Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To integrate tumor proliferation and immune-related biomarkers to construct a nomogram prediction model for predicting the prognosis of ovarian cancer patients.Methods We collected clinical information from patients diagnosed with epithelial ovarian cancer(EOC)between 2009 and 2013.Immunohistochemical staining was performed to detect the expression levels of KI67,epidermal growth factor receptor(EGFR)and programmed death-ligand 1(PD-Ll)in tumor tissues.We employed Lasso-Cox regression to identify variables and construct the nomogram model.We used time-dependent receiver operating characteristic(ROC)curves,concordance index,calibration curves,and decision curve analysis(DC A)curves to assess the model's discrimination,calibration,and net clinical benefit ability,respectively.Additionally,we conducted Kaplan-Meier survival analysis to assess the prognostic value of the model's risk score.Results We included a total of 131 EOC patients who were randomly assigned to the training set(n=79)and validation set(n=52)in a 6∶4 ratio.Lasso-Cox regression identified seven variables for constructing the nomogram prediction model.The AUCs for 1-,4-,and 6-year overall survival in the training set were 0.911,0.943,and 0.968,respectively,with a consistency index of 0.86[95％confidence interval(CI):0.81-0.91].In the validation set,the AUCs for 1-,4-,and 6-year overall survival were 0.830,0.797,and 0.828,respectively,with a consistency index of 0.71(95％CI:0.64-0.78).The calibration curves in both training and validation sets demonstrated strong agreement between model-predicted survival and actual outcomes(all P＞0.05).DCA curves indicated that the modeled net clinical benefit outperformed TNM staging.Patients with high-risk scores in the model exhibit poorer overall survival(P＜0.01)and progression-free survival(P＜0.01).Conclusion The successful development and validation of a nomogram prediction model based on tumor proliferation and immune-related biomarkers offer an efficient and straightforward clinical tool.This tool holds promise for enabling personalized treatment strategies for patients with ovarian cancer.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

Objective:To explore the application of biomechanics principle in the repair of double eyelid disappearance after blepharoplasty.Methods:A retrospective analysis was performed on 47 patients (46 females and 1 male) with double eyelid disappearance after blepharoplasty in the Department of Plastic and Cosmetic Surgery, Friendship Plastic Surgical Hospital from July 2018 to December 2022. The patients aged from 19-42 (28±8) years. The repair surgery was performed by increasing the mechanical factors that promoted the double eyelid formation or weakening the mechanical factors that inhibited the double eyelid formation. The overall satisfaction with ocular appearance, and psychological well-being and social function were evaluated with the Face-Q qustionnaires before or after operation.Results:By following-up for 3-24 months, the morphology of upper eyelids in all 47 patients were remarkably improved. 2 patients complained about asymmetry and 1 patient had multiple creases, for whom satisfactory results achieved after re-operation. The remaining patients presented smooth natural double eyelid line, and concave groove deformity when eyes closed were not noticed. The operative effects were satisfactory. After surgery, the scores for ocular satisfaction with facial appearance, psychological well-being and social function were (69.5±10.3), (75.5±13.6) and (68.3±11.3) scores, which were significantly increased than those before operation [(38.7±9.3), (54.8±10.5) and (52.3±8.7) scores], respectively (all P<0.05). Conclusion:More effective and reliable operation results can be obtained in the repair strategies of double eyelid disappearance after blepharoplasty by utilizing the biomechanical mechanism.

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*