of various bacteria.

Nalmefene attenuates malignant potential in colorectal cancer cell via inhibition of opioid receptor.

Morphine is postulated a risk factor in promoting tumor growth and metastasis during the preoperative period, and high glycolysis of tumor cells is proved to accelerate tumor progression. In this study, we investigated whether nalmefene, an opioid receptor inhibitor, could inhibit CT26 colon cancer cell growth through influencing cell glycolysis. CCK8 and transwell migration assays showed that nalmefene inhibited CT26 cells viability and migration in a concentration-dependent manner. Extracellular acidification rate and oxygen consumption rate showed that nalmefene inhibited glycolysis of CT26 cells. Moreover, western blot analysis and quantitative real-time PCR revealed that nalmefene decreased the expressions of enzymes related to glycolysis. Flow cytometry results revealed that intracellular calcium (Ca2+) level was changed by nalmefene, western blot analysis showed that nalmefene decreased calmodulin expression and calcium/calmodulin dependent protein kinases II (CaMK II) phosphorylation, thus inhibiting the serine/threonine kinase (AKT)-glycogen synthase kinase-3ß (GSK-3ß) pathway. Furthermore, the effects of KN93, an inhibitor of CaMK II, were similar to the effects of nalmefene, and the anti-tumor effect of nalmefene could be counteracted by morphine. In conclusion, the anti-tumor effect of nalmefene may be achieved by inhibiting opioid receptor and down-regulating calmodulin expression and CaMK II phosphorylation, thus inhibiting AKT-GSK-3ß pathway and the glycolysis of CT26 cells.