Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective:To investigate the mechanism of long non-coding RNA taurine up-regulated gene 1(lncRNA TUG1)in acute pancreatitis(AP).Methods:The mouse pancreatic acinar cell line(MPC-83)was cultured in vitro,and treated with lipopoly-saccharide(LPS,10 μg/ml)and cerulein(Caerulein,100 nmol/L)for 3 h to establish the AP model.The experiment was divided into control group,AP group,AP+sh-NC group,AP+sh-TUG1 group,AP+sh-TUG1+inhibitor-NC group,and AP+sh-TUG1+miR-31-5p inhibitor group.Quantitative real-time PCR(qRT-PCR)was performed to measure the expression levels of lncRNA TUG1 and miR-31-5p in cells;CCK-8 method was performed to measure cell viability;flow cytometry was performed to measure apoptosis;ELISA was performed to measure the levels of IL-1β and tumor necrosis factor α(TNF-α)in the cell supernatant;and dual-luciferase reporter gene experiments was performed to verify the targeting relationship between lncRNA TUG1 and miR-31-5p.The AP mouse model was constructed,and after corresponding intervention,qRT-PCR was performed to determine the lncRNA TUG1 and miR-31-5p expres-sion levels in pancreatic tissue;the serum inflammatory factors IL-1β,TNF-α contents and amylase(AMY)and lipase(Lipase)activities were determined by kits;HE staining was performed to observe histopathological changes of pancreas;TUNEL was per-formed to detect apoptosis in pancreatic tissue.Results:In MPC-83 cells co-treated with Caerulein and LPS,the lncRNA TUG1 level,apoptosis rate,IL-1β and TNF-α levels were increased,while miR-31-5p level and cell viability were decreased(all P<0.05);knock-down of lncRNA TUG1 up-regulated miR-31-5p,increased cell viability,decreased IL-1β and TNF-α levels,and inhibited cell apop-tosis(all P<0.05);down-regulation of miR-31-5p expression attenuated the inhibitory effect of lncRNA TUG1 knockdown on cellular inflammatory responses.miR-31-5p was a direct target of lncRNA TUG1.Knockdown of lncRNA TUG1 expression in vivo was able to up-regulate the expression of miR-31-5p in pancreatic tissue of AP mice,reduce the levels of IL-1β and TNF-α,reduce cell apoptosis,and improve pancreatic tissue damage.Conclusion:Knockdown of lncRNA TUG1 may improve AP by up-regulating the expression level of miR-31-5p and inhibiting the inflammatory response.

Objective To investigate the relationships of the subsets and activation factors of peripheral blood innate lymphocytes (ILCs) with postoperative intracranial infection in patients with hypertensive basal ganglia hemorrhage. Methods A total of 105 patients with postoperative intracranial infection (infection group) and 105 patients without infection (non-infection group) were selected as research subjects. The patients in the infection group were divided into mild infection group (n=33), moderate infection group (n=50) and severe infection group (n=22) according to the severity of postoperative intracranial infection. The patients in the infection group were divided into good prognosis group (n=53) and poor prognosis group (n=52) according to different outcomes. The subsets of ILCs (ILC1, ILC2, ILC3), interleukin (IL)-12, IL-33, IL-1β levels in peripheral blood were compared among the groups. The correlation between each index and the severity of intracranial infection and the predictive value of poor prognosis in infected patients were analyzed. Results Compared with the non-infection group, the levels of ILC2 and ILC3 in the infection group were reduced, while the levels of IL-12, IL-33 and IL-1β were increased (P < 0.05). The levels of ILC2 and ILC3 in infected patients decreased with the increase of infection severity, while the levels of IL-12, IL-33 and IL-1β increased with the increase of infection severity (P < 0.05). The levels of ILC2 and ILC3 in patients with intracranial infection werenegatively correlated with the severity of infection (r=-0.721, -0.596, P < 0.001), while the levels of IL-12, IL-33 and IL-1β were positively correlated with the severity of infection (r=0.576, 0.483, 0.553, P < 0.001). The combined prediction of peripheral blood ILC2, ILC3, IL-12, IL-33 and IL-1β for poor prognosis in infected patients had a higher AUC (0.930) and specificity (84.91%) than each index alone. Conclusion The levels of peripheral blood ILC2, ILC3, IL-12, IL-33 and IL-1β in patients with postoperative intracranial infection after hypertensive basal ganglia hemorrhage are associated with the severity of infection. The combined detection of five indicators has a good predictive value for poor prognosis in infected patients.

Objective To explore the mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in improvement of renal injury in rats with diabetic nephropathy (DN) by regulating mammalian target of rapamycin (mTOR)/p70 ribosome protein S6 kinase (S6K1)/coiled-coil myosin-like Bcl-2-interacting protein (Beclin 1) pathway. Methods The model of SD rats with DN was established by a method of high-fat diet combined with intraperitoneal injection of streptozotocin, and they were randomly divided into model group, MSC-EVs group, and MSC-EVs+MHY1485 (mTOR activator) group, with 12 rats in each group. Another 12 SD rats were normally fed for 6 weeks and then intraperitoneally injected with an equal dose of sodium citrate solution as controls. After grouping with MSC-EVs and MHY1485, blood glucose and levels of renal function indicators [blood urea nitrogen (BUN), serum creatinine (Scr), and urinary microalbumin (UmALB)] in rats were detected. HE staining was used to detect the pathological morphology of renal tissue in rats of each group; immunohistochemistry was used to detect the expression of mTOR/S6K1/Beclin 1 pathway related proteins in the renal tissues of rats in each group; the Western blot was used to detect the mTOR/S6K1/Beclin 1 pathway and autophagy-related protein expression in the renal tissues of rats in each group. Results Compared with the control group, the renal tissue morphology of rats in the model group were impaired, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, p-S6K1/S6K1 increased significantly (P < 0.05), while microtubule associated protein 1A/1B light chain 3 (LC3) Ⅱ/LC3Ⅰ, expression of Beclin 1 protein, and relative positive expression of Beclin 1 significantly reduced (P < 0.05); compared with the model group, the MSC-EVs group had less impairment in the renal tissue morphology, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, and p-S6K1/S6K1 decreased significantly (P < 0.05), while expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 increased significantly (P < 0.05); compared with the MSC-EVs group, the impairment of the renal tissue morphology was worse in the MSC-EVs+MHY1485 group, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, expression of p-mTOR/mTOR, and p-S6K1/S6K1 increased significantly (P < 0.05), while the expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 decreased significantly (P < 0.05). Conclusion MSC-EVs can enhance autophagy, reduce levels of blood glucose, Scr, BUN and urinary protein in rats with DN, alleviate renal tissue damage, and the mechanism may be achieved by inhibiting the activation of the mTOR/S6K1/Beclin 1 pathway.

Objective     To explore the safety and feasibility of preferential manual bronchoplasty in single-port video-assisted thoracoscopic surgery (VATS) upper lobectomy. Methods    The clinical data of 457 patients with non-small cell lung cancer who underwent single-port VATS lobectomy in the Department of Thoracic Surgery of Peking University First Hospital from March 2020 to March 2022 were retrospectively analyzed. The patients were divided into a preferential manual bronchoplasty group and a traditional single-port VATS lobectomy group with a 1 : 1 propensity score matching for further research. Results     A total of 204 patients were matched, and there were 102 patients in each group. There were 50 males and 52 females aged 62.2±10.1 years in the preferential bronchoplasty group, and 49 males and 53 females aged 61.2±10.7 years in the traditional single-port VATS group. The preferential bronchoplasty group had shorter surgical time (154.4±37.0 min vs. 221.2±68.9 min, P<0.01), less bleeding (66.5±116.9 mL vs. 288.6±754.5 mL, P=0.02), more lymph node dissection (19.8±7.5 vs. 15.2±4.7, P<0.01), and a lower conversion rate to multi-port or open surgery (2.3% vs. 13.8%, P=0.04) in left upper lobe resection. In the right upper lobe resection surgery, there was no statistical difference in postoperative results between two groups. There was no perioperative death or occurrence of bronchopleural fistula in both groups. Conclusion    Compared with traditional single-port VATS upper lobectomy, preferential bronchoplasty has similar safety and feasibility. In addition, priority bronchoplasty in left upper lobectomy has the advantages of shorter surgical time, less bleeding, more lymph node dissection, and lower conversion rate to multi-port or open surgery.

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

【Objective】 To investigate the establishment of multi-center haemovigilance (HV) and the monitoring of adverse reactions to blood donation (ARBD), in order to provide basis for the management of blood donors. 【Methods】 The operation of HV was investigated by questionnaire. The total number of blood donations (including plateletpheresis) and ARBD cases occurred in each blood center from 2014 to 2018 were analyzed. 【Results】 Among the 24 blood centers in this survey, only nine got HV operated. The incidence of ARBD of 19 blood centers that fulfilled the questionnaire was in the range of (0.003~1.151) %. The change trend of number and incidence of ARBD cases were indeterminate. 【Conclusion】 Most blood centers did not got HV established. The incidence of ARBD varied greatly and was indeterminate. The application of HV should be further improved to strengthen ARBD management.

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.