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Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major challenge for clinicians and patients with non-small cell lung cancer (NSCLC). Serine-arginine protein kinase 1 (SRPK1) is a key oncoprotein in the EGFR/AKT pathway that participates in tumorigenesis. We found that high SRPK1 expression was significantly associated with poor progression-free survival (PFS) in patients with advanced NSCLC undergoing gefitinib treatment. Both in vitro and in vivo assays suggested that SRPK1 reduced the ability of gefitinib to induce apoptosis in sensitive NSCLC cells independently of its kinase activity. Moreover, SRPK1 facilitated binding between LEF1, β-catenin and the EGFR promoter region to increase EGFR expression and promote the accumulation and phosphorylation of membrane EGFR. Furthermore, we verified that the SRPK1 spacer domain bound to GSK3β and enhanced its autophosphorylation at Ser9 to activate the Wnt pathway, thereby promoting the expression of Wnt target genes such as Bcl-X. The correlation between SRPK1 and EGFR expression was confirmed in patients. In brief, our research suggested that the SRPK1/GSK3β axis promotes gefitinib resistance by activating the Wnt pathway and may serve as a potential therapeutic target for overcoming gefitinib resistance in NSCLC.

Expression of Dual Specific Phosphatase-7 (DUSP7/PYST2) and it’s Connection with Salt Inducible Kinases (SIKs) and Downstream MKKs in breast cancer Wenxiao Ji1, Emily Ling Xin1,2, Lin Ye1, Eleri Davies3, Wen G. Jiang1, Tracey A. Martin1 1CCMRC, Cardiff University School of Medicine, Cardiff, Wales, UK 2Breast Centre, Peking University First Hospital, Xicheng District, Beijing, China 3Wales Breast Centre, University Llandough Hospital, Cardiff CF64 2XX, UK Introduction. DUSP7 is a member of the large Dual specific phosphatase family, able to regulate the phosphorylation of both tyrosine and serine/threonine protein kinases. The role of DUSP7 in cancer is not clear, however, it has been identified as a possible target for therapy in cancers including breast cancer. It has also been reported as having value in prognosis of certain cancers, such as haematological malignancies, breast cancer and certain types of gynaecological cancer. The signalling network for DUSP7 is not fully established but is known to connect to ERKs and MAP2Ks. DUSP7 also appears to be linked with salt inducible kinases (SIKs), a small family of kinases linked with progression and response to therapies in breast cancer. Thus, DUSP7 and salt inducible kinases may interact with each other and with the downstream kinases including MAP2Ks and STK11 to influence the clinical course of breast cancer. The present study explored if the pattern of DUSP7 together with salt inducible kinases and the downstream MKKs in breast cancer. Methods. The expression of DUSP7 was quantified in a cohort of breast cancer tissues (both normal mammary tissues and breast cancer tissues). The expression of the potential downstream kinases including MKK1, MKK2, MKK3, MKK4 and STK11 was also quantified. The expression profile of these molecule, together with the salt inducible kinases reported to be aberrant in our previous studies, were analysed against clinical and outcome information. Results. Breast cancer tissues expressed high levels of DUSP7 compared with normal mammary tissues, although not statistically significant. When we explored the relationship between DUSP7 and other potential related molecules in the database of the cohort, we found a highly significant correlation between DUSP7 and SIK1 (r=0.385, p< 0.001), SIK2 (r=0.590, p< 0.001), but not SIK3 (r=0.158, p>0.05). Together with SIK1 and SIK2 (known to link to drug sensitivity), DUSP7, MKK1 (MAP2K1) and MKK3 (MAP2K3) appear to form a gene signature that is of significant value in predicting the overall survival of the patients (ROC 0.723, p=0.001). This allowed us to significantly distinguish between those with good OS and poor OS (p< 0.001, Hazard Ration (HR) =1.443 (95%CI 1.154-1.804)). Multivariate analysis has shown that this signature is independent in predicting overall survival (p=0.013, HR=1.432). The signature is more significant in predicting OS in ER(-) tumours (p< 0.001) than ER(+) tumours (p=0.61). The same is seen when predicting OS with triple negative breast cancers (TNBC) (p< 0.001) than non-TNBC tumours (p=0.044). The gene signature also predicted disease free outcome (p=0.007, HR=1.266 (95% CI 1.065-1.504)). Conclusion. The dual specific phosphatase DUSP7 together with potentially correlated salt inducible kinases (SIK-1 and SIK-2) and downstream MKKs (MKK-1 and MKK3) have important clinical value in breast cancer. This provides support that DUSP7 may be a valuable therapeutic target in breast cancer. Citation Format: WENXIAO JI, Ling Xin, Eleri Davies, Wen G. Jiang, Lin Ye. Expression of Dual Specific Phosphatase-7 (DUSP7/PYST2) and it’s Connection with Salt Inducible Kinases (SIKs) and Downstream MKKs in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-22.

Objective. To evaluate whether traditional Chinese medicine compound preparations (TCMCPs) are associated with rheumatoid arthritis- (RA-) related complications (including readmission, Sjogren’s syndrome, surgical treatment, and all-cause death) in patients with RA. Methods. Clinical outcome data were retrospectively collected from patients with RA discharged from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2009 to June 2021. The propensity score matching method was used to match baseline data. Multivariate analysis was conducted to analyze sex, age, the incidence of hypertension, diabetes, and hyperlipidemia and identify the risk of readmission, Sjogren’s syndrome, surgical treatment, and all-cause death. Users of TCMCP and nonusers of TCMCP were defined as the TCMCP and non-TCMCP groups, respectively. Results. A total of 11,074 patients with RA were included in the study. The median follow-up time was 54.85 months. After propensity score matching, the baseline data of TCMCP users corresponded with those of non-TCMCP users, with 3517 cases in each group. Retrospective analysis revealed that TCMCP significantly reduced clinical, immune, and inflammatory indices in patients with RA, and these indices were highly correlated. Notably, the composite endpoint prognosis for treatment failure in TCMCP users was better than that in non-TCMCP users ( HR = 0.75 (0.71-0.80)). The risk of RA-related complications in TCMCP users with high-exposure intensity ( HR = 0.669 (0.650-0.751)) and medium-exposure intensity ( HR = 0.796 (0.691-0.918)) was significantly lower than those in non-TCMCP users. An increase in exposure intensity was associated with a concomitant decrease in the risk of RA-related complications. Conclusion. The use of TCMCPs, as well as long-term exposure to TCMCPs, may lower RA-related complications, including readmission, Sjogren’s syndrome, surgical treatment, and all-cause death, in patients with RA.

International audience; Abstract Whereas the technology spillover effect of international trade has been widely concerned by academic circles, the impact of trade barriers on technology spillover has received relatively less attention. This paper assesses the heterogeneity of international technology spillover effects in China’s manufacturing industry from traditional gross trade and value-added trade perspectives. Moreover, a deep insight into the effects of tariff and non-tariff barriers on international technology diffusion from traditional gross trade and value-added trade perspectives is also provided. Results show that the international trade indeed engenders technology diffusion, which is especially true in value-added trade characterized by intermediate goods trade compared with traditional gross trade. Additionally, tariff barriers severely disrupt technology diffusion in international trade, and traditional gross trade statistics underestimate the cumulative destructive effect of trade barriers on technology diffusion. Consequently, it can be concluded that reducing the abuse and misuse of non-tariff barriers can moderate the negative effect of trade barriers on international technology diffusion. JEL classification numbers: F14. Keywords: Global value chains; Value-added trade; Trade barriers; International technology spillover; Manufacturing industry.

Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China.A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression.A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%.Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.

Radix Salvia miltiorrhiza (RSM) is widely used for the clinical improvement of inflammatory diseases. However, the actions of RSM in the treatment of ankylosing spondylitis (AS) have not been fully explored. Therefore, this study was designed to use retrospective clinical data mining approach to understand the effects of RSM on AS-related immuno-inflammatory processes, use network pharmacology to predict therapeutic targets of RSM, and to further investigate the pharmacological molecular mechanism in vitro. RSM treatment has a long-term correlation with the improvement of AS-related immuno-inflammatory indicators through computational models. We established protein-protein interaction networks, conducted KEGG analysis to enrich significant TNF pathways, and finally obtained three core targets of RSM in the treatment of AS, namely, prostaglandin endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Screening of RSM active ingredients with node degree greater than 20 yielded cryptotanshinone and tanshinone IIA, and previous studies have reported their anti-inflammatory effects. In vitro, both cryptotanshinone and tanshinone IIA significantly inhibited the expressions of PTGS2, IL-6, and TNF-α in peripheral blood mononuclear cells in AS patients. In conclusion, cryptotanshinone and tanshinone IIA, which are the active components of RSM, may inhibit the activation of TNF signaling pathway in AS patients by downregulating the expression of PTGS2, IL-6, and TNF-α. These findings illustrate that RSM may be a promising therapeutic candidate for AS, but further validation is required.

Objectives: This study aimed to evaluate the effectiveness and safety of proprioceptive neuromuscular facilitation for chronic low back pain. Materials and methods: Eleven databases were searched from their inception through January 2021. The primary outcomes were pain intensity, individual activities, quality of life, and adverse events. Results: Four randomized controlled trials (RCTs) with 184 patients (mean age: 37.8±3.1 years; range, 35 to 50 years) met the inclusion criteria. The pooled effect size showed proprioceptive neuromuscular facilitation, relieved pain (standard means difference [SMD]: -0.835, 95% CI: -1.139 to -0.531, p Conclusion: This study verified that proprioceptive neuromuscular facilitation could relieve pain and improve individual activities without serious adverse events in patients with CLBP; however, it should be cautiously recommended due to the small number of included RCTs.

Objective. This study aimed to analyze the effect of traditional Chinese medicine (TCM) on the risk of readmission for rheumatoid arthritis (RA) patients with anemia. Methods. In this study, 893 hospitalized RA patients were followed up by telephone. A retrospective cohort study was conducted using propensity score matching (PSM). The Cox proportional hazards model was used to assess the influence of various factors on the risk of readmission for RA patients with anemia. The Kaplan–Meier survival curve was utilized to analyze the effect of TCM intervention time on readmission. Results. The incidence of anemia was 58.08% (471/811) in RA patients. After 1 : 1 PSM, 328 RA patients with anemia and 328 RA patients without anemia were finally included in our study. The readmission rate of anemia patients was higher than that of patients without anemia ( P < 0.01 ). The readmission rate of RA patients with anemia was obviously lower in the TCM group than in the non-TCM group ( P < 0.01 ). The Cox proportional hazards model showed TCM as an independent protective factor as it decreased the risk of readmission by 50% (HR = 0.50, 95% CI = 0.27–0.94, P = 0.03 ) in RA patients with anemia. In addition, the risk of readmission was dramatically diminished in the high-exposure subgroup (TCM > 12 months) compared with the low-exposure subgroup (TCM ≤ 12 months) (log-rank P = 0.016 ). Conclusion. TCM, as a protective factor, is associated with a reduced risk of readmission in RA patients with anemia.

Objective. The goal of this research was to probe the mechanism of Huangqin Qingre Chubi(HQC) in the improvement of immune inflammation of Ankylosing spondylitis(AS). Methods. Clinical data mining was implemented to assess the efficacy of HQC in AS therapy. The target network of HQC active ingredients for AS therapy was established by network pharmacology. The relationships between HQC active ingredients and major objectives of AS were forecasted by molecular docking technology. Finally, Cytological tests were performed for the evaluation of the effects of the drugs on the core targets. Results. Clinical data mining indicated that HQC was highly related to the improvement of immunoinflammatory markers.Network pharmacology results demonstrated that the main targets of HQC, including Peroxisome proliferator-activated receptor gamma (PPARG),Prostaglandin G synthase 2(PTGS2), recombinant catalase(CAT), Chemokine (C-X-C motif) ligand 8(CXCL8), and Vascular endothelial growth factor(VEGFA), were closely associated with the signaling pathways of IL-17, NF-kappa B, TNF, T cell receptor, and Th1, and Th2 cell differentiation in AS therapy. In the molecular docking analysis of the HQC active components, 70% of the binding energy was under -4.25 kcal/mol, and 53% of the binding energy was no more than -5.0 kcal/mol, of which the binding energy of stigmasterol with PPARG, CXCL8, and CAT were under -7.50 kcal/mol, implying that the chemically active ingredients of HQC formula have good binding activity against inflammatory targets. In vitro cell experiment results suggested that HQC down-regulated the expression of PTGS2, and up-regulated the expression of PPARG and CAT. Conclusion. HQC exerts functions in improving the immune inflammatory indicators in patients with AS for the reason that the active ingredient of Traditional Chinese medicine(TCM) in HQC act through oxygen species, oxidative stress, transcription factors, and apoptosis.

Background Pecto-intercostal fascial block (PIFB) provides analgesia for cardiac median sternotomy, but many patients complain of severe drainage pain that cannot be covered by PIFB. Rectus sheath block (RSB) has been attempted to solve this problem, but whether PIFB combined with RSB can achieve better analgesia is uncertain. Methods This was a single-center randomized controlled trial at Peking University People’s Hospital from September 22, 2022 to December 21, 2022. Patients undergoing elective cardiac surgery with a median sternotomy were randomized at a 1:1 ratio to receive either bilateral PIFB and RSB (PIFB + RSB group) or PIFB (PIFB group). The primary outcome was intravenous opioid consumption within 24 h after surgery. Secondary outcomes included opioid consumption within 48 h, postoperative pain scores, time to extubation, and length of stay in the hospital. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α before and the first 24 h after surgery were measured. Results A total of 54 patients were analyzed (27 in each group). Intravenous opioid consumption within 24 h after surgery was 2.33 ± 1.77 mg in the PIFB + RSB group vs 3.81 ± 2.24 mg in the PIFB group (p = 0.010). Opioid consumption within 48 h after surgery was also reduced in the PIFB + RSB group (4.71 ± 2.71 mg vs 7.25 ± 3.76 mg, p = 0.006). There was no significant difference in pain scores, time to extubation, length of stay in hospital, or the levels of IL-6, IL-10 and TNF-α between the two groups. Conclusions The combination of PIFB and RSB reduced postoperative intravenous opioid consumption until 48 h after cardiac surgery. Trial registration This trial is registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR2200062017) on 19/07/2022.

ObjectivesEpidural and paravertebral block reduce the extubation time in patients undergoing surgery under general anesthesia but are relatively contraindicated in heparinized patients due to the potential risk of hematoma. The Pecto-intercostal fascial block (PIFB) is an alternative in such patients.MethodsThis is a single-center randomized controlled trial. Patients scheduled for elective open cardiac surgery were randomized at a 1:1 ratio to receive PIFB (30 ml 0.3% ropivacaine plus 2.5 mg dexamethasone on each side) or saline (30 ml normal saline on each side) after induction of general anesthesia. The primary outcome was extubation time after surgery. Secondary outcomes included opioid consumption during surgery, postoperative pain scores, adverse events related to opioids, and length of stay in the hospital.ResultsA total of 50 patients (mean age: 61.8 years; 34 men) were randomized (25 in each group). The surgeries included sole coronary artery bypass grafting in 38 patients, sole valve surgery in three patients, and both procedures in the remaining nine patients. Cardiopulmonary bypass was used in 20 (40%) patients. The time to extubation was 9.4 ± 4.1 h in the PIFB group vs. 12.1 ± 4.6 h in the control group (p = 0.031). Opioid (sufentanil) consumption during surgery was 153.2 ± 48.3 and 199.4 ± 51.7 μg, respectively (p = 0.002). In comparison to the control group, the PIFB group had a lower pain score while coughing (1.45 ± 1.43 vs. 3.00 ± 1.71, p = 0.021) and a similar pain score at rest at 12 h after surgery. The two groups did not differ in the rate of adverse events.ConclusionsPIFB decreased the time to extubation in patients undergoing cardiac surgery.Trial RegistrationThis trial is registered at the Chinese Clinical Trial Registry (ChiCTR2100052743) on November 4, 2021.

Backgrounds To preliminary evaluate the application of novel SaCoVLM video laryngeal mask -guided intubation for anesthetized children. Methods One hundred twenty-four children with microtia (ages 5-15 years,) who required general intubation anaesthesia, were enrolled in the study. After induction of general anesthesia,guided tracheal intubation under direct vision of the SaCoVLM was performed. Our primary outcome was first-pass success rate of guided tracheal tube placement. Secondary outcome included glottic visualization grades, the first-attempt success rate of LMA placement, the time for LMA placement and time to endotracheal intubation as well as the time for LMA removal after successful intubation, the fiberoptic grade of laryngeal view, the baseline and postinduction hemodynamic parameters were also recorded,and the incidence 24 h complications after operation. Results The first-pass success rate of guided tracheal tube placement was 91.1% (95%CI = 1.04–1.14), the status of glottic visualization was classified: grade 1 in 27cases, grade 2 in 36 cases, grade 3 in 41 cases and grade 4 in 20 cases. The first success rate of LMA placement was 92.7% (95%CI = 1.03–1.13), the time for LMA insertion was 15.7 (±9.1) s, intubation time was 30.9 (±17.6) s and withdrawl time was 24.9 (±9.3) s. The incidence of postoperative sore throat at 2 h was 29%, and 16.1% at 24 h, without dysphagia and hypoxia. Conclusion The SaCoVLM video laryngeal mask-guided intubation is feasible in children, with a high success rate, could be a new promising device to guide intubation in airway management. Trial registration This study was approved by the University’s Institutional Review Board and written informed consent was obtained from all subjects participating in the trial. The trial was registered prior to patient enrollment at clinicaltrials.gov (ChiCTR2200061481, http://www.chictr.org.cn. Principal investigator: Juan Zhi; Date of registration: 26/06/2022.

International audience; The Jiangmen Underground Neutrino Observatory (JUNO), the first multi-kton liquid scintillator detector, which is under construction in China, will have a unique potential to perform a real-time measurement of solar neutrinos well below the few MeV threshold typical for Water Cherenkov detectors. JUNO's large target mass and excellent energy resolution are prerequisites for reaching unprecedented levels of precision. In this paper, we provide estimation of the JUNO sensitivity to 7Be, pep, and CNO solar neutrinos that can be obtained via a spectral analysis above the 0.45 MeV threshold. This study is performed assuming different scenarios of the liquid scintillator radiopurity, ranging from the most opti mistic one corresponding to the radiopurity levels obtained by the Borexino experiment, up to the minimum requirements needed to perform the neutrino mass ordering determination with reactor antineutrinos - the main goal of JUNO. Our study shows that in most scenarios, JUNO will be able to improve the current best measurements on 7Be, pep, and CNO solar neutrino fluxes. We also perform a study on the JUNO capability to detect periodical time variations in the solar neutrino flux, such as the day-night modulation induced by neutrino flavor regeneration in Earth, and the modulations induced by temperature changes driven by helioseismic waves.

A POMOF with [W10O32]4− and mononuclear cobalt clusters as connecting nodes, which can be used as a photocatalyst to reduce low concentrations of CO2 in flue gas to generate syngas.

Objective. This study aimed to ascertain the immuno-inflammatory molecular targets of Xinfeng capsules (XFC) in the treatment of ankylosing spondylitis (AS) based on data mining, network pharmacology, and molecular docking. Methods. The efficacy of XFC in the treatment of AS was assessed by clinical data mining. Network pharmacology was utilized to establish a network of the targets for XFC active ingredients in the treatment of AS. The binding mode and affinity of XFC active ingredients to the key targets for AS were predicted using molecular docking. Results. XFC significantly diminished immuno-inflammatory indicators of AS. In total, 208 targets of XFC were obtained from the TCMSP database and 629 disease targets of AS were screened from the GeneCards database, which were intersected to yield 57 targets of XFC in the treatment of AS. Protein-protein interaction, gene ontology, and Kyoto genome encyclopedia analyses showed that XFC might activate TNF and NF-κB signaling pathways. Quercetin, kaempferol, triptolide, and formononetin had free binding energies

The bacterial flagellar motor is a rotary machine composed of functional modular components, which can perform bidirectional rotations to control the migration behavior of the bacterial cell. It resembles a two-cogwheel gear system, which consists of small and large cogwheels with cogs at the edges to regulate rotations. Such gearset models provide elegant blueprints to design and build artificial nanomachinery with desired functionalities. In this work, we demonstrate DNA assembly of a structurally well-defined nanodevice, which can carry out programmable rotations powered by DNA fuels. Our rotary nanodevice consists of three modular components, small origami ring, large origami ring, and gold nanoparticles (AuNPs). They mimic the sun gear, ring gear, and planet gears in a planetary gearset accordingly. These modular components are self-assembled in a compact manner, such that they can work cooperatively to impart bidirectional rotations. The rotary dynamics is optically recorded using fluorescence spectroscopy in real time, given the sensitive distance-dependent interactions between the tethered fluorophores and AuNPs on the rings. The experimental results are well supported by the theoretical calculations.

Ankylosing spondylitis (AS) has a high disability rate, and an early diagnosis is difficult.To explore the possible functions and underlying mechanism of circular RNAs Homo sapiens (hsa)_circ_0003307 in ankylosing spondylitis.The hsa_circ_0003307 expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of 30 AS patients and 30 healthy controls (HC) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues, established as cell lines and cultured for subsequent cell experiments involving transfection with different vectors. The qRT-PCR analysis was used for evaluating the levels of hsa_circ_0003307 in AS-FLS. Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein levels were measured using western blotting and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. Spearman's correlation analysis was used to assess the correlation between hsa_circ_0003307 and clinical characteristics.The expression level of hsa_circ_0003307 was significantly high in AS patients and was positively associated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). We found that hsa_circ_0003307 overexpression could promote the activation of the PI3K/AKT pathway and expression of inflammatory cytokines - tumor necrosis factor alpha (TNF-α) and TNF-α-induced protein 2 (TNFAIP2). However, hsa_circ_0003307 knockdown reduced the expression of TNF-α and TNFAIP2.The expression level of hsa_circ_0003307 was associated with inflammatory response, and it was revealed that hsa_circ_0003307 knockdown could reduce the inflammatory response of AS by regulating the PI3K/AKT pathway.

The high incidence of chronic postsurgical pain (CPSP) has been a major issue after breast cancer surgery (BCS). The impact of regional anesthesia (RA) techniques on CPSP remains conflicting. In this propensity score-matched cohort study, we aimed to investigate the effect of preoperative single-shot erector spinae plane block (ESPB) adding to general anesthesia (GA) on the incidence of CPSP at 1 year following BCS. Data of adult female patients who underwent unilateral BCS between October 2019 and June 2020 were retrospectively collected. Patients were grouped to ESPB combined with GA (ESPB + GA) and GA alone, respectively. All patients were prospectively followed up at 1 year after surgery. CPSP and neuropathic pain (NP) were measured using the brief pain inventory–short form (BPI-SF) and ID Pain scale. Eleven confounding factors were managed by propensity score matching (PSM) to achieve between-group balance. The primary outcome was the incidence of CPSP at 1 year after BCS. The secondary outcomes include proportion of NP, severity, and interference of CPSP at 1 year after surgery, acute postoperative pain, postoperative nausea and vomiting (PONV), hospital length of stay (LOS), and adverse events. After PSM, data for 194 patients were available for analysis (97 in each group). No significant difference in the incidence of CPSP (P = 1.000) nor percentage of patients with NP (P = 0.442) was found between the two groups. Both matched groups had similar intensity of CPSP (P = 0.547) measured by BPI-SF as well as the rates of moderate to severe CPSP (P = 1.000). A significant decrease in acute pain scores (P = 0.043) and rates of rescue analgesics demand (P = 0.042) were observed in the ESPB + GA group compared to the GA group. Multivariate logistic regression on the total study cohort showed that axillary lymph node dissection (ALND) (OR 3.541, 95% CI: 1.273–9.851, P = 0.015), radiotherapy (OR 1.918, 95% CI: 1.067–3.448, P = 0.029) and acute postoperative pain within 24 h (OR 2.109, 95% CI: 1.097–4.056, P = 0.036) were independent risk factors for the development of CPSP. We found that preoperative single-shot ESPB was not associated with reduced incidence of CPSP at 1 year after BCS. ALND, radiotherapy, and acute postoperative pain within 24 h were independent risk factors for the development of CPSP after BCS. The study was registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000038464, date of registration: September 23, 2020).

BACKGROUND Several groups have previously developed logistic regression models for predicting delayed graft function (DGF). In this study, we used an automated machine learning (ML) modeling pipeline to generate and optimize DGF prediction models en masse. METHODS Deceased donor renal transplants at our institution from 2010 to 2018 were included. Input data consisted of 21 donor features from United Network for Organ Sharing. A training set composed of ~50%/50% split in DGF-positive and DGF-negative cases was used to generate 400 869 models. Each model was based on 1 of 7 ML algorithms (gradient boosting machine, k-nearest neighbor, logistic regression, neural network, naive Bayes, random forest, support vector machine) with various combinations of feature sets and hyperparameter values. Performance of each model was based on a separate secondary test dataset and assessed by common statistical metrics. RESULTS The best performing models were based on neural network algorithms, with the highest area under the receiver operating characteristic curve of 0.7595. This model used 10 out of the original 21 donor features, including age, height, weight, ethnicity, serum creatinine, blood urea nitrogen, hypertension history, donation after cardiac death status, cause of death, and cold ischemia time. With the same donor data, the highest area under the receiver operating characteristic curve for logistic regression models was 0.7484, using all donor features. CONCLUSIONS Our automated en masse ML modeling approach was able to rapidly generate ML models for DGF prediction. The performance of the ML models was comparable with classic logistic regression models.

Background This study aims to describe the association between sharp score and clinical indexes, bone metabolism indexes, Disease Activity Score (DAS28) and sociodemographic factors in rheumatoid arthritis (RA). Methods Data were collected from the HIS (hospital information system), a national inpatient database in China, with information on the patients hospitalized during the period from 2012 to 2019. The association between sharp score and effective factors were identified using multinomial logistic regression and association rule mining (ARM). Results Three thousand eight hundred and forty patients were included: 82.66% males, 17.34% females, mean (SD) age 56.95 (12.68) years and symptom duration 3.45 (1.09) years. Spearman correlation analysis and Association rules analysis showed that there were significant positive correlations between sharp score and effective factors. Logistic regression analysis presented that erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (CRP), rheumatoid factor (RF) were risk factors of sharp score. In the analysis of individual outcomes, sex, age, symptom duration, DSA28 score, RF, ever drinker, and radiographic grading of hands were influence factors of sharp score. Conclusion Sharp score should be taken into consideration in formulating treatment strategies in RA.

Soil moisture is a limiting factor for vegetation restoration on the Loess Plateau, China. Micro-topography may cause heterogeneities in the distribution of soil moisture, but little is known about its effect on deep soil moisture. Our study aims to explore the distribution and impact of soil moisture within the upper 10 m of soil for different microtopographies. Taking undisturbed slope as the control, five micro-topographies were selected. Soil moisture over a depth of 0–10 m from 2017 to 2019 was investigated, and soil particle size and soil organic matter were measured. Variance analysis and multiple comparisons were used to analyze the difference in soil moisture for different microtopographies and multiple-linear regression was used to analyze the influence of micro-topography on soil moisture. There are significant differences in soil moisture within the different layers underlying the examined micro-topographies, while the inter-annual variation in soil water storage for the selected microtopographies increase with increased rainfall. The depth of influence of micro-topographic vegetation on soil moisture exceeded 1000 cm for a gully (GU), 740 cm for a sink hole (SH), 480 cm for a scarp (SC), 360 cm for an ephemeral gully (EG) and 220 cm for a platform (PL). Micro-topography will cause the heterogeneous distribution of soil moisture in the shallower layers, which changes the vegetation distribution differences between micro-topographies. This may be the survival strategy of herbaceous vegetation in response to climate change in the Loess Plateau. For future vegetation restoration efforts, we need to pay attention to the influence of microtopography on soil moisture.

Rationale & objectiveRecent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study.Study designCross-sectional study.Setting & participants637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020.ExposureCreatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable.OutcomesEquation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80mL/min/1.73m2.Analytical approachGFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance.ResultsThe median bias of the CKDEPI21 equation underestimated mGFR by 2.8mL/min/1.73m2. The bias in the Black subgroup underestimated mGFR by 9.0mL/min/1.73m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80mL/min/1.73m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80mL/min/1.73m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment).LimitationsLimited sample of individuals identifying as Black. Lack of cystatin C data.ConclusionsIn our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

Background Air pollution has been identified as related to the diseases of susceptible population, but the spatial heterogeneity of its economic burden and its determinants are rarely investigated. The issue is of great policy significance, especially after the epidemic of COVID-19, when human are facing the joint crisis of health and environment, and some areas is prone to falling into poverty. Methods The geographical detector was adopted to study the spatial distribution characteristics of the incidence of catastrophic health expenditure (ICHE) for older adults in 100 rural areas in China at the prefecture-city level. The health factors, sociological factors, policy factors and environmental factors and their interactions are identified. Results First, most health service factors had strong explanatory power for ICHE whether it interacts with air pollution. Second, 50 single-factor high-risk areas of ICHE were found in the study, but at the same time, there were 21 areas dominated by multiple factors. Conclusion The different contributions and synergy among the factors constitute the complex mechanism of factors and catastrophic health expenditure. Moreover, during this process, air pollution aggravates the contribution of health service factors toward ICHE. In addition, the leading factors of ICHE are different among regions. At the end, this paper also puts forward some policy suggestions from the perspective of health and environment crisis in the post-COVID-19 world: environmental protection policies should be combined with the prevention of infectious diseases; advanced health investment is the most cost-effective policy for the inverse health sequences of air pollution and infectious diseases such as coronavirus disease 2019 (COVID-19); integrating environmental protection policy into healthy development policy, different regions take targeted measures to cope with the intertwined crisis.

Patients with primary Sjögren's syndrome (pSS) reportedly believe that their symptoms worsen on extreme weather days due to variations in environmental conditions. However, few studies have assessed the acute effects of environmental exposure on the onset of pSS. This study aimed to evaluate the exposure-response relationship between extreme environmental conditions and pSS outpatient visits.We obtained data on pSS outpatient visits from two provincial general hospitals in Hefei, China, during 2014-2019. A distributed lag non-linear model was used to estimate the exposure-lag-response relationship between environmental variables and pSS.We detected significant and non-linear associations between extreme environments and pSS. The estimated relative risk (RR) for a lag of 3 days was 1.11 (95% CI: 1.03 to 1.19) for extreme cold and for a lag of 21 days was 1.07 (95% CI: 1.01 to 1.12) for extreme dampness. Long sunshine duration was positively correlated with pSS (lag 11, 1.05, 95% CI: 1.01 to 1.08). Moreover, female patients were more susceptible to these effects. Patients older than 65 years old were more vulnerable to frigid environments (lag 3, RR = 1.30, 95% CI: 1.09 to 1.54), while younger patients were more vulnerable to extreme dampness (lag 21, RR = 1.10, 95% CI: 1.03 to 1.16). Extreme cold and high humidity were negatively correlated with the same-day outpatient visits.Our findings suggest a potential relationship between exposure to extreme environmental conditions and increased risk of pSS outpatient visits. We therefore suggest that policymakers and doctors aim to further our understanding of environmental effects on pSS and adopt adequate measures to alleviate pSS symptoms. Key Points • Extreme cold, extreme dampness, and long sunshine duration increased the risk of pSS outpatient visits, especially for females. • Young pSS patients are more susceptible to a rise in humidity. • Elderly pSS patients are more sensitive to extreme cold weather.

Dexmedetomidine had sedative and analgesic effects and did not produce significant respiratory depression at therapeutic doses. To compare the sedative and analgesic effects and safety of dexmedetomidine combined with remifentanil or sufentanil in patients undergoing liposuction. A total of 100 subjects were randomized 1:1 to two groups: Group R and Group S. First, patients were administered midazolam 0.02 mg·kg−1. Anesthesia was induced with an intravenous infusion of dexmedetomidine 1 µg kg−1 (15 min) and remifentanil 0.1 µg kg−1 min−1 (Group R) or sufentanil 0.1 µg kg−1h−1 (Group S). Anesthesia was maintained with an intravenous infusion of dexmedetomidine 1.0 µg kg−1h−1, midazolam 0.015 mg kg−1h−1, remifentanil 0.1 µg kg−1min−1 (Group R), or sufentanil 0.1 µg kg−1h−1 (Group S). Hemodynamic and respiratory changes, modified OAA/S score and BIS values, postoperative Visual Analogue Scale pain scores, satisfaction of the patient and surgical team with the procedure, and adverse events and recovery time were recorded. Group R received significantly less midazolam and midazolam per hour compared to Group S (Group R vs. Group S: 3.4 ± 1.7 mg vs. 5.1 ± 2.0 mg, P

The Chinese species of Larnaca are reviewed. A new species, Larnaca (Larnaca) walle sp. nov. is described from China. Female of Larnaca (Larnaca) emarginata Bian, Guo & Shi, 2015 is described for the first time. The type specimen is deposited in Museum of Biology, East China Normal University.

Esophageal cancer is a malignant tumor with a five-year survival rate of less than 20%. Early diagnosis and exploration of esophageal cancer pathogenesis are of great significance for the treatment and prognosis of esophageal cancer. Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of different types of tumors. However, the role of exosome LncRNA in esophageal squamous cell carcinoma (ESCC) is rarely reported. In this study, we detected high expression of lncRNA LINC01711 in ESCC tissues and was associated with poor prognosis. Silencing LINC01711 can inhibit the proliferation, migration, invasion, and growth of ESCC cell lines, and induce apoptosis. Linc01711 was identified as a competitive endogenous RNA that suppressed miR-326, and up-regulated the expression of fascin actin-bundling protein 1 (FSCN1). Besides, in vivo experiments showed that the administration of exosome-derived LINC01711 (LINC01711-Exo) promoted the growth of tumors in nude mice. In general, exosomal LINC01711 promoted the proliferation, migration, and invasion of esophageal cancer cells by up-regulating FSCN1 and down-regulating miR-326, thus improved the occurrence and development of ESCC.

Background Patients with ankylosing spondylitis (AS) have reported that their pain becomes worse when the local weather changes. However, there is limited evidence verifying the short-term associations between meteorological factors and outpatient visits for patients with AS. Therefore, this study evaluates this possible association. Methods Meteorological data and data on daily AS outpatient visits to a general hospital in Hefei, China, from 2014 to 2019 were collected and analysed. Distributed lag nonlinear models and Poisson regression models were employed to determine the association between weather conditions and outpatient visits; the results were also stratified by gender and age. Results High relative humidity is significantly associated with all patient visits in lag 1 (RR = 1.113, 95% CI 1.021 to 1.213) and lag 7 days (RR = 1.115, 95% CI 1.014 to 1.227). A low relative risk to the nadir is observed in lag 4 days (RR = 0.920, 95% CI 0.862 to 0.983). Male and young patients ( Conclusions Our findings suggest a potential relationship between exposure to weather conditions and increased risk of AS outpatient visits. These results can aid hospitals in preparing for and managing hospital visits by AS patients when the local weather conditions change.

Yaobitong capsule is a compound preparation of traditional Chinese medicine that has been widely applied in disease treatment. To insight into the therapeutic effects of the yaobitong capsule on rheumatoid arthritis and its mechanisms, a liquid chromatography-mass spectrometry untargeted urine metabolomics method was established and validated, combined with the quantitative analysis of seven potential amino acid biomarkers in rat urine. The results showed that 35 potential biomarkers were found in untargeted metabonomics, which was related to amino acid metabolism, lipid metabolism, energy metabolism, and purine metabolism. Moreover, seven amino acid biomarkers, including proline, methionine, glutamic acid, histidine, lysine, cysteine, and glutamine, were further separated and quantified in multiple-reaction monitoring with a positive ionization mode. Then the linearity, standard curves, accuracy, precision, limit of quantitation, recovery, stability, carryover, and matrix effect of the quantitative method were examined. Finally, the validated method was successfully applied to investigate the urine samples of the control group, adjuvant-induced rheumatoid arthritis model group, yaobitong capsule-treatment group, and positive control group in rats. The contents of seven amino acids in different groups showed significant differences. Consequently, our findings revealed that the yaobitong capsule exerted therapeutic effects on rheumatoid arthritis rats by maintaining amino acid homeostasis.

The intertidal zone, due to its location in the transition zone of terrestrial and marine ecosystems, is seriously disturbed by anthropogenic activities such as fuel combustion and industrial production, causing significant increase in dissolved organic matter (DOM). However, the distribution and properties of DOM in intertidal sediments at the large scale and their correlations with local socio-economic indicators remain unclear. In this study, we collected sediment samples from 13 intertidal zones across 11 coastal provinces in China and analyzed optical properties and compositions of sedimentary DOM. The results showed that the physico-chemical properties of sediment, such as pH and texture, affected the content of organic matter, thereby influencing the concentration of sedimentary DOM indirectly. The contents of fulvic acid- and protein-like components were relatively higher than humic acid-like component at all sampling sites. Moreover, urbanization could lead to the release of aromatic and humified organic matters into intertidal zones. Unlike coal, oil consumption exhibited positive correlation with SUVA

Background As the fifth-largest global mortality risk factor, air pollution has caused nearly one-tenth of the world’s deaths, with a death toll of 5 million. 21% of China’s disease burden was related to environmental pollution, which is 8% higher than the US. Air pollution will increase the demand and utilisation of Chinese residents’ health services, thereby placing a greater economic burden on the government. This study reveals the spatial impact of socioeconomic, health, policy and population factors combined with environmental factors on government health expenditure. Methods Spearman’s correlation coefficient and GeoDetector were used to identify the determinants of government health expenditure. The GeoDetector consist of four detectors: factor detection, interaction detection, risk detection, and ecological detection. One hundred sixty-nine prefecture-level cities in China are studied. The data sources are the 2017 data from China’s Economic and Social Big Data Research Platform and WorldPOP gridded population datasets. Results It is found that industrial sulfur dioxide attributed to government health expenditure, whose q value (explanatory power of X to Y) is 0.5283. The interaction between air pollution factors and other factors will increase the impact on government health expenditure, the interaction value (explanatory power of × 1∩× 2 to Y) of GDP and industrial sulfur dioxide the largest, whose values is 0.9593. There are 96 simple high-risk areas in these 169 areas, but there are still high-risk areas affected by multiple factors. Conclusion First, multiple factors influence the spatial heterogeneity of government health expenditure. Second, health and socio-economic factors are still the dominant factors leading to increased government health expenditure. Third, air pollution does have an important impact on government health expenditure. As a catalytic factor, combining with other factors, it will strengthen their impact on government health expenditure. Finally, an integrated approach should be adopted to synergisticly governance the high-risk areas with multi-risk factors.

Enterococci are one of the main causes of gastrointestinal tract infections in the healthcare system and can develop resistance to fosfomycin through plasmid or chromosomally encoded fosfomycin resistance genes. To investigate the mechanisms of fosfomycin resistance, a total of 4,414 clinical isolates of non-replicated clinical enterococci collected from 62 hospitals in 26 provinces or cities in China were tested. Antibiotic susceptibility testing, detection of fosfomycin resistance genes, and cloning of the fosX gene were done. The PFGE, MLST, qRT-PCR, and next genome sequencing were carried out. The results revealed that the fosfomycin-resistant rate of enterococci was 3.5% (153/4,414), and the major resistance mechanism was fosX (101/153) and fosB (52/153) genes. The fosX gene could increase 4- fold fosfomycin MIC in Enterococcus faecium BM4105RF transformants, and the results of PFGE showed the 101 E. faecium carrying fosX were grouped into 48 pulse types. The multilocus sequence typing identified ST555 as the vast majority of STs, mostly distributed in Shanghai, China. Furthermore, the fosX gene expression was strongly related to the fosfomycin-resistant levels of enterococci. The present study was the first to describe the high prevalence presence of the fosX gene in E. faecium from China.