[Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions(2): to improve the extrapolation of efficacy].

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 31st 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.

[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

[Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions (1): to improve the validity of real-world evidence].

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 31st 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.

[Living-donor intestinal transplantation].

Due to advances in surgical techniques, perioperative care, and new immunosuppressive agents, intestinal transplantation has become a valid therapeutic choice for chronic intestinal failure. Intestinal transplantation has been performed most commonly using deceased donation, while less than 2% of which have been from living donation. Living donor intestinal transplantation obtaining a segmental intestinal graft, usually from close relatives. Preliminary results show that acute/chronic rejection rates, postoperative opportunistic infections, and graft versus host disease are significantly reduced after living donor intestinal transplantation, contributing to improved graft and patient survivals. Due to a severe shortage of organ donation, especially in children, living donor intestinal transplantation has increasingly become an important treatment option for patients with chronic intestinal failure in China.

[Estimation of COVID-19 incidence in Shanghai under optimized epidemic prevention and control strategies].

Objective: To quantitatively estimate the incidence of COVID-19 in different backgrounds, including vaccination coverage, non-pharmacological interventions (NPIs) measures, home quarantine willingness and international arrivals, and the demands of healthcare resource in Shanghai in the context of optimized epidemic prevention and control strategies. Methods: Based on the natural history of 2019-nCoV, local vaccination coverage and NPI performance, an age-structured Susceptible-Exposed-Infections-Removed (SEIR) epidemic dynamic model was established for the estimation of the incidence of COVID-19 and demand of hospital beds in Shanghai by using the data on December 1, 2022 as the basis. Results: Based on current vaccination coverage, it is estimated that 180 184 COVID-19 cases would need treatment in hospitals in Shanghai within 100 days. When the booster vaccination coverage reaches an ideal level, the number of the cases needing hospitalization would decrease by 73.20%. School closure or school closure plus workplace closure could reduce the peak demand of regular beds by 24.04% or 37.73%, respectively, compared with the situation without NPI. Increased willingness of home quarantine could reduce the number of daily new cases and delay incidence peak of COVID-19. The number of international arrivals has little impact on the development of the epidemic. Conclusions: According to the epidemiological characteristics of COVID-19 and the actual situation of vaccination in Shanghai, the incidence of COVID-19 and health resource demand might be reduced by increasing vaccination coverage and early implementation of NPI.

[The application value of deep learning image reconstruction on improving image quality and evaluating the Qanadli embolism index of dual low-dose CT pulmonary angiography].

Objective: To compare the image quality and Qanadli embolism index between deep learning image reconstruction (DLR) and adaptive statistical iterative reconstruction-veo (ASiR-V) in dual low-dose CT pulmonary angiography (CTPA) with low contrast agent dose and low radiation dose. Methods: Eighty-eight patients who underwent dual low-dose CTPA in the radiology department of the affiliated hospital of Xuzhou Medical University from October 2020 to March 2021 were retrospectively analyzed, including 44 males and 44 females, aged from 11 to 87 years (61±15 years). The CTPA examination were performed using 80 kV tube voltage and 20 ml contrast agent. The raw data were reconstructed using standard kernel DLR high level (DL-H) and ASiR-V reconstruction, respectively. The patients were divided into standard kernel DL-H group (n=88, 33 cases of positive embolism) and ASiR-V group (n=88, 36 cases of positive embolism). The CT value, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), subjective image quality score, Qanadli embolism index, positive rate and positive Qanadli embolism index were compared between the two groups. Results: There were no statistically significant differences in CT values of the main pulmonary artery, the right pulmonary artery and the left pulmonary artery between the standard kernel DL-H group and ASiR-V group [(405.8±111.7) vs (404.0±112.0) HU, (412.9±113.1) vs (411.5±112.2) HU, (418.1±119.9) vs (415.4±118.0) HU, respectively;all P>0.05)]. The image noise of the main pulmonary artery, the right pulmonary artery and the left pulmonary artery in the standard kernel DL-H group was significantly lower than the ASiR-V group(16.6±4.7 vs 28.1±4.8, 18.3±6.1 vs 29.8±4.9, 17.6±5.6 vs 28.4±4.7, respectively;all P<0.001). The SNR and CNR of the main pulmonary artery, the right pulmonary artery and the left pulmonary artery in the standard kernel DL-H group were significantly higher than the ASiR-V group(SNR: 25.5±7.1 vs 14.5±3.9, 23.9±7.2 vs 13.9±3.4, 24.9±7.4 vs 14.8±4.1, CNR: 21.6±6.6 vs 12.3±3.9, 20.2±6.7 vs 11.8±3.4, 21.2±6.9 vs 12.6±4.1, respectively;all P<0.001). The subjective image quality score of the standard kernel DL-H group was significantly higher than the ASiR-V group (4.6 vs 3.8, P<0.001). There were no significant difference in the Qanadli embolism index, positive rate and positive Qanadli embolism index between the two groups (all P>0.05). Conclusion: Compared with ASiR-V reconstruction algorithms group, standard kernel DL-H reconstruction algorithms can significantly improve the image quality of dual low-dose CTPA.

[Establishment and application of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns].

Objective: To investigate the scientificity and feasibility of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns. Methods: A retrospective observational study was conducted. The total burn area of 30%-100% total body surface area (TBSA) and body weight of 6-50 kg in 433 pediatric patients (250 males and 183 females, aged 3 months to 14 years) with extensive burns who met the inclusion criteria and admitted to the burn departments of 72 Class A tertiary hospitals were collected. The 6 319 pairs of simulated data were constructed after pairing each body weight of 6-50 kg (programmed in steps of 0.5 kg) and each total burn area of 30%-100% TBSA (programmed in steps of 1%TBSA). They were put into three accepted pediatric rehydration formulae, namely the commonly used domestic pediatric rehydration formula for burn patients (hereinafter referred to as the domestic rehydration formula), the Galveston formula, and the Cincinnati formula, and the two rehydration formulae for pediatric emergency, namely the simplified resuscitation formula for emergency care of patients with extensive burns proposed by the World Health Organization's Technical Working Group on Burns (TWGB, hereinafter referred to as the TWGB formula) and the pediatric ten-fold rehydration formula proposed by the author of this article--rehydration rate (mL/h)=body weight (kg) × 10 (mL·kg-1·h-1) to calculate the rehydration rate within 8 h post injury (hereinafter referred to as the rehydration rate). The range of the results of the 3 accepted pediatric rehydration formulae ±20% were regarded as the reasonable rehydration rate, and the accuracy rates of rehydration rate calculated using the two pediatric emergency rehydration formulae were compared. Using the maximum burn areas (55% and 85% TBSA) corresponding to the reasonable rehydration rate calculated by the pediatric ten-fold rehydration formula at the body weight of 6 and 50 kg respectively, the total burn area of 30% to 100% TBSA was divided into 3 segments and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae in each segment were compared. When neither of the rehydration rates calculated by the 2 pediatric emergency rehydration formulae was reasonable, the differences between the two rehydration rates were compared. The distribution of 433 pediatric patients in the 3 previous total burn area segments was counted and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae were calculated and compared. Data were statistically analyzed with McNemar test. Results: Substitution of 6 319 pairs of simulated data showed that the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula was 73.92% (4 671/6 319), which was significantly higher than 4.02% (254/6 319) of the TWGB formula (χ2=6 490.88,P<0.05). When the total burn area was 30%-55% and 56%-85% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula were 100% (2 314/2 314) and 88.28% (2 357/2 670), respectively, which were significantly higher than 10.98% (254/2 314) and 0 (0/2 670) of the TWGB formula (with χ2 values of 3 712.49 and 4 227.97, respectively, P<0.05); when the total burn area was 86%-100% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula and the TWGB formula were 0 (0/1 335). When the rehydration rates calculated by the 2 pediatric emergency rehydration formulae were unreasonable, the rehydration rates calculated by the pediatric ten-fold rehydration formula were all higher than those of the TWGB formula. There were 93.07% (403/433), 5.77% (25/433), and 1.15% (5/433) patients in the 433 pediatric patients had total burn area of 30%-55%, 56%-85%, and 86%-100% TBSA, respectively, and the accuracy rate of the rehydration rate calculated using the pediatric ten-fold rehydration formula was 97.69% (423/433), which was significantly higher than 0 (0/433) of the TWGB formula (χ2=826.90, P<0.05). Conclusions: The application of the pediatric ten-fold rehydration formula to estimate the rehydration rate of pediatric patients after extensive burns is more accurate and convenient, superior to the TWGB formula, suitable for application by front-line healthcare workers that are not specialized in burns in pre-admission rescue of pediatric patients with extensive burns, and is worthy of promotion.

[Real-world evidence and randomized controlled trials: the initiation, implementation, progress interpretation and revelation of RCT DUPLICATE (part 1)].

In recent years, researchers, pharmaceutical companies, and political makers gradually using more real-world data (RWD) to produce real-world evidence (RWE) for policy-making. A research team of Harvard University launched the RCT DUPLICATE project in 2018, aiming to replicate 30 randomized controlled trials using the medical claims database in order to explore methods for quantifying the efficacy-effectiveness gap and explain its potential sources, to enhance the credibility of the RWE. This paper reviews the background of RCT DUPLICATE Initiative, highlights the research purposes, research design and implementation process of the RCT DUPLICATE Initiative, to help domestic scholars better understand the scope and application value of RWE.

[Real-world evidence and randomized controlled trials: the initiation, implementation, progress interpretation and revelation of RCT DUPLICATE (part 2)].

With the promotion and application of big medical data, non-interventional real-world evidence (RWE) has been used by regulators to assess the effectiveness of medical products. This paper briefly introduces the latest progress and research results of the RCT DUPLICATE Initiative launched by the research team of Harvard University in 2018 and summarizes relevant research experience based on the characteristics of China's medical service to provide inspiration and reference for domestic scholars to conduct related RWE research in the future.

[The value of a nomogram based on clinical data and contrast enhanced CT radiomics in the preoperative prediction of Epstein-Barr virus-associated gastric carcinoma].

Objective: To explore the value of a nomogram based on clinical data and enhanced CT radiomics in the prediction of Epstein-Barr virus-associated gastric carcinoma(EBVaGC). Methods: The data of 136 patients, including 100 males and 36 females, aged [M (Q1, Q3)] 65 (53, 71) years, with gastric cancer confirmed by surgery and pathology were retrospectively analyzed. According to Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization, those patients were divided into Epstein-Barr virus (EBV) positive group (n=32) and EBV negative group (n=104). All patients underwent multi-phase enhanced CT scanning before surgery and randomly assigned to the training group (n=95) and validation group (n=41) in a ratio of 7︰3. MaZda software was used to extract radiomics features of enhanced CT images. The intra-group correlation coefficient (ICC), variance analysis and minimum absolute shrinkage and selection algorithm (LASSO) regression were used to reduce the dimensionality of the radiomics features, and then the radiomics score (Radscore) was calculated. The nomogram model was based on combined clinical data, morphological features and Radscore. The predictive power of the nomogram was evaluated according to the area under the receiver operating characteristic curve (AUC), and the net clinical benefit of the nomogram was evaluated by the decision curve and calibration curves were drawn according to the data of the training group and the validation group to analyze the consistency of the nomogram model. Results: After selection, six optimal radiomics features were obtained, including Mean, Skewness, S(1, 0) Sum entropy, S(1, 1) Contrast, 99% percentile and S(2, 2)Angular second moment. Radscore of EBV positive group were higher than that of the EBV negative group (training group: 3.78±0.83 vs 2.80±0.98; validation group: 3.81±0.47 vs 2.94±0.95) (both P<0.05) both in the training group and validation group. The AUC of the radiomics model in training group and validation group were 0.773(95%CI:0.612-0.962)and 0.792(95%CI:0.597-0.927)respectively,and the sensitivity and specificity were 63.6% and 93.1%, 70.0% and 87.1%, respectively. The AUC of the nomogram model based on clinical data and radiomics in the training group and the validation group were 0.883(95%CI:0.644-0.984) and 0.851(95%CI:0.715-0.996), respectively. The nomogram model showed superior predictive performance (both P<0.05). Conclusion: The nomogram model based on clinical data and radiomics has better efficacy in the prediction of Epstein-Barr virus associated gastric cancer.

[Effects of methacrylic anhydride gelatin hydrogel loaded with silver and recombinant human basic fibroblast growth factor on deep partial-thickness burn wounds in rabbits].

Objective: To investigate the effects of methacrylic anhydride gelatin (GelMA) hydrogel loaded with silver and recombinant human basic fibroblast growth factor (rh-bFGF) on deep partial-thickness burn wounds in rabbits. Methods: The experimental research method was adopted. Low-concentration GelMA materials, medium-concentration GelMA materials and high-concentration GelMA materials containing different concentrations of methacrylic anhydride (MA) were prepared, after adding photoinitiator, low-concentration GelMA hydrogels, medium-concentration GelMA hydrogels, and high-concentration GelMA hydrogels were obtained, respectively. The nuclear magnetic resonance spectroscopy was performed to detect the hydrogen nuclear magnetic resonance spectra of the above-mentioned three concentrations of GelMA materials, and to calculate the degree of substitution according to the spectrum diagram. The three-dimensional microstructure and pore size of 3 types of above-mentioned GelMA hydrogels were detected by field emission scanning electron microscopy (FESEM), with 9 samples measured. According to the selected concentration of MA, ten kinds of solutions of GelMA with different concentration of silver (silver-containing GelMA) were synthesized, and the silver-containing GelMA solution of each concentration was divided into three parts, and then exposed to ultraviolet light lasting for 20, 25, and 35 s, respectively. After adding photoinitiator,the corresponding silver-containing GelMA hydrogels were obtained. The residual degradation rate of silver-containing GelMA hydrogel with different photocrosslinking times was detected by collagenase degradation method at degradation of 12, 24, 36, and 48 h; and the time required for complete degradation was detected, and the sample number was 5. The inhibition zone diameter of GelMA hydrogel under above screened photocrosslinking times containing 10 concentrations of silver against Staphylococcus aureus was measured to reflect its antibacterial ability, and the sample numbers were all 5. The silver-containing GelMA hydrogel with statistical significance compared with the antibacterial circle diameter of the silver-containing GelMA hydrogel containing the lowest concentration (no silver) was considered as having antibacterial activity. The three-dimensional microstructure and pore size of the silver-containing GelMA hydrogels with antibacterial activity and the lowest drug concentration selected were detected by FESEM, and the sample numbers were all 9. The freeze-dried alone GelMA hydrogel and the freeze-dried silver-containing GelMA hydrogel were soaked in phosphate buffer solution for 24 h, respectively, then the swelling rate of the two GelMA hydrogel were calculated and compared by weighing method, and the sample number was 5. GelMA hydrogel containing silver and rh-bFGF, namely compound hydrogel for short, was prepared according to the preliminary experiment and the above experimental results. The appearance of the composite hydrogel was observed in general, and its three-dimensional microstructure and pore size were detected by FESEM. The deep partial-thickness burn wound was made on the back of 30 rabbits (aged 4-6 months, female half and half). Meanwhile, with the rabbit head as the benchmark, the wounds on the left side of the spine were treated as composite hydrogel treatment group, and the wounds on the right side were treated as gauze control group, and which were treated accordingly. On post injury day (PID) 3, 7, 14, 21, and 28, the healing of wounds in the two groups was observed. On PID 7, 14, 21, and 28, the wound healing area was recorded and the healing rate was calculated, with a sample number of 30. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and independent sample t test. Results: The substitution degree among low-concentration GelMA materials, medium-concentration GelMA materials, and high-concentration GelMA materials was significantly different (F=1 628.00, P<0.01). The low-concentration GelMA hydrogel had a loose and irregular three-dimensional spatial network structure with a pore size of (60±17) µm; the medium-concentration GelMA hydrogel had a relatively uniform three-dimensional spatial network and pore size with a pore size of (45±13) µm; the high-concentration GelMA hydrogel had the dense and disordered three-dimensional spatial network with a pore size of (25±15) µm, the pore sizes of 3 types of GelMA hydrogels were significantly differences (F=12.20, P<0.01), and medium concentration of MA was selected for the concentration of subsequent materials. The degradability of silver-containing GelMA hydrogels with different concentrations of the same photocrosslinking time was basically same. The degradation residual rates of silver-containing GelMA hydrogels with 20, 25, and 35 s crosslinking time at 12 h were (74.2±1.7)%, (85.3±0.9)%, and (93.2±1.2)%, respectively; the residual rates of degradation at 24 h were (58.3±2.1)%, (65.2±1.8)%, and (81.4±2.6)%, respectively; the residual rates of degradation at 36 h were (22.4±1.9)%, (45.2±1.7)%, and (68.1±1.4)%, respectively; the residual rates of degradation at 48 h were (8.2±1.7)%, (32.4±1.3)%, and (54.3±2.2)%, respectively, and 20, 25, and 30 s photocrosslinking time required for complete degradation of silver-containing GelMA hydrogels were (50.2±2.4), (62.4±1.4), and (72.2±3.2) h, and the difference was statistically significant (F=182.40, P<0.01), 25 s were selected as the subsequent photocrosslinking time. The antibacterial diameters of 10 types of silver-containing GelMA hydrogels against Staphylococcus aureus from low to high concentrations were (2.6±0.4), (2.5±0.4), (3.2±0.4), (12.1±0.7), (14.8±0.7), (15.1±0.5), (16.2±0.6), (16.7±0.5), (16.7±0.4), and (16.7±0.6) mm, respectively, and which basically showed a concentration-dependent increasing trend, and the overall difference was statistically significant (F=428.70, P<0.01). Compared with the silver-containing GelMA hydrogel with the lowest concentration, the antibacterial circle diameters of other silver-containing GelMA hydrogels with antibacterial ability from low to high concentration were significantly increased (with t values of 26.35, 33.84, 43.65, 42.17, 49.24, 55.74, and 43.72, respectively, P<0.01). The silver-containing GelMA hydrogel with the antibacterial diameter of (12.1±0.7) mm had the lowest antibacterial activity against Staphylococcus aureus and the lowest drug loading concentration, and the concentration of silver was selected for the concentration of subsequent materials. The microscopic morphology of the silver-containing GelMA hydrogel containing silver element with a pore size of (45±13) µm had a regular and linear strip-like structure. After soaking for 24 h, the swelling ratio of silver-containing GelMA hydrogel was similar to that of alone GelMA hydrogel. The composite hydrogel was colorless, clear and transparent, and its three-dimensional microstructure was a regular and uniform grid, with a filament network structure inside, and the pore size of (40±21) µm. On PID 3, a large amount of necrotic tissue and exudate of rabbit wound in composite hydrogel group were observed, and scattered scabs, a small amount of necrotic tissue and exudate of rabbit wound in gauze control group were observed. On PID 7, the area of rabbit wound in composite hydrogel group was significantly reduced, and adhesion of rabbit wound and gauze in gauze control group was observed. On PID 14, In composite hydrogel group, the rabbit wound surface was ruddy, and the growth of granulation tissue was observed, and in gauze control group, the rabbit wound base was pale, and the blood supply was poor. On PID 21, the rabbit wounds in composite hydrogel group healed completely, and rabbit wound in gauze control group had healing trend. On PID 28, new hair could be seen on rabbit wound surface in composite hydrogel group; oval wound of rabbit in gauze control group still remained. On PID 7, 14, 21, and 28, the wound healing areas of rabbit in composite hydrogel group were significantly larger than those in gauze control group (with t values of 2.24, 4.43, 7.67, and 7.69, respectively, P<0.05 or P<0.01). Conclusions: The medium-concentration GelMA hydrogel has good physical and chemical properties in terms of swelling and degradability. The screened silver-containing GelMA hydrogels had the lowest antibacterial activity and the lowest drug loading concentration. Composite hydrogel can significantly shorten the healing time of deep partial-thickness burn wounds in rabbits.

[Artificial intelligence-based literature data warehouse for vaccine safety].

Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.

[Establishment and application of the tenfold rehydration formula for emergency resuscitation of adult patients after extensive burns].

Objective: To explore the scientificity and feasibility of the tenfold rehydration formula for emergency resuscitation of adult patients after extensive burns. Methods: A retrospective observational study was conducted. The total burn area (30%-100% total body surface area (TBSA)) and body weight (45-135 kg) of 170 adult patients (135 males and 35 females, aged (42±14) years) with extensive burns admitted to the Fourth Medical Center of PLA General Hospital from December 2016 to December 2019 were collected. The 6 461 pairs of simulated data obtained after pairing each body weight in 45 to 135 kg (programmed in steps of 1 kg) with each area in 30% to 100% TBSA (programmed in steps of 1%TBSA) were plugged into four recognized rehydration formulas--Parkland's formula, Brooke's formula, the 304th PLA Hospital formula, and the Third Military Medical University formula and two emergency rehydration formulas--the simplified first aid resuscitation plan for extensive burn patients proposed by the World Health Organization's Technical Working Group on Burns (TWGB, hereinafter referred to as the TWGB formula) and the tenfold rehydration formula proposed by the author of this article to calculate the rehydration rate within 8 hours after injury (hereinafter referred to as the rehydration rate), with results being displayed by a programming step of 10%TBSA for the total burn area. Taking the calculation results of four recognized rehydration formulas as the reasonable rehydration rate, the accuracy of rehydration rates calculated by two emergency rehydration formulas were calculated and compared. The body weight of 45-135 kg was divided into three segments by the results of maximum body weight at a reasonable rehydration rate calculated by the tenfold rehydration formula when the total burn area was 30% and 100% TBSA, respectively. The accuracy of rehydration rate calculated by two emergency rehydration formulas in each body weight segment was compared. When the rehydration rates calculated by two emergency rehydration formulas were unreasonable, the differences in rehydration rates between the two were compared. Statistical distribution of the aforementioned three body weight segments in the aforementioned 170 patients was counted. Using the total burn area and body weight data of the aforementioned 170 patients, the accuracy of rehydration rate calculated by two emergency rehydration formulas was calculated and compared as before. Data were statistically analyzed with McNemar test. Results: When the total burn area was 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% TBSA, respectively, and the body weight was 45-135 kg, the rehydration rates calculated by two emergency rehydration formulas did not exceed the maximum of the calculated results of four recognized rehydration formulas; the rehydration rate calculated by the TWGB formula did not change accordingly with total burn area, while the rehydration rate calculated by the tenfold rehydration formula did not change accordingly with body weight. Substituting 6 461 pairs of simulated data showed that the accuracy of rehydration rate calculated by the tenfold rehydration formula was 43.09% (2 784/6 461), which was significantly higher than 2.07% (134/6 461) of the TWGB formula, χ2=2 404.80, P<0.01. When the body weights were 45-62 kg and 63-93 kg, the accuracy rates of rehydration rate calculated by the tenfold rehydration formula were 100% (1 278/1 278) and 68.42% (1 506/2 201), respectively, which were significantly higher than 0 (0/1 278) and 0.05% (1/2 201) of the TWGB formula, χ2=1 276.00, 1 501.01, P<0.01; when the body weight was 94-135 kg, the accuracy rate of rehydration rate calculated by the tenfold rehydration formula was 0 (0/2 982), which was significantly lower than 4.46% (133/2 982) of the TWGB formula, χ2=131.01, P<0.01. When the rehydration rates calculated by two emergency rehydration formulas were both unreasonable, the rehydration rate calculated by the tenfold rehydration formula was greater than that calculated by the TWGB formula in most cases, accounting for 79.3% (2 808/3 543). Among the 170 patients, the proportions of those weighing 45-62, 63-93, and 94-135 kg were 25.29% (43/170), 65.88% (112/170), and 8.82% (15/170), respectively. Among the 170 patients, the accuracy rate of rehydration rate calculated by the tenfold rehydration formula was 69.41% (118/170), which was significantly higher than 3.53% (6/170) of the TWGB formula, χ2=99.36, P<0.01. Conclusions: Applying the tenfold rehydration formula to calculate the emergency rehydration rate in adults after extensive burns is simpler than four recognized rehydration formulas, and is superior to the TWGB formula. The tenfold rehydration formula is suitable for the front-line medical staffs that are not specialized in burns in pre-admission rescue of adult patients with extensive burns, which is worth popularizing.

[Study on changes in hepatitis B incidence in China, 1990-2017].

Objective: To analyze the changes in the morbidity and mortality of hepatitis B in China from 1990 to 2017, and provide evidence for prevention and control of hepatitis B. Methods: The reported incidence and death data of hepatitis B from the Data-Center of China Public Health Science and demographic data from the National Bureau of Statistics were used, Excel 2016 was used to establish the databases of reported hepatitis B cases and deaths, respectively. The Joinpoint regression model was used through Joinpoint software 4.8.0.1 to estimate the average annual percent change of annual reported incidence and mortality of hepatitis B in different age groups and provinces in China from 1990 to 2017 in order to further explore the trend of hepatitis B incidence. Software R 3.6.2 was used for statistical analysis and data visualization. Results: A total of 20 793 233 hepatitis B cases were reported from January 1990 to December 2017 in China with average annual reported incidence of 58.19/100 000. The average annual reported incidence appeared highest in age group 25-29 years (119.67/100 000) and the annual reported incidence increased in group aged 45 years and above. Besides, the reported case fatality rate reached the highest in group aged 85 years and above (2.26/1 000). The reported incidence showed increasing trends in 23 provinces (P<0.05), stable in 7 provinces (P>0.05), and decreasing in 2 provinces (P<0.05). Conclusions: The report of hepatitis B was mainly from adult population in China, and the reported incidence of hepatitis B in this population was in increase. In some provinces of the eastern China where immunization measures have been in place and the treatment level is relatively high, the incidence of hepatitis B has been leveled off; the incidences in most provinces in western China are still in increase. Therefore, more targeted prevention and control strategies should be taken in different provinces.

The cross-polarization scattering system for the magnetic fluctuation measurement in the Experimental Advanced Superconducting Tokamak.

The cross-polarization scattering (CPS) system for magnetic fluctuation measurements in the Experimental Advanced Superconducting Tokamak (EAST) has been designed and installed. Different from the Doppler reflectometer (DR) system, the CPS system detects the perpendicular polarization of the electromagnetic wave induced by magnetic fluctuations B̃. The CPS system in the EAST has been developed from the existing Doppler reflectometer system, and they are integrated together for simultaneous measurement of magnetic and density fluctuations. Ray-tracing simulations are used to calculate the scattering locations and the wavenumber coverage of the magnetic fluctuation for CPS. In the experiments, the CPS and DR system data were different in Doppler shift, amplitude, and spectrum broadening. In this article, the hardware design, the ray tracing, and the preliminary results of the system in the EAST are presented.

[Protective effect and mechanism of mild hypothermia on liver injury after cardiopulmonary resuscitation in pigs].

Objective: To investigate the effect of mild hypothermia therapy on liver after cardiopulmonary resuscitation. Methods: Thirty-three inbred Chinese Wuzhishan (WZS) minipigs, weighted (28±2) kg, were used to establish a ventricular fibrillation model. And 30 animals survived after cardiopulmonary resuscitation reached basic life support. The surviving animals were randomly divided into two groups: mild hypothermia group (group M, n=15) and conventional treatment group (group C, n=15). All the animals were observed for 24 hours. Blood samples were extracted at baseline, 0.5, 1, 2, 4, 6, 12 and 24 h after successful resuscitation. The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected at the time points. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α). The data were compared between the two groups, LSD test was used when the variance was homogeneous, and Tamhane T2 test was used when the variance was uneven. Results: Eleven pigs (73.3%) in the group M and 8(53.3%) in the group C survived at 24 h after successful resuscitation, with no statistically significant difference between the two groups (χ(2)=1.229, P=0.225). After successful resuscitation, the AST, ALT increased in both group but less in M group (all P<0.05). After successful resuscitation, the concentrations of TFN-α and IL-6 in the blood increased in both groups, reached the peak at 4h, and then decreased gradually. The concentrations of TFN-α in group M were lower than those in group C at 0.5, 2, 4 and 6 h after successful resuscitation (t=0.01, 0.01, 0.87, 0.86, all P<0.05). The concentrations of IL-6 in the group M were lower than those in group C at 0.5, 1, 2 and 4 h after successful resuscitation (t=0.23, 0.78, 0.11, 0.80, all P<0.05). Conclusions: After successful resuscitation, the release of inflammatory mediators, such as TNF-α and IL-6, and cell apoptosis may involve in liver ischemia reperfusion injury. After successful resuscitation, the liver undergoes ischemia-reperfusion injury, which may be related to the release of inflammatory mediators such as TNF-α and IL-6. Mild hypothermia therapy can prevent the release of TNF-α, IL-6 to reduce the degree of liver damage after resuscitation.

[Changes of insulin secretion and its signal transduction mechanism at early stage of severe scald in rats].

Objective: To observe the changes of insulin secretion in the early stage of severe scald in rats, and to explore its signal transduction mechanism. Methods: Twenty-four male Wistar rats aged 7 weeks were divided into sham injury alone (SIA) group, sham injury+ BPV (HOpic) (SIB) group, scald alone (SA) group, and scald+ BPV (HOpic) (SB) group using the random number table, with 6 rats in each group. Full-thickness scald of 50% total body surface area was inflicted in rats of SA and SB groups by a 6-s immersion of the abdomen and a 12-s immersion of the back in 94 ℃ hot water. Rats in SIA and SIB groups received sham injuries through immersion of the back and abdomen in 37 ℃ warm water for 6 and 12 seconds respectively. From 0 (immediately) to 2 day (s) after injury, the rats in groups SB and SIB were intraperitoneally injected with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway enhancer BPV (HOpic) solution (0.5 mg/mL) at the dosage of 0.6 mg/kg once a day, and the rats in groups SA and SIA were intraperitoneally injected with the same volume of dimethyl sulfoxide once a day. At post injury hour (PIH) 72, the tail blood of rats was sampled for measuring fasting blood glucose (FBG) with a glucometer, and the pancreatic tissue samples of rats was harvested for observing the pathological manifestations of islets by hematoxylin-eosin staining, counting the docked granules per 10 µm membrane of islet beta cells and calculating the proportion of insulin vesicles through the observation of the ultrastructure of islet beta cells by transmission electron microscope, and detecting the phosphorylation level of Akt in the pancreatic PI3K/Akt signaling pathway by Western blotting. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: (1) At PIH 72, the rat FBG levels in SIA and SIB groups were normal and similar (P>0.05). Compared with the levels of those two groups, the rat FBG level in SA group was increased significantly (P<0.01), while the level in SB group showed no obvious change (P>0.05). Compared with that in SA group, the rat FBG level in SB group was decreased significantly (P<0.01). (2) At PIH 72, the morphology of rat islets was complete and the islet cells distributed regularly in SIA and SIB groups. Compared with those in SIA and SIB groups, the morphology of rat islets was incomplete, the insulin vesicles in islets were common, the islet cells distributed irregularly, and the cytoplasm of some islet beta cells was lightly stained or translucent in SA group; the morphology of islets in SB group did not change obviously. Compared with those in SA group, the morphology of islets was comparatively complete, the insulin vesicles in islets were less common, the islet cells distributed comparatively regularly, and the lightly stained or translucent cytoplasm of islet beta cells was less in SB group. (3) At PIH 72, the number of docked granules per 10 µm membrane of rat islet beta cells and the proportion of insulin vesicles in SIA and SIB groups were similar (P>0.05). Compared with those in SIA and SIB groups, the number of docked granules per 10 µm membrane of rat islet beta cells in SA group was decreased significantly (P<0.01), while the proportion of insulin vesicles was increased significantly (P<0.01); the number of docked granules per 10 µm membrane of rat islet beta cells in SB group was obviously decreased (P<0.05), while the proportion of insulin vesicles did not change obviously (P>0.05). Compared with those in SA group, the number of docked granules per 10 µm membrane of rat islet beta cells in SB group was significantly increased (P<0.01), while the proportion of insulin vesicles was significantly decreased (P<0.01). (4) At PIH 72, the phosphorylation levels of Akt in SIA, SIB, SA, and SB groups were 0.91±0.03, 0.98±0.03, 0.78±0.08, and 0.87±0.08, respectively. Compared with that in SIA group, the phosphorylation level of Akt was increased obviously in SIB group (P<0.05) but was decreased significantly in SA group (P<0.01), while the level in SB group did not change obviously (P>0.05). Compared with the level in SIB group, the phosphorylation levels of Akt in SA and SB groups were decreased significantly (P<0.01). Compared with that in SA group, the phosphorylation level of Akt in SB group was increased significantly (P<0.05). Conclusions: At the early stage post severe scald in rats, the activity of the pancreatic PI3K/Akt signaling pathway and the function of insulin secretion are reduced. Improving the activity of the pancreatic PI3K/Akt signaling pathway in rats can ameliorate the function of insulin secretion and recover the physiological level of blood glucose.

[Influence of dietary patterns on type 2 diabetes mellitus in local residents aged 40 years and above in Songjiang district, Shanghai].

Objective: To evaluate the association between dietary pattern and type 2 diabetes mellitus (T2DM) in local residents aged 40 years and above in Songjiang district of Shanghai. Methods: Data was obtained from the baseline investigation of Shanghai Peak-Plan cohort. According to inclusion and exclusion criteria, we selected people with T2DM as the case group, and people without T2DM as controls, matched with gender, age and alcohol intake status. Dietary patterns were established by factor analysis. Conditional logistic regression model (CLRM) was used to explore the relationship between different dietary patterns and T2DM, as well as the association between multiplicative interactions of dietary patterns and T2DM. Results: We used factor analysis to obtain six dietary patterns: including meat, desserts-coarse cereals, condiment-egg, beverage, cereals-tubers and fruit-vegetable. Data from multivariate condition logistic regression suggested that condiment-egg patterns as (OR=0.543, 95%CI: 0.377-0.781), beverage (OR=0.590, 95%CI: 0.409-0.852), cereals-tubers (OR=0.592, 95%CI: 0.414-0.848), fruit-vegetable (OR=0.604, 95%CI: 0.417-0.876) were associated with the reduced risks for T2DM. After analyzing the multiplicative interactions between dietary patterns, there were three interaction items associated with T2DM with statistical significances: the multiplicative interaction between meat pattern and condiments-egg pattern was related with the increased risk for T2MD, and the multiplicative interactions between cereal-tubers pattern, meat pattern between cereal-tubers pattern and fruit-vegetable pattern were related with the reduced risks for T2MD. Conclusions: In the six dietary pattern under study, cereals-tubers pattern undwr studly, fruit-vegetable pattern might be more practical in preventing T2DM. In addition, the dietary pattern with cereals and potatos as the main ingredients, appropriate meat and reduced condiment intake might also play positive roles in reducing the risk for T2DM.