Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective To investigate the relationship between stationing years of personnel on an island and their traditional Chinese medicine(TCM)constitution,thus providing a reference for adjusting the health status of stationed personnel,preventing and treating diseases.Methods Based on The Scale of Constitution in Chinese Medicine Questionnaire,TCM constitution of 734 personnel stationed on an island was investigated.Pearson χ2 method was used for data analysis.Results Of the 734 personnel stationed on an island 345(47.0%)were of the balanced constitution type and 389(53.0%)were of the biased constitution types.Among the people with biased constitution types,composite constitution accounted for 80.5%(313 people)and the simple accounted for the rest(19.5%,76 people).The top three types of the biased were dampness heat(15.2%),qi deficiency(14.0%),and yin deficiency(10.7%).The distribution of TCM constitution types was significantly different in terms of stationing years on the island(P<0.05).There was a significant difference in the balanced type and yin deficiency type between people with stationing time≤2 years and>8 years(P<0.05).There was a significant difference in qi deficiency type and qi depression type between people with stationing time≤2 years and>5 years(P<0.05).Compared to people with stationing time≤2 years,significant difference was found in yang deficiency type in people with stationing time ranging from 2 to 5 years and those with>8 years(P<0.05).There were significant differences in the phlegm dampness type,blood stasis type,and specific diathesis type between people with stationing time≤2 years and people with stationing time ranging from>2～5 years and>8 years(P<0.05).There were significant differences in the dampness heat type between people with stationing time≤2 years and people with stationing time ranging from>5～8 years and>8 years,between pepole with stationing time ranging from>2～5 years and people with stationing time>8 years(P<0.05).Conclusion The dampness heat type,qi deficiency type and yin deficiency type are common biased TCM constitution in personnel stationed on islands.The longer the time spent on islands,the greater the possibility of forming biased constitution.

Objective:To preliminarily evaluate the lumen gain of sonodynamic therapy (SDT) mediated by sinoporphyrin sodium at carotid and femoral atherosclerotic plaque sites, and to assess whether concomitant statin use, lesion location, plaque echogenicity/type, and baseline stenosis severity modify the therapeutic response.Methods:This single-center, prospective, exploratory pilot clinical study enrolled patients with peripheral artery disease who attended the outpatient cardiology clinic of the First Affiliated Hospital of Harbin Medical University between February and September 2016. All enrolled patients received optimized oral medical therapy in combination with a single session of SDT. Vascular evaluation was performed using color Doppler ultrasound before treatment and 1 and 4 weeks after treatment. The primary efficacy endpoint was the percent change from baseline in luminal diameter stenosis at the site of the atherosclerotic plaque (%Δ) at week 4, while the secondary efficacy endpoint was %Δ at week 1. Subgroup analyses were conducted according to prior statin use, plaque location, plaque characteristics, and baseline degree of luminal stenosis.Results:A total of 24 patients, aged (70.7±2.2) years were enrolled. There were 20 (83%) males. Compared to baseline, luminal diameter stenosis at the plaque site reduced by week 4 ((50.1±1.2)% vs. (57.2±1.1)%, P<0.001), %Δ was(12.32±1.05)%; and luminal diameter stenosis also reduced by week 1 ((51.7±1.2)% vs. (57.2±1.1)%, P<0.001)), %Δ was(9.61±0.85)%. In subgroup analyses, the treatment effect on diameter stenosis was independent of prior statin use; SDT reduced stenosis in both carotid and femoral plaques; with superior efficacy observed in hypoechoic and mixed-echo plaques; and efficacy was observed across mild, moderate, and severe baseline stenosis categories (all P<0.05). Conclusion:In this single-center pilot study, SDT demonstrates therapeutic efficacy across mild, moderate, and severe stenoses, as well as in hypoechoic and mixed-echo plaques, showing potential to rapidly promote luminal gain at carotid and femoral atherosclerotic plaque sites.

Objective:To preliminarily evaluate the lumen gain of sonodynamic therapy (SDT) mediated by sinoporphyrin sodium at carotid and femoral atherosclerotic plaque sites, and to assess whether concomitant statin use, lesion location, plaque echogenicity/type, and baseline stenosis severity modify the therapeutic response.Methods:This single-center, prospective, exploratory pilot clinical study enrolled patients with peripheral artery disease who attended the outpatient cardiology clinic of the First Affiliated Hospital of Harbin Medical University between February and September 2016. All enrolled patients received optimized oral medical therapy in combination with a single session of SDT. Vascular evaluation was performed using color Doppler ultrasound before treatment and 1 and 4 weeks after treatment. The primary efficacy endpoint was the percent change from baseline in luminal diameter stenosis at the site of the atherosclerotic plaque (%Δ) at week 4, while the secondary efficacy endpoint was %Δ at week 1. Subgroup analyses were conducted according to prior statin use, plaque location, plaque characteristics, and baseline degree of luminal stenosis.Results:A total of 24 patients, aged (70.7±2.2) years were enrolled. There were 20 (83%) males. Compared to baseline, luminal diameter stenosis at the plaque site reduced by week 4 ((50.1±1.2)% vs. (57.2±1.1)%, P<0.001), %Δ was(12.32±1.05)%; and luminal diameter stenosis also reduced by week 1 ((51.7±1.2)% vs. (57.2±1.1)%, P<0.001)), %Δ was(9.61±0.85)%. In subgroup analyses, the treatment effect on diameter stenosis was independent of prior statin use; SDT reduced stenosis in both carotid and femoral plaques; with superior efficacy observed in hypoechoic and mixed-echo plaques; and efficacy was observed across mild, moderate, and severe baseline stenosis categories (all P<0.05). Conclusion:In this single-center pilot study, SDT demonstrates therapeutic efficacy across mild, moderate, and severe stenoses, as well as in hypoechoic and mixed-echo plaques, showing potential to rapidly promote luminal gain at carotid and femoral atherosclerotic plaque sites.

In recent years, exosomes had been recognized as a potential cell-free therapeutic tool in the field of regenerative medicine due to their easy accessibility, low immunogenicity, and good therapeutic effect. As paracrine products of cells, exosomes not only have the functions of their donor cells but also involve fewer ethical disputes. They are more stable than traditional stem cell therapy, and easy to store, transport and sterilize, which are gradually applied in the field of oral regenerative medicine. This article provides a review of the general properties of exosomes and their application in the field of oral regeneration, with a view to exploring new pathways for functional regeneration of the stomatognathic system.

Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.

Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.