With the improvement of China’s scientific research capabilities， the number of innovative drug enterprises and clinical trials has increased， and disputes over damage compensation have also risen accordingly. It has become a consensus to resolve such disputes through institutionalization. Given the similarities between China and India in terms of population and development level， this study analyzed India’s compensation mechanism for clinical trial damage， including the definition of damage， compensation procedures， and calculation methods. Through a comparison of the mechanisms between China and India， this paper put forward suggestions for improving China’s compensation mechanism for clinical trial damage， that is， clarifying the compensation process for clinical trial damage， the scope and calculation methods of damage compensation， and the compensation ratio corresponding to the correlation between damage and clinical trials. It also proposed to use disability weights to measure the participants’ health status before their enrollment in clinical trials， and to calculate the amount of compensation for disability and death based on their health status.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

Objective : To reveal the role of periodontal ligament stem cell-derived exosomes (PDLSC-Exos) in orthodontic bone remodeling, in order to provide new therapeutic strategies for orthodontic tooth movement (OTM). Methods : This study has been reviewed and approved by the Ethics Committee. Healthy periodontal ligament tissues from clinical orthodontic reduction extractions were collected, and periodontal ligament stem cells (PDLSCs) were isolated and cultured. When cultured to the third generation, their self-renewal ability and multidirectional differentiation potential were detected. PDLSC-Exos were isolated and purified by gradient centrifugation and identified by transmission electron microscopy, immunofluorescence, ZetaView, and nanoflow cytometry. The co-culture of 10 μg/mL PDLSC-Exos and PDLSCs (PDLSCs+Exos) induced osteogenic differentiation to evaluate the effect of osteogenesis. Bone marrow-mononuclear cells (BMMs), promoted by osteoclast differentiation [30 ng/mL macrophage colony stimulating factor (M-CSF) + 50 ng/mL receptor activator of nuclear factor-κ B ligand (RANKL)], and then were treated with 10 μg/mL PDLSC-Exos to assess the effect on osteoclasts. We established a rat model of OTM, and 50 μg/mL PDLSC-Exos was injected locally into the periodontal ligament before we established the model (OTM + Exos), every 2 days for 14 days. Alveolar bone remodeling was analyzed by micro-CT, and alveolar bone osteoclasts were analyzed by immunohistochemistry and immunofluorescence. Results: The isolated and purified PDLSCs met the basic characteristics of mesenchymal stem cells, and PDLSC-Exos had typical characteristics of extracellular vesicles. PDLSCs-Exos significantly promoted the osteogenic differentiation of PDLSCs, and promoted the osteoclast differentiation and bone resorption activity of BMMs (P < 0.05). The rate of alveolar bone remodeling in rats with local periodontal injection of PDLSC-Exos was significantly accelerated, and the tooth movement distance was significantly increased (P < 0.05); immunohistochemistry results showed that PDLSC-Exos promoted the differentiation of osteoclasts (P < 0.05). In addition, immunofluorescence showed that PDLSC-Exos co-localized with osteoclasts, indicating that PDLSC-Exos may promote osteoclast differentiation in vivo. Conclusion PDLSC-Exos accelerate the rate of orthodontic bone remodeling by promoting osteogenic differentiation of PDLSCs and osteoclast differentiation of BMMs, thereby accelerating OTM.

AIM: To investigate the correlation of serum Silent mating-type information regulation 2 homolog 1(SIRT1)and Vasostatin-2 content with pathological changes in diabetic retinopathy(DR)patients.METHODS: A total of 104 DR patients(104 eyes)admitted to our hospital from April 2021 to April 2024 were included as the DR group. According to different disease stages, they were assigned into a non-proliferative DR(NPDR)group of 44 cases(44 eyes)and a proliferative DR(PDR)group of 60 cases(60 eyes). Meantime, 104 patients(104 eyes)with simple diabetes were treated as non-DR group. ELISA was applied to detect the levels of SIRT1 and Vasostatin-2 in serum. The diagnostic value of serum SIRT1 and Vasostatin 2 in DR was analyzed by ROC curve. Multivariate Logistic regression was applied to analyze the factors that affected the occurrence of DR. Pearson correlation was applied to analyze the relationship between the levels of SIRT1 and Vasostatin-2 in the serum of DR patients and angiogenesis indicators(VEGF, Ang-2).RESULTS: Compared with the non-DR group, the levels of SIRT1 and Vasostatin-2 in the serum of the DR group were significantly decreased(P<0.05). Compared with the NPDR group, the levels of SIRT1 and Vasostatin-2 in the serum of the PDR group were significantly decreased(P<0.05). Compared with the non-DR group, the levels of VEGF and Ang-2 in the serum of the DR group were obviously higher(P<0.05). Compared with the single detection of serum SIRT1 and Vasostatin-2 levels, combined detection significantly increased the AUC in the diagnosis of DR(Z=4.180, 5.128, all P<0.05). Multivariate Logistic regression analysis showed that HOMA-IR(OR=3.455), fasting blood glucose(OR=1.467), SIRT1(OR=0.836), Vasostatin-2(OR=0.767), VEGF(OR=2.564), and Ang-2(OR=1.834)levels were the influencing factors on the occurrence of DR(all P<0.05). Pearson correlation analysis showed that the levels of SIRT1 and Vasostatin-2 in the serum of DR patients were negatively correlated with VEGF and Ang-2(rSIRT1 vs VEGF=-0.395, rSIRT1 vs Ang-2=-0.474, rVasostatin-2 vs VEGF=-0.323, rVasostatin-2 vs Ang-2=-0.583, all P<0.001).CONCLUSION: The abnormal decrease of serum SIRT1 and Vasostatin 2 levels in DR patients is closely related to the stage of DR lesions and angiogenesis.

To analyze the clinical characteristics of acute diquat poisoning complicated by central nervous system injury (CNSI) and identify early risk factors, aiming to provide a theoretical basis for reducing mortality in diquat poisoning with CNSI.

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

Tophaceous wound represent a severe complication of end-stage gout, characterized by the deposition of monosodium urate (MSU) crystals leading to localized tissue ischemia, chronic inflammation, and non-healing ulcers. The pathological mechanism involves the formation of MSU crystals under persistent hyperuricemia, inflammatory encapsulation, and mechanical compression of the vascular system due to tophus enlarge-ment, ultimately resulting in chronic non-healing ulcers. This article consolidates current evidence to outline an integrated management strategy for such wounds, combining systemic metabolic control with localized interventions. Effective treatment depends on maintaining serum uric acid levels below 300 μmol/L through urate-lowering agents, including conventional drugs and novel urate transporter 1 inhibitors such as AR882, complemented by anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs and glucocorticoids to alleviate pain and reduce inflammation. Topical agents and advanced dressings are utilized to support healing and manage exudate. Debridement, which encompasses sharp, ultrasonic, and micro-techniques, is essential for removing necrotic tissue and MSU deposits, with efficacy assessed via local uric acid monitoring. Surgical reconstructions, including skin flap grafting and tendon or ligament reconstruction, are indicated for significant tissue loss or functional impairment. Long-term management emphasizes continuous metabolic control, personalized rehabilitation, and lifestyle modification. The comprehensive treatment of tophaceous wounds requires multidisciplinary collaboration to balance local repair and systemic regulation for improved prognosis. Future research directions include gene therapy to regulate purine metabolism and artificial intelligence-assisted personalized treatment plans, to achieve precision medicine for tophaceous wounds.
Humans ; Wound Healing ; Gout/therapy* ; Uric Acid/blood* ; Debridement