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 compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.

Objective:To investigate the efficacy and safety of nerve decompression surgery through the lateral-rectus approach for sacral plexus nerve injury after sacral fracture fixation.Methods:A retrospective study was conducted to analyze the 10 patients with combined sacral plexus nerve injury after sacral fracture fixation who had been admitted to Department of Orthopedics, Xiangya Hospital between May 2022 and May 2023. There were 2 males and 8 females with an age of 16.5 (15.0, 26.3) years. At the time of injury, the patients had been clearly diagnosed as sacral fracture combined with sacral plexus nerve injury. By the Denis classification of sacral fractures: 7 cases of type Ⅱ and 3 cases of type Ⅲ; sacral plexus nerve injury sites: 1 case of L 4, 8 cases of L 5, 7 cases of S 1, and 2 cases of S 2. All of them were treated with reduction and internal fixation via the posterior approach within 2 weeks after injury, but after surgery their manifestations of sacral plexus nerve injury still persisted which were confirmed by CT, magnetic resonance imaging and neuromuscular electromyography. Therefore, at (4.0±2.3) months after internal fixation, all patients were treated with nerve decompression surgery through the lateral-rectus approach. The operative time, intraoperative bleeding, length of hospitalization, Gibbons nerve damage score and neurological recovery at the last follow-up were recorded. Results:In the 10 patients, the operative time was (112.0±21.5) min, intraoperative bleeding (215.0±91.3) mL, and length of hospitalization 7.0 (6.0, 8.5) d. Intraoperatively, sacral plexus nerve compression was found in 9 cases (6 cases of nerve compression and pulling due to fracture displacement, 3 cases of nerve entrapment due to soft tissue scar adhesion), and 1 case of nerve root avulsion injury. No other intraoperative complications occurred. The 10 patients were followed up for (9.2±2.3) months after surgery. At the last follow-up, the Gibbons score for the 10 patients improved from preoperative 3.0 (3.0, 3.3) points to 1.0 (1.0, 2.0) point, and their British Medical Research Council (BMRC) nerve injury grading was improved from the preoperative grade 0.0 (0.0, 1.3) to grade 3.5 (2.8, 4.0) (1 case of M5, 4 cases of M4, 4 cases of M3, and 1 case of M2).Conclusion:The lateral-rectus approach is effective and safe for exploration and decompression of the sacral plexus nerve in patients combined with sacral plexus nerve injury despite sacral fracture fixation.

Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.

Objective:To explore the change in cerebral blood flow when healthy subjects swallow hot and ice water, and to verify the sensitivity of functional near-infrared spectroscopy (fNIRS) in identifying liquid temperatures while swallowing as a basis for applying it in diagnosis and intervention.Methods:Sixteen healthy subjects swallowed hot and ice water in randomized order while the process was recorded using fNIRS. The activation at rest and when swallowing hot and ice water was compared pairwise.Results:Compared with the resting state, 19 channels were activated during the swallowing of the hot and ice water. The common activated areas were S1, M1, PMC, SMA, Wernicke′s area, the somatosensory association cortex, the visual association cortex and the frontal eye field. However, the dorsal lateral prefrontal cortex was activated only when swallowing hot water, and the subcentral area was activated only when swallowing ice water. The SMA and PMC were significantly more activated when swallowing hot water than ice water.Conclusions:Multiple brain regions are activated and participate in regulating swallowing. The PMC and SMA areas can distinguish hot water from ice water swallowing.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People

OBJECTIVE：To analyze the effects of mangiferin （MGF）on glucose and lipid metabolism in insulin resistance （IR）HepG2 cells，and to explore the potential mechanism. METHODS ：Using human hepatoma HepG 2 cells as research objects ， 1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG 2 cell model. Using metformin hydrochloride as positive control ，the effects of low-concentration ，medium-concentration and high-concentration MGF （125，250，500 μmol/L）on the corrected glucose consumption ，the contents of triglyceride （TG）and total cholesterol （TC）in IR-HepG 2 cells were detected. The mRNA expression of APN ，AdipoR2，APPL1，AMPK in the upstream of AMPK signaling pathway and IRS- 1，Akt and GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was detected by Western blot assay. RESULTS ：Compared with control group ，corrected glucose consumption ，mRNA expression of APN，AdipoR2，APPL1，AMPK，IRS-1 and GLUT 4，as well as the phosphorylation level of AMPK protein were decreased significantly in model group ，while the contents of TG and TC were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ， corrected glucose consumption ， mRNA expression of APN （except for MGF medium-concentration and high-concentration groups ），AdipoR2，APPL1，AMPK（except for MGF medium-concentration and high-concentration groups ）， IRS-1（except for MGF medium-concentration and high-concentration groups ），Akt（except for positive control group ），GLUT4 （except for MGF high-concentration group ）were increased significantly in administration groups ，while the contents of TG and TC were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Mangiferin may activate APN ，which is the upstream target of pathway ，and then regulate AMPK signaling pathway ，so as to promote glucose uptake of IR-HepG 2 cells，reduce TG and TC contents，and improve IR and abnormal glucose and lipid metabolism.

Objective To study the underlying mechanisms through which uric acid upregulates local renin-angiotensin system in adipocytes. Methods The primary cultured rat adipocytes were administered with 0, 1, 5, 10, and 15 mg/dl uric acid for 0, 12, 24, 48, and 72 h. Some of the pre-adipocytes were infected with siRNA-TLR2 or its negative control before differentiation. Then infected mature adipocytes were treated with 10 mg/dl uric acid for 48 h. After that procedure, mRNA levels of TLR2, TNF-α, IL-6, MCP-1, AGT, ACE1, AT1R, and AT2R were detected with real-time PCR method. The protein levels of TLR2 and NF-κB were detected by Western blotting. The concentrations of angiotensinⅡ( Ang Ⅱ) in the conditioned medium or cell lysate were measured using ELISA method. Results The mRNA levels mRNA of TLR2 increased in parallel with uric acid concentration. Moreover, it also increased with the time. By contrast, TLR2 mRNA expression decreased at 72 h. Uric acid increased levels of TNF-α, IL-6, and MCP-1 in adipocytes. It was also found that uric acid upregulated RAS components, including AGT, ACE1, AT1R, AT2R, and AngⅡ. However, siRNA-TLR2 infection significantly reduced the levels of TLR2 and NF-κB. As a result, both inflammatory cytokines and RAS components were significantly decreased in adipocytes. Conclusion Uric acid up-regulates RAS expression partially via TLR2 inflammatory signaling pathway in adipocytes.

Objective To investigate the clinical efficacy and safety of individualized preconditioning in ABO-incompatible living donor kidney transplantation.Methods A series of 36 living donor kidney transplants across a wide range of ABO blood group incompatibilities using individualized preconditioning protocols were performed from September 2014 to June 2017.Preconditioning included oral immunosuppressants with or without the administration of rituximab,PE or DFPP.Medical records and electronic databases were reviewed for isoagglutinin titers,patient and graft survivals,graft function,rejections,infections as well as surgical complications.Results Of 30 ABO blood group incompatibilities,there were 6 cases of AB to A,2 cases of AB to B,4 cases of A to B,3 cases of B to A,13 cases of A to O (13),and 8 cases of B to O.Median initial ABO antibody titers were 1∶32 (1∶2-1∶256) (IgM) and 1 ∶ 8 (0-1∶64) (IgG),respectively.Individualized preconditioning included oral immunosuppressants alone (10 cases),oral immunosuppressants + PE (4 cases),oral immunosuppressants + PE + DFPP (1 case),oral immunosuppressants + rituximab + PE (16 cases),oral immunosuppressants + rituximab + DFPP (2 cases),and oral immunosuppressants + rituximab + PE+ DFPP (3 cases).After individualized preconditioning,an acceptable ABO antibody titer (≤1 ∶ 16) was obtained on the day of transplantation.Median follow-up duration was 12 months (1-33).Graft and patient survival rate was 94.4％ (34/36) and 100％ (36/36) respectively.Median value of serum creatinine at one year posttransplantation was 89 μmol/L,and eGFR was (81.07 mL/min/1.73 m2).In total,there was one episode of urinary tract infection and upper gastrointestinal tract hemorrhage,two cases of hyperacute rejection (leading to graft loss),acutecelluar-mediated rejection,delayed graft function,bone marrow suppression and pneumonia,and 3 cases of acute antibody-mediated rejection and wound fat liquefaction,respectively.Conclusion Our initial experience indicates that individualized preconditioning protocol based on initial ABO antibody titers is safe and technically feasible,and leads to excellent short-term survival of ABOi living donor kidney transplantation.