Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective:To investigate the mortality-related factors affecting patients with gastrointestinal perforation who are transferred to the intensive care unit (ICU) and to establish a prediction model, and to evaluate the predictive performance of the model.Methods:A retrospective analysis was performed on the medical records of 306 patients who underwent gastrointestinal perforation surgery in Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2021 to January 2024 and were transferred to intensive care unit after surgery, including 176 males and 130 females, aged from 28 to 92 years with the average of (66.07±16.03) years. According to the prognosis, patients were divided into survival group ( n=264) and death group ( n=42). Clinical characteristics of the two groups were compared, univariate and multivariate Logistic regression was used to analyze the risk factors of perioperative death, and the related risk factors were selected to establish a nomogram prediction model, the subject work curve was drawn, and the area under the curve (AUC) was calculated. Evaluate its predictive effectiveness; The calibration chart and clinical decision curve were further used to evaluate the prediction accuracy and clinical application value of the model. Results:Clinical data analysis showed that age, white blood cell count, procalcitonin, lactic acid level, preoperative shock, preoperative underlying diseases (cerebral infarction, hormone history), intraoperative blood loss, postoperative lung infection in the death group were higher than those in the survival group ( P<0.05), and hemoglobin was lower than those in the survival group ( P<0.05). Multivariate Logistic regression analysis showed age ( OR=1.422, 95% CI: 1.205-1.680, P<0.001), hemoglobin ( OR=0.945, 95% CI: 0.904-0.987, P=0.012), white blood cell count ( OR=1.832, 95% CI: 1.341-2.501, P<0.001), procalcitonin ( OR=1.099, 95% CI: 1.012-1.192, P=0.024), lactic acid level ( OR=16.435, 95% CI: 3.729-72.425, P<0.001), reoperative shock ( OR=172.358, 95% CI: 13.059-2274.773, P<0.001), intraoperative blood loss ( OR=1.041, 95% CI: 1.017-1.065, P=0.001) and postoperative pulmonary infection ( OR=38.670, 95% CI: 3.449-433.553, P=0.003) was an independent risk factor for perioperative death in intensive care patients after DTP. Based on the screened independent risk factors ( P<0.05), a nomogram model was established and receiver operating characteristic (ROC) curve was drawn. The model area under the curve was 0.985. The accurate graph shows that the predicted results of the model are in good agreement with the actual clinical results, and the analysis of clinical decision curve indicates that the model has high clinical prediction value. Conclusion:Age>71.5 years, hemoglobin< 109 g/L, white blood cell count>17.9×10 9/L, procalcitonin>6.225 ng/mL, lactate level>2.25 mmol/L, preoperative shock, intraoperative blood loss>45 mL and postoperative pulmonary infection are independent risk factors for perioperative death in intensive care patients after DTP.

Objective:To learn about the clinical manifestations, laboratory characteristics and treatment of patients with acute and chronic brucellosis.Methods:Clinical data of 153 brucellosis patients admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from 2012 to 2022 were retrospectively collected, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, imaging examination results, treatment and prognosis. According to the course of disease < 180 d and ≥180 d, these patients were divided into acute brucellosis group and chronic brucellosis group, and the clinical data of the two groups of patients were compared and analyzed.Results:A total of 153 patients with brucellosis were included, including 119 in the acute brucellosis group and 34 in the chronic brucellosis group. The age was (46.2 ± 13.8) years old, with 115 males (75.2%) and 38 females (24.8%), and 85 patients (55.6%) were occupational exposed. Complications occurred in 90 patients (58.8%), and the incidence of complications in the acute brucellosis group was lower than that in the chronic brucellosis group [76.5% (26/34) vs 53.8% (64/119), χ 2 = 5.62, P = 0.018]. The most common clinical manifestations were fever and arthralgia, with 128 cases (83.7%) and 124 cases (81.0%), respectively. The incidence of fever in the acute brucellosis group was higher than that in the chronic brucellosis group [87.4% (104/119) vs 70.6% (24/34), χ 2 = 5.46, P = 0.019], while the incidence of arthralgia was lower than that in the chronic brucellosis group [77.3% (92/119) vs 94.1% (32/34), χ 2 = 4.83, P = 0.027]. In laboratory tests, the positive rate of blood culture was 59.5% (91/153), and it was higher in the acute brucellosis group than that in the chronic brucellosis group [67.2% (80/119) vs 32.4% (11/34), P < 0.05]. The incidence of elevated procalcitonin [PCT, 58.6% (58/99) vs 24.1% (7/29), χ 2 = 10.65, P = 0.001] and the incidence of liver dysfunction [33.9% (40/118) vs 15.2% (5/33), χ 2 = 4.33, P = 0.037] in the acute brucellosis group were higher than those in the chronic brucellosis group. In the imaging examination, 61 patients (39.9%) experienced bone destruction, and the incidence of bone destruction in the chronic brucellosis group was higher than that in the acute brucellosis group [55.9% (19/34) vs 35.3% (42/119), χ 2 = 4.68, P = 0.031]. All patients were treated with antibiotics, with a median of 3 and 4 types of antibiotics used in the acute and chronic brucellosis groups, respectively. The overall incidence of adverse drug reactions was 5.2% (8/153). After treatment, 65 cases (42.5%) recovered, 70 cases (45.8%) improved, and 18 cases (11.8%) did not recover. Conclusions:The main clinical manifestations of brucellosis patients are fever and arthralgia, with a high incidence of complications. All patients are treated with combined antibiotics therapy. Patients in acute brucellosis group have a higher incidence of fever, positive blood culture, elevated PCT and abnormal liver function, while patients in chronic brucellosis group have a higher incidence of complications, arthralgia and bone destruction.

The accurate deduction of postmortem interval is a difficult and extremely critical task in the field of forensic pathology and criminal investigation.In recent years,physics,chemistry,microbiology,immunology,entomology,molecular biology and other disciplines have been on the rise,and special staining,spectroscopy,mass spectrometry,chromatography,radiographic and other techniques have been developed,and methods for postmortem interval inference are increasing,among which immunolabelling techniques have played an important role.In this paper,we systematically reviewed the domestic and foreign relevant studies on the postmortem interval inference using of immunolabelling techniques,including immunohistochemistry,immunoblotting,immunofluorescence,radioimmunoassay,etc.We summarized and analyzed the research progress on these techniques in postmortem interval inference,with the aim of exploring the ideas for the study of postmortem interval inference in forensic pathology,and provide reference for better applying them in forensic practice.

Given that the existing methods of enhancing the resolution of magnetic resonance(MR)images by algorithms mainly focus on cross-size and same-size supervised super-resolution algorithms,a super-resolution reconstruction network(SG-Diffusion)for MR images is proposed based on an implicit degradation mapping model.The degradation process of MR images is implicitly modeled through a masked autoencoder,which reduces the domain gap between the experimental constructed dataset and the actual MR images,and the sample pairs are generated based on implicit degradation model.After training,a MR image reconstruction network based on self-guided diffusion model is obtained to realize the spatial resolution enhancement of unsupervised same-size MR images.The results of super-resolution experiments of 4-fold accelerated sampling brain MR images on fastMRI dataset show that the MR image super-resolution reconstruction network based on implicit degradation model proposed in the study can effectively improve the spatial resolution of degraded MR images,and that compared with the image degradation reconstruction method based on the explicit degradation model,the proposed SG-Diffusion method achieves better reconstruction results.

Objective To explore the effect and related mechanism of Zuogui Jiangtang Jieyu Prescription on neuroinflammation of nucleus accumbens in rats with diabetes mellitus(DM)complicated with depression based on dopamine receptor.Methods DM,depression and DM complicated with depression models were respectively established through a combination of high-fat feeding and streptozotocin intraperitoneal injection,as well as chronic unpredictable mild stress+solitary cage feeding.The rats were divided into control group,depression group,DM group,DM complicated with depression group,positive group,D1R agonists group,D2/3R agonists group and Zuogui Jiangtang Jieyu Prescription group.Depression and learning and memory abilities in rats were assessed using open field experiments,forced swimming experiments and water maze experiments.Neuronal damage in nucleus accumbens was detected through HE and Nissl staining.Serum contents of 5-hydroxytryptamine(5-HT),dopamine(DA),interleukin(IL)-1β and IL-18 were detected by ELISA.The expressions of D1R,D2R,D3R and Iba1/NLRP3 in nucleus accumbens were detected by immunofluorescence.The protein expressions of D1R,D2R,D3R,NLRP3,ASC,Caspase-1 p20 and IL-1β in nucleus accumbens were detected by Western blot.Results Compared with the control group,the changes of fasting blood glucose(FBG)in rats of DM complicated with depression group significantly increased(P<0.01),the total distance and number of activities in the open field experiment,the time ratio of staying in the original platform quadrant and the number of times crossed the original platform in the water maze experiment significantly decreased(P<0.05,P<0.01),the forced swimming immobility time and the escape latency period in the water maze experiment were prolonged(P<0.05,P<0.01),the contents of serum 5-HT and DA significantly decreased(P<0.01),the contents of IL-1β and IL-18 significantly increased(P<0.05,P<0.01),neurons in the nucleus accumbens showed nuclear condensation,degeneration,and increased necrotic cells,with loss of Nissl bodies,the expressions of D1R,D2R and D3R were significantly decreased(P<0.01),while the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein significantly increased(P<0.05,P<0.01).Compared with the DM complicated with depression group,the changes of FBG significantly decreased in the Zuogui Jiangtang Jieyu Prescription group,learning and memory abilities were enhanced,depression-like behavior was improved,and the damage to neurons in the nucleus accumbens was reduced,the contents of serum 5-HT and DA significantly increased(P<0.01),the contents of IL-1β and IL-18 significantly decreased(P<0.01),the expressions of D1R,D2R and D3R in the nucleus accumbens increased(P<0.05,P<0.01),and the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein decreased(P<0.05,P<0.01).Conclusion The dopaminergic system dysfunction and neuroinflammation are the key mechanisms of DM complicated with depression.Zuogui Jiangtang Jieyu Prescription may improve neuroinflammation by regulating the dopamine receptor to inhibit the activation of microglial NLRP3 signaling in the nucleus accumbens.

Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ²=18.89, P<0.05). The incidence rate of the 60-74 years old group was 3.38/100,000, and the total number of cases in the age group 45-74 years was 416 (74.95%). Occupational distribution was mainly among farmers, with 448 cases (80.72%). The top three regions with the highest number of reported cases (in order: Donghai County, Ganyu District, and Guannan County) reported a total of 416 cases, accounting for 74.95%. Concentration ratio was M=0.9408, and the incidence of scrub typhus disease was strictly seasonal. Circular distribution results showed a^-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.

Objective To investigate the significance of intratumoral and peritumoral radiomics models in predicting occult lymph node metastasis in stage T1 non-small cell lung cancer(NSCLC)and to compare the predictive accuracy in different peritumoral radiomics models.Methods The CT images and clinical data of 211 patients without lymph node metastasis on preoperative CT examination and pathologically confirmed NSCLC after surgery were collected.The radiomics features were derived from the three-dimensional volume of interest(VOI)of the intratumoral and peritumoral at 3-,5-,and 10-mm following lesion segmentation on CT images of each patient.The feature data of all nidus were radomly divide into training set and validation set with a ratio of 7︰3.The Pearson or Spearman correlation test was performed to remove redundancy.Dimensionality was reduced by the least absolute shrinkage and selection operator(LASSO)regression analysis.The linear combination of selected features and corresponding coefficients were used to construct the Radiomics score(Radscore).The clinical model and comprehensive model were constructed by logistic regression analysis.The conprehensive model was visualized with the nomogram,and its performance was evaluated.Results Among the peritumoral radiomics models,the peritumoral 5-mm model showed the best predictive efficacy[validation set,area under the curve(AUC)0.771].The comprehensive model containing Radscore,CT image features and CEA exhibited the best performance(validation set,AUC 0.850).Conclusion Intratumoral and peritumoral radiomics models perform efficiently in predicting occult lymph node metastasis in stage T1 NSCLC,and nomogram can effectively and noninvasively predict occult lymph node metastasis in NSCLC.