OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective To compare the reflux characteristics between reflux esophagitis (RE) patients with Los Angeles (LA) classification grade A and grades B/C based on esophageal pH-impedance monitoring results. Methods A total of 74 RE patients at Zhongshan Hospital (Xiamen Branch), Fudan University from June 2021 to June 2024 were enrolled, and were divided into the LA-A group (n＝46) and the LA-B/C group (n＝28) based on the endoscopic diagnosis results. The general clinical data, symptom questionnaire score, and esophageal 24-hour pH-impedance monitoring results were compared between the two groups. Results There were no statistically significant differences in demographic data and the response rate of acid suppression therapy between the two groups. 24-hour esophageal pH-impedance monitoring results showed that there were no statistically significant differences in upright, supine, and total reflux indices, including reflux episodes, acid exposure time (AET), AET percentage (AET%), long acid reflux episodes, longest reflux duration, and total DeMeester score between the two groups. There were no statistically significant differences in distal reflux episodes, proximal reflux episodes, and high reflux (acid, weak acid, and non-acidic reflux) episodes, mean nocturnal baseline impedance (MNBI) between the two groups. The rates of pathological reflux (AET%≥6%) in LA-A group and LA-B/C group were 67.4% and 71.4%, respectively; there were no statistically significant differences in the ratio of AET% composition and the count of impedance reflux exceeding 80 during 24 h between the two groups. Conclusions LA-A grade RE based on the endoscopic diagnosis facilitates the identification of gastroesophageal reflux disease in the Chinese population

Objective To explore the strategy of intrathoracic anastomosis in patients with esophageal squamous cell carcinoma when the proximal esophagus is dilated to different degrees and explore its mechanism. Methods We retrospectively reviewed the clinical data of patients who underwent esophagectomy between 2014 and 2017 in West China Hospital. The patients were divided into two groups including a significant dilatation group with inner mucosal phase diameter (IMPD)≥17.9 mm and a non-significant dilatation group with IMPD<17.9 mm. And the patients were divided into two groups (a layered manual anastomosis group and a stapled anastomosis group) according to anastomosis method and propensity score matching was applied to adjust for potential confounders. Results We finally included 654 patients. There were 206 patients with 158 males and 48 females at average age of 62.21±7.72 years in the layerd manual analstomosis group and 448 patietns with 377 males and 71 females at average age of 62.57±8.42 years in the stapled anastomosis group. We also used Masson trichrome staining to assess the collagen fiber content in the esophagus. Compared with layered manual anastomosis, the incidence of anastomotic leakage was higher in the significant dilatation group than that in the stapled anastomosis group (original cohort: 3.8% vs. 10.7%, P=0.093; propensity score-matched cohort: 1.4% vs. 15.3%, P=0.004). And there was no significant difference in anastomotic leakage b etween layered manual anastomosis and stapled anastomosis in the non-significant dilatation group (original cohort: 4.7% vs. 4.2%, P=0.830; propensity score-matched cohort: 4.8% vs. 4.0%, P=0.206). Moreover, the average collagen fiber area ratio was significantly lower in the significant dilation group than that in the non-significant dilatation group (P=0.045). Conclusion There is a significant reduction in collagen fibers in the proximal esophageal wall tissue of esophageal squamous cell carcinoma patients with a IMPD≥17.9 mm. Intrathoracic layered manual anastomosis effectively reduces postoperative anastomotic leakage in these patients.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.

One case of knee infection after anterior cruciate ligament reconstruction caused by the gram-positive anaerobic bacterium Finegoldia magna was reported. The patient was admitted to hospital due to fever and knee joint swelling and pain after anterior cruciate ligament reconstruction. Through medical history, physical examination, imaging examination and next-generation sequencing, it was confirmed that the infection was caused by Finegoldia magna. Through literature review, 37 literatures on infectious diseases caused by Finegoldia magna was retrieved and analyzed, and the identification points of anaerobic bacteria, the application of second-generation sequencing technology and the treatment status of infection after anterior cruciate ligament reconstruction were reviewed. The incidence of infection after arthroscopic anterior cruciate ligament reconstruction is low, while anaerobic infection is even more rare and difficult to culture. The next-generation sequencing can be used to assist the diagnosis. On the basis of giving priority to the preservation of the reconstructed ligament, the combined use of arthroscopic debridement, irrigation and sensitive antibiotics is the main treatment method.

Objective To analyze the epidemiological characteristics of school varicella and varicella public health emergency event (PHEE) in Yunnan Province, and to provide a scientific basis for the prevention and control of varicella in schools. Methods The descriptive epidemiological method was used to analyze the reported PHEE of varicella in students and varicella in schools in Yunnan Province from 2018 to 2020. Results From 2018 to 2020, a total of 69,391 cases of varicella were reported in students in Yunnan Province, accounting for 71.48% (69 391 / 97 080) of the total cases in the province, and the annual average reported incidence rate was 255.56/100 000 (69 391/27.1522 million). The time distribution of the incidence showed double peaks, which were from May to July (26.48%) and October to January of the following year (53.88%). The incidence rates of different schools from high to low were 301.74/100 000 for primary schools (34 816/11.538 3 million), 250.43/100 000 for kindergarten (11 526/4.6024 million), 202.74/100 000 for middle school (16 779/8.276 1 million), and 119.07/100 000 for others (3 257/2.735 4 million). The age distribution was mainly concentrated in 5-9 years old, accounting for 39.81% (27 625/69 391). Varicella PHEE accounted for 25.64% (180/702）of the province's PHEE in the same period, school varicella PHEE accounted for 100% of varicella PHEE, and the attack rate was 3.38% (6 566/194 260). The sources of reported varicella PHEE were hospitals 45.40% (58/123), epidemic analysis 36.78% (44/123), schools 13.22% (15/123), and others 4.60% (6/123). Conclusion The incidence of varicella in schools in Yunnan Province is high, which is harmful to students. PHEE reported in rural schools are relatively lagging behind. On the basis of doing two doses of varicella vaccination, emergency prevention should be focused on epidemic seasons, lower grade schools and rural schools. The source of infection shall be controlled and managed in time to prevent the outbreak of the epidemic. It is recommended that varicella should be included in the management of Class C infectious diseases.

ObjectiveTo construct the mental health benefits of physical activity of Tai Chi and framework for college students based on International Classification of Functioning, Disability, and Health (ICF), and to systematically review the effect of physical activity of Tai Chi on anxiety, depression and sleep quality of college students. MethodsRelevant literatures about the health outcomes on anxiety, depression and sleep quality of college students participating in physical activity of Tai Chi were retrieved from databases of Web of Science, PubMed, Medline, Scopus, CNKI, Wanfang data, from the establishment to November 10th, 2022, and screened and reviewed. ResultsTen randomized controlled trials were included finally, from China and U.S.， involving 960 participants (aged 16.4 to 40 years). The main sources were from journals about physical activity and health, with publication dates from 2016 to 2021. The quality of the included literatures was evaluated using the Physical Therapy Evidence Database (PEDro) scale with a mean score of 6.3. The main mental health problems of college students mainly focused on depression, anxiety, high stress, and poor sleep quality. The physical activity of Tai Chi included 24 simplified Tai Chi and Chen style Tai Chi. The frequency of physical activity of Tai Chi was mainly 1 to 6 times a week, 45 to 90 minutes (60 minutes mostly) a time, for 4 to 18 weeks. The health benefits of Tai Chi on anxiety, depression, and sleep quality for college students in the ICF were mainly in the affective function (b152), psychomotor function (b147), energy and drive function (b130), and sleep function (b134). The beneficial outcomes of physical activity of Tai Chi involved reducing anxiety, alleviating depressive symptoms and reducing stress. Compared with physical activity of Tai Chi, physical activity of Tai Chi with the addition of a twenty-four-pattern Taijiquan theory course was more effective in improving depression levels in patients with mild and moderate depression. Tai Chi also can help to improve sleep quality, shorten the time to sleep, and reduce sleep disturbances and daytime dysfunction. ConclusionA PICO framework of Tai Chi for the health benefits of college students has been constructed using ICF. Tai Chi engaged in by college students are mainly 24 simplified Tai Chi. The frequency of physical activity of Tai Chi is 45 to 90 minutes (60 minutes mostly) a time, 1 to 6 times a week, for 4 to 18 weeks. The physical activities of Tai Chi can benefit in reducing anxiety and depression of college students and improving the quality of sleep.