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

In this paper， we systematically sorted out and verified the name， origin， producing area change， quality， efficacy and processing of Halloysitum Rubrum by consulting materia medica， medical books， prescription books from past dynasties， and modern literature， and combined with the comprehensive analysis of trait identification， hygroscopicity measurement and X-ray diffraction（XRD） detection， in order to provide a basis for understanding the original source of the mineral medicine. The results indicated that Halloysitum Rubrum was first contained in the Shennong Bencaojing， it had been consistently named Chishizhi， there were also aliases such as Chifu， Hongxinshi and Chiyouzhi. The description of Halloysitum Rubrum in ancient materia medica aligns with modern findings， categorizing it under the silicate kaolinite family， specifically polyhydrous kaolinite， with associated minerals mainly being dickite， nacrite， hematite， gibbsite， mica， etc. Historically， the production area of Halloysitum Rubrum was mainly located in the Qinling Mountains， Shandong and Henan， and is now primarily distributed in most parts of China， including Henan， Hubei and other provinces. Quality evaluation in ancient times included descriptions like "fresh and greasy color"， "delicately sticky tongue and lips" and "smooth as fat". Modern materia medica mostly evaluates its quality based on color， luster， texture and hygroscopicity， noting characteristics such as red color， smoothness， delicacy， softness and strong viscosity. Halloysitum Rubrum is sweet， sour and pungent in flavor， warm in nature， non-toxic， and belongs to the heart and large intestine meridians. It acts as an astringent and solidifying agent， particularly useful in the treatment of long-term dysentery and diarrhea， common processing methods include fire calcination， water flying， and vinegar quenching. Comprehensive analysis of the traits， XRD and humidity absorption of different batches of samples showed that the commercially available Halloysitum Rubrum is mainly bright red or brownish red， with a smooth surface like grease， soft and smooth texture， delicate cross-sectional texture， and some have waxy luster and strong water absorption. It is mainly composed of 10 Å（1 Å=0.1 nm） polyhydric kaolinite， and is often accompanied by 7 Å polyhydric kaolinite， nacrite， etc. Genuine products tend to have higher moisture absorption than counterfeit ones， which can be used as a key indicator to distinguish the authenticity. The quality evaluation of Halloysitum Rubrum aligns with historical materia medica， where "fresh color， delicate and greasy lips" could serve as a key feature for its quality evaluation.

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.

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: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.

Objective:To investigate the association between serum uric acid,pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects.Methods:All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender.The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction.Results:A total of 35 465 people were included in the study,in-cluding 16 411 men and 19 054 women.Among them,the serum uric acid concentration of men was higher than that of women,and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction.There was a negative correlation between serum uric acid level and the forced expiratory volume in one second(FEV1)and the force vital capacity(FVC)in women(P＜0.05),but in men the correlation didn't exist(P＞0.05).After adjusting for age,education,smoking status,drinking status,work strength,body mass index,history of cough,his-tory of hypertension,history of diabetes,history of dyslipidemia,white blood cells and blood albumin,the airflow obstruction in women was more likely to exist with the serum uric acid elevated(OR=1.12,95％CI:1.02-1.22,P＜0.05).The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia(OR=1.36,95％CI:1.06-1.75,P＜0.05).There was no correlation between serum uric acid concentration and airflow obstruction in men(OR=1.04,95％CI:0.96-1.13,P＞0.05),also the hyperuricemia and airflow obstruction(OR=1.12,95％CI:0.89-1.39,P＞0.05).Conclusion:There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women,and there is an association between elevated serum uric acid and airflow obstruction in women,but not in men.Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.