Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To establish HPLC characteristics of Benincasae Exocarpium from different regions; To simultaneously determine the contents of uridine, guanosine and other nucleosides; To conduct overall evaluation on Benincasae Exocarpium from different regions.Methods:The chromatography was performed on Waters Atlantis ?T3(250 mm×4.6 mm, 5 μm) column with methanol (A) and aqueous solution (B) as mobile phase gradient elution. The detection wavelength was 254 nm, the flow rate was 1.0 ml/min, and the column temperature was 25 ℃. The similarity of common peak of content and characteristic map was used as the main evaluation index to analyze the difference of the Benincasae Exocarpium in different producing areas. Results:15 batches of Benincasae Exocarpium showed 6 common characteristic peaks, and the similarity with the control characteristic maps was greater than 0.90. 5 components of guanine, xanthine, uridine, adenine and guanosine were identified, and uridine and guanosine were quantitatively determined by HPLC. The results showed that, the contents of uridine and guanyl in 15 batches of Benincasae Exocarpium ranged from 0.017% to 0.036% and 0.018% to 0.031%. The highest content of uridine was 0.036% in Jiaozuo City of Henan Province, and 0.031% in Changde City of Hunan Province.Conclusions:This HPLC method has good precision, repeatability and stability, and the two components of uridine and guanosine have good linear relationship in the determination range, which can objectively and comprehensively evaluate the overall appearance of Benincasae Exocarpium from different regions. The difference of nucleoside efficacy components of Benincasae Exocarpium from different regions is small.

Objective:To investigate the risk factors of olfactory dysfunction (OD) of female patients with primary Sj?gren′s syndrome (pSS) and a prediction model was constructed.Methods:A total of 252 female pSS patients in the Third Municipal Hospital of Huzhou, from January 2021 to 2023 were recruited. According to the olfactory function,they were divided into OD group (144 cases) and without OD group (108 cases).The independent risk factors of OD were evaluated and the clinical prediction efficiency of the model was analyzed by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and the decision curve analysis (DCA) curve.Results:The rate of OD was 57.1%((144/252)) in female pSS patients. Hyposmia was the main olfactory disorder in OD group (140/144, 97.2%). Univariate analysis showed that there were significant differences between OD and without OD groups, including disease course ( t=-2.05, P=0.040), RF( t=2.90, P=0.004), IgG( t=4.41, P=0.001), C3( t=5.47, P=0.001), ESSPRI( t=2.55, P=0.011), ESSDAI( t=3.80, P=0.001), HAMD ( t=3.38, P=0.001). Logistic regression analysis showed that high serum RF, IgG and low complement 3, high scores of ESSDAI and HAMD high scores were independent risk factors for pSS patients with OD patients[ OR(95% CI)=1.01(1.01, 1.03), 1.21(1.06, 1.38), 0.98(0.96, 0.89), 1.52 (1.20, 1.92), 1.13(1.03, 1.23)] ( P value were 0.016, 0.005, 0.004, <0.001 and 0.007 respectively). Based on the above independent risk factors, we constructed the prediction model nomogram and performed the internal data validation. The ROC curve AUC (95% CI) of the modeling group was 0.83(0.77, 0.89) and validation group was 0.69(0.57, 0.82), the prediction model was well differentiated.Hosmer-Lemeshow goodness-of-fit test showed that the prediction model had good calibration ability ( P=0.083), and the DCA curve display model is clinically valuable. Conclusion:The clinical prediction model developed in this study can be used to assess the risk of pSS-OD development, which is helpful for early detection and timely interention so can improve the quality of life of pSS-OD patients in turn.

Black phosphorus, as a novel two-dimensional nanomaterial, has received a lot of attention from researchers for its unique structure and properties. In recent years, with the increasing cross-sectional research related to black phosphorus 2D nanomaterials in various fields such as materials science, physics, chemistry, biology, and medicine, it has shown great potential for development and application in biomedicine. The excellent photoacoustic properties and good biocompatibility of black phosphorus 2D nanomaterials make them outstanding in tumor diagnosis and treatment. In this paper, the structure and properties, preparation, and functional modification of black phosphorus two-dimensional nanomaterials and their potential applications in the bio-detection and treatment of tumors, as well as the application progress of antibacterial were reviewed.

Objective: To understand health literacy and its associated factors among middle school students in Shenzhen, to provide scientific basis for further formulating targeted intervention measures. Methods: From October to December, 2019, 7 423 middle school students in 10 districts of Shenzhen were selected by multistage stratified random cluster sampling. Multivariate linear regression was used to analyze factors affecting health literacy and scores in each dimensions. Results: The total score for health literacy was(107.39±22.31), including physical activity(16.81±5.28), interpersonal relationship(20.69±4.10), stress management(21.64±5.53), spiritual growth(14.93±3.96), health awareness (15.61±4.96) and nutrition(17.71±4.65). According to the multivariate linear regression analysis, girls, general and vocational high schools, educational level of parents and boarding in school were significantly associated with health literacy of middle school students( B=-3.04, -7.72, -9.99, 1.56, 2.78, -3.85, P < 0.05 ). Conclusion Middle school students in Shenzhen have a high level of health literacy, which is related to school type and parental educational background. It is suggested that measures should be taken to improve the health literacy of middle school students.

Objective    To quest the risk factors of poor prognoses in children with tetralogy of Fallot (TOF) during perioperative period and evaluate its clinical application values. Methods    A retrospective analysis of the clinical data of 119 children who underwent one-stage correction of TOF in Guangdong Provincial People's Hospital from September 2016 to January 2019. The cohort includes 75 males and 44 females, with ages ranging from 3.2-137.1 (13.2±1.4) months and weights ranging from 4.6-21.0 (8.3±0.2) kg. Perioperative poor prognosis was defined as duration of mechanically assisted ventilation >48 h or secondary intubation, vasoactive-inotropic score (VIS) within 48 h >40, postoperative length of stay >14 d, and the occurrence of the major adverse events. Major adverse events were defined as early death, malignant arrhythmia, low cardiac output syndrome, non-fatal cardiac arrest, postoperative reintervention, diaphragm paralysis, and other clinical complications. Univariate and multivariate logistic analyses were used to analyze the correlation between risk factors and poor prognoses. Results    There was 1 perioperative death, and 9 with major adverse events. Variables selected by Least Absolute Shrinkage and Selection Operator (LASSO) included 2 preoperative variables (McGoon index, aortic root diameter index) and 4 intra-operative variables [left-right direction of bicuspid pulmonary valve, total length of right ventricular outflow tract (RVOT) incision index, pulmonary valve with commissurotomy, and minimum temperature in cardiopulmonary bypass (CPB)]. Univariate and multivariate logistic analyses were used to the above factors, respectively. The variables with statistical significance (P≤0.05) were McGoon index, aortic root diameter index, left-right direction of bicuspid pulmonary valve, and minimum temperature in CPB. A nomogram was established based on the above factors, and the results showed that the left-right direction of bicuspid pulmonary valve was more risky than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. The lower the McGoon index, the higher aortic root diameter, and the lower temperature in CPB, the higher risk of poor prognostic events in children with TOF. Conclusion    The left-right direction of the pulmonary bicuspid valve has a higher risk of poor prognosis than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. With the smaller McGoon index and the larger aortic root diameter, the risk of poor prognoses in children with TOF is higher. The temperature in CPB being lower than medium-low temperature obviously relates to the high incidence of poor prognostic events, which can be used as an auxiliary reference standard for decision-making in pediatric TOF surgery in the future.

Objective To study the relationship among bile components and different gallstone types through comparing and analyzing gallbladder bile contents in patients with different types of gallstones.Methods A retrospective study of 542 consecutive patients with gallstones or gallbladder polyps was conducted.The stone composition type and 14 kinds of bile components from these patients were analyzed.The bile parameters consisted of potassium (K +),sodium (Na+),chlorine (Cl-),calcium (Ca2+),bicarbonate (HCO3-),magnesium (Mg2+),aspartate aminotransferase (AST),glutamyltranspeptidase (GGT),alkaline phosphatase (ALP),total bilirubin (TBIL),total bile acid (TBA),cholesterol (CHO),lactate dehydrogenase (LDH) and pH.Finally,the content of these bile components among the different types of stones and gallbladder polyps were compared.According to the composition determined by Fourier transform infrared spectroscopy (FTIR),the gallstone patients were divided into five groups.Results Compared with other groups,the content of K +,GGT,ALP,TBIL,TBA and CHO in the calcium carbonate stone group were lower (P ＜ 0.05),while the levels of C1-,HCO3-and value of PH were higher (P ＜0.05).Furthermore,CHO content in the cholesterol stone group was higher than other groups (P ＜ 0.05)except for the gallbladder polyp group (P ＞ 0.05).In addition,there was no difference in bile contents among the pigment gallstone group,mixed stone group and polyp group (P ＞ 0.05).Conclusions In gallstone patients,the bile components of patients with calcium carbonate stones is significantly different.The high cholesterol content in bile is the main feature of cholesterol stone patients,and there is no significant difference in bile composition between patients with pigment stones and mixed stones.

Objective To investigate if the ratio of pulmonary valve annulus, which is the proportion of pulmonary valvular annulus size to total size of aortic valvular annulus and pulmonary valvular annulus, can better guide the choice of surgical approach than the value of z. Methods A retrospective analysis was made for 254 patients who underwent total correction of tetralogy of Fallot in Guangdong General Hospital between January 2016 and January 2018. There were 154 males and 100 females with an average age of 14.60±18.76 years. The patients were categorized into two groups, a transannular patch group (TAP, n=164) and a non-TAP group (n=90). The sizes of pulmonary and aortic valvular annulus were evaluated in each group, and the cutoff value of proportion of pulmonary valvular annulus for TAP was calculated. Results Both proportion of pulmonary valvular annulus and z-scores were smaller in the TAP group than those in the non-TAP group (0.29±0.06 vs. 0.36±0.06, P<0.001; –4.04±2.13 vs. –2.06±1.84, P<0.001, respectively). In receiver operating characteristics analyses, proportion of pulmonary valvular annulus and the z-score cutoff values were 0.353 (area under the curve 0.781, 95%CI 0.725–0.831) and –2.13 (area under the curve 0.766, 95%CI 0.709–0.817), respectively, demonstrating that the proportion of pulmonary valvular annulus was a more powerful diagnostic tool as a predictor of TAP. Conclusion Our results suggest that the proportion of pulmonary valvular annulus is an effective predictor for TAP and can be easily applied to clinical practice.

Objective To summarize the diagnosis and surgical treatment of mesenteric cyst in children.Methods The clinical records of mesenteric cyst cases from January 2011 to December 2015 were reviewed retrospectively.The diagnosis and treatment options were analyzed, and the prognosis of laparoscopic surgery and laparotomy was compared.Results The main clinical symptoms included abdominal mass, abdominal pain, and abdominal distension.Abdominal ultrasound and/or CT scan were the diagnostic tools in all cases.Traditional laparotomy was performed in 14 cases, while laparoscopy in 7 cases (1 case switched to laparotomy).2 cases had emergency surgery due to acute abdomen, laparotomy and laparoscopy in each case.Simple cyst resections were completed in 14 cases, of which 2 cases with a small amount of residual in the mesenteric root.Intestinal resection and anastomosis were required in other 7 cases.The average time of hospital stay for laparotomy group was 12 days, and 10.14 days for laparoscopy group.There was no significant difference.All patients were discharged without postoperative complications.With 1-4 years follow-up, there was no recurrence.Conclusion The operation for mesenteric cysts depends on the relationship between the cyst and the adjacent bowel or organs, and the overall outcome is favorable.The selective use of laparoscopy will benefit more children.