Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Non-classical congenital adrenal hyperplasia (NCCAH), an autosomal recessive disorder, stems from genetic mutations affecting the enzymes and cofactors integral to adrenal steroidogenesis. These mutations may result in diminished activity or a complete loss of function for critical enzymes, such as 21-hydroxylase, 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and the steroidogenic acute regulatory protein (StAR). The impairment of these enzymatic processes has profound implications for reproductive health in females, mediated through both genetic and endocrine pathways. This review aims to explore the pathogenesis of various enzyme defects in different types of NCCAH, their clinical features, and their impact on female fertility. It is hoped that this will help refine the diagnostic strategies for infertility associated with NCCAH, thereby enhancing fertility of patients and providing new directions and opportunities for further research in this field.

Non-classical congenital adrenal hyperplasia (NCCAH), an autosomal recessive disorder, stems from genetic mutations affecting the enzymes and cofactors integral to adrenal steroidogenesis. These mutations may result in diminished activity or a complete loss of function for critical enzymes, such as 21-hydroxylase, 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and the steroidogenic acute regulatory protein (StAR). The impairment of these enzymatic processes has profound implications for reproductive health in females, mediated through both genetic and endocrine pathways. This review aims to explore the pathogenesis of various enzyme defects in different types of NCCAH, their clinical features, and their impact on female fertility. It is hoped that this will help refine the diagnostic strategies for infertility associated with NCCAH, thereby enhancing fertility of patients and providing new directions and opportunities for further research in this field.

Objective:To explore the status quo of pediatric nurses' cognition of death education, and analyze its influencing factors, so as to provide experience and reference for carrying out death education in pediatric wards.Methods:In this study, 827 nurses from 15 children's hospitals in China were investigated by using the scale for evaluating the cognition of death education in medical staff prepared by Zhang Yan-gai, and the related factors affecting the cognition of death education were analyzed. SPSS 23.0 was used for independent-samples t-test and ANOVA analysis, and multiple regression equation was used to further analyze the relationship between the cognitive factors of death education in pediatric nurses. Results:The total score of death education cognition of pediatric nurses was (35.61±5.64) points, which was lower than the median score of 36 points. The degree of death education cognition of pediatric nurses was at the medium-low level. The results of correlation analysis showed that the professional title of nurses (regression coefficient: 0.064, P=0.045), the training demand for death education (regression coefficient: 0.300, P<0.001), and the way of understanding (regression coefficient: 0.018, P=0.003) were independent influencing factors of the death education cognition level of pediatric nurses. Conclusions:Pediatric nurse death education related theoretical knowledge should be improved through various professional trainings. The hospitals should include death education in pediatric nurse continuing education training plan to improve pediatric nurses' cognitive level of death education through a variety of ways and means, promote the application of death education activities carried out in pediatric ward in the hospice care, reduce deaths impact to nurse their own emotions, and alleviate parents' anxiety and painful experience, thereby improving medical satisfaction.

Jasmonic acid (JA), a plant endogenously synthesized lipid hormone, plays an important role in response to stress. This manuscript summarized the biosynthesis and metabolism of JA and its related regulatory mechanisms, as well as the signal transduction of JA. The mechanism and regulatory network of JA in plant response to biotic and abiotic stresses were systematically reviewed, with the latest advances highlighted. In addition, this review summarized the signal crosstalk between JA and other hormones in regulating plant resistance to various stresses. Finally, the problems to be solved in the study of plant stress resistance mediated by JA were discussed, and the application of new molecular biological technologies in regulating JA signaling to enhance crop resistance was prospected, with the aim to facilitate future research and application of plant stress resistance.
Signal Transduction ; Cyclopentanes ; Oxylipins ; Plant Growth Regulators

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Objective To enhance the triage efficiency of patients with acute heart failure(AHF)by improving emergency severity index(ESI)score,and to achieve stratified care for patients with AHF.Additionally,the aim is to improve the combination of stratified scores and nursing care in emergency departments to address the limitations of current studies.Methods A retrospective nested cohort study was conducted on 120 patients with AHF admitted to the Affiliated Hospital of Guizhou Medical University from January 1,2019 to December 30,2021.According to the clinical outcomes of the patients,the patients were divided into subgroup A(71 cases,recovered after treatment,no serious complications during treatment),subgroup B[35 cases,discharged after treatment,multiple organ dysfunction syndrome(MODS),acute respiratory distress syndrome(ARDS),shock and other serious complications occurred during treatment],and subgroup C(14 cases,cardiac death during treatment).A prospective randomized controlled study involving 106 patients with AHF admitted to our hospital from January 1 to December 30,2022,was conducted,and the patients were divided into control group(53 cases)and stratified care group(53 cases)according to the random number table method.The control group received routine nursing care,while patients in the stratified care group received stratified care based on the ESI scoring clinical care pathway.The early warning score model of elderly patients with AHF was constructed with risk threshold as warning signal.The improved ESI scoring criteria were used to score AHF patients,with a total score of 25 points.The higher the score,the higher the risk.0-10 is divided into Ⅰ level risk,>10-20 is divided into Ⅱ level risk,>20 is divided into Ⅲ level risk.Implement nuring at grades Ⅲ,Ⅱ,and Ⅰ,respectively.The changes of modified ESI scores in subgroup A,subgroup B and subgroup C were observed,and Spearman correlation coefficient was used to evaluate the correlation between modified ESI scores and clinical outcomes of different severity of disease.Receiver operator characteristic curve(ROC curve)was drawn to evaluate the effectiveness of the risk threshold classification method of different nursing plan designs in the stratified nursing group and the control group,and to compare the efficiency differences of emergency nursing rescue time,rescue success rate,and stay time in the emergency department,and the incidence of complications such as MODS,ARDS,shock and nursing satisfaction during treatment between the stratified nursing group and the control group.Results The modified ESI score in subgroup C was the highest,significantly higher than that in subgroup B and A(19.6±1.7 vs.17.8±1.5,15.3±1.3,all P<0.05).Spearman correlation analysis showed that the modified ESI score was significantly positively correlated with the occurrence of complications,the occurrence of cardiac death,and the recovery after treatment(r values were 0.623,0.635,0.322,P values were 0.004,0.003,0.012,respectively).Therefore,an improved ESI score has a certain early warning effect on complications and cardiac death of patients.ROC curve analysis showed that the area under the ROC curve(AUC)of routine care for stratified care was 0.710 and 0.620,and the 95％ confidence interval(95％ CI)was 0.620-0.750 and 0.580-0.690,respectively,with Pvalues of 0.023 and 0.034.It shows that the difference between the two nursing methods is significant,and further indicates that the risk threshold classification method designed in this study is effective.With the increase of risk,the rescue time and emergency stay time of the two groups were gradually extended,and the success rate of rescue was gradually decreased,the rescue time and emergency stay time of grade Ⅲ risk were the longest and the success rate of rescue was the lowest,and the rescue time and emergency stay time of the stratified nursing group were significantly shorter than those of the control group(minutes:59.6±6.3 vs.76.5±7.2 and 57.6±5.4 vs.68.2±7.1,both P<0.05),the success rate of rescue was significantly increased[(68.7±6.1)％ vs.(54.6±5.2)％,P<0.05],and the difference of rescue time between grade Ⅰ risk and grade Ⅲ risk was the largest.There were significant differences in the success rate of rescue and the duration of emergency stay in grade Ⅲ risk.The incidence of complications such as MODS,ARDS and shock in stratified care group was significantly lower than that in control group[incidence of MODS:13.2％(7/53)vs.18.9％(10/53),incidence of ARDS:15.1％(8/53)vs.22.6％(12/53),incidence of shock:13.2％(7/53)vs.20.8％(11/53),all P<0.05],satisfaction of patients with service attitude,operation technique,comfort and timeliness were significantly improved compared with the control group[service attitude:28.3％(15/53)vs.18.9％(10/53),operation technology:30.2％(16/53)vs.20.8％(11/53),comfort:32.1％(17/53)vs.24.5％(13/53),timeliness:32.1％(17/53)vs.24.5％(13/53),all P<0.05].Conclusion Based on the modified ESI score,early risk warning thresholds are divided and stratified nursing is conducted,which is beneficial for timely intervention in AHF,effectively ensuring the clinical nursing value of patients during the implementation of medical measures,and has broad application prospects.

Objective:To investigate the incidence of alopecia after pediatric liver transplantation and its related risk factors.Methods:A retrospective case-control study was used. The subjects were children who underwent liver transplantation in the Second Affiliated Hospital, Zhejiang University School of Medicine from July 2019 to December 2020. The information such as gender, age, primary disease, preoperative body mass index (BMI), graft-to-recipient weight ratio (GRWR), albumin, hemoglobin and total bilirubin before the operation, and blood concentration of tacrolimus were collected from the hospital information system. The follow-up content included whether there was alopecia after surgery, the site of alopecia, the degree of alopecia, the occurrence time and recovery time of alopecia after surgery. The children were divided into alopecia group and non-alopecia group according to whether there were alopecia, and the related indicators were analyzed by univariate analysis, and the results were expressed by odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 40 children who met the inclusion criteria were collected, including 20 males and 20 females. The median age at surgery was 20(11, 43) months and the age ranged from 5 months to 13 years. The BMI was (17.1±2.1) kg/m 2 and the GRWR was (2.6±0.7)%. The serum TBil, blood albumin, and hemoglobin before the operation were 120 (27, 191) μmol/L, (33±5) g/L, and (100±14) g/L, respectively. The blood concentration of tacrolimus was (10.37±2.15) μg/L within one month after the operation. Among the 40 children, 17 developed alopecia, including 8 males and 9 females. The severity of alopecia was S 1 in 16 cases and S 2 in 1 case. There were 14 cases of local hair loss and 3 cases of general hair loss. The occurrence time of alopecia in all 17 patients was distributed from 4 days to 9 months after operation, including 15 cases within 1 month after operation, and 2 cases 3 and 9 months after operation, respctively. All patients did not receive symptomatic treatment for alopecia and returned to normal within 1 year after the operation. Univariate analysis showed that low preoperative albumin level and high concentration of tacrolimus within one month after surgery were risk factors for alopecia after pediatric liver transplantation [ (31±4) g/L vs. (34±5) g/L, OR=0.83, 95% CI: 0.71-0.98, P=0.026; (12.0±2.1) μg/L vs. (9.2± 1.2) μg/L, OR=2.80, 95% CI: 1.55-5.05, P=0.001]. Conclusion:Low preoperative albumin level and high concentration of tacrolimus within one month after surgery may be risk factors for alopecia in children after liver transplantation.