Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

AIM:To observe the clinical effect of ciliary sulcus suture fixation of intraocular lens(IOL)with the scleral tunnel technique.METHODS: The clinical data of 36 patients(38 eyes)who underwent ciliary sulcus suture fixation of IOL with the scleral tunnel technique in our hospital from May 2021 to September 2023 were retrospectively analyzed. The patients were followed up for a total of 3-26 mo. The postoperative IOL position, visual acuity, refraction, intraocular pressure and complications were observed, and the results of tear film break-up time(BUT), corneal fluorescein staining(FL)and Schirmer Ⅰ test(SⅠt )were evaluated.RESULTS: The uncorrected visual acuity and best corrected visual acuity of all eyes were improved at 3 mo after surgery(all P<0.01). The differences of BUT and FL score before operation, and at 1 and 3 mo after operation were statistically significant(all P<0.05). Postoperative slit lamp examination showed the IOL of all eyes remained well positioned, and no suture erosion was observed.CONCLUSION: Ciliary sulcus suture fixation of IOL with the scleral tunnel technique is a safe, efficient, and minimally invasive procedure.

Objective:To investigate the clinical characteristics in older adult patients with sepsis and heart failure, and to analyze the influential factors of prognosis.Methods:Eighty-eight older adult patients with sepsis and heart failure who received treatment at Lishui Central Hospital from January 2020 to December 2022 were retrospectively included in the heart failure group. Eighty-eight older adult patients with sepsis, who did not have heart failure, were selected in a 1:1 ratio to form a non-heart failure group. Based on their survival status during hospitalization, the patients in the heart failure group were divided into two subgroups: the survival group and the death group. Logistic regression analysis was performed to identify the risk factors associated with the development of heart failure and adverse disease outcomes in older adult patients with sepsis.Results:There were no statistically significant differences in sex, smoking history, alcohol consumption history, history of hypertension, and history of diabetes between the heart failure group and the non-heart failure group (all P > 0.05). However, the proportion of patients aged 75 years or older in the heart failure group was 52.27% (46/88), which was significantly higher than the proportion in the non-heart failure group [34.09% (30/88), χ2 = 5.93, P < 0.05]. The proportion of patients with respiratory system infections in the heart failure group was 53.41% (47/88), which was significantly higher than the proportion in the non-heart failure group [29.55% (26/88), χ2 = 10.37, P < 0.05]. Logistic regression analysis showed that advanced age and respiratory system infections are independent risk factors for the development of heart failure in patients with sepsis. Among patients with sepsis and heart failure, 45 survived and 43 died, resulting in a mortality rate of 48.86%. The average age of patients in the death group was (76.27 ± 4.14) years, which was significantly higher than that in the survival group [(72.29 ± 4.06) years, t = 4.55, P < 0.05]. The brain natriuretic peptide level and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the death group were (636.70 ± 70.29) pg/mL and (31.93 ± 3.08) points, respectively, both of which were significantly higher than those in the survival group [(552.80 ± 54.66) pg/mL, (27.06 ± 3.80) points, t = 6.27, 6.59, both P < 0.05]. The lactate clearance rate and serum albumin level in the death group were (13.63 ± 4.84)% and (26.09 ± 4.77) g/L, respectively, both of which were significantly lower than those in the survival group [(19.94 ± 5.07)%, (30.55 ± 5.17) g/L, t = 5.97, 4.20, both P < 0.05]. Logistic regression analysis showed that in patients with sepsis and heart failure, advanced age, elevated serum brain natriuretic peptide levels, and high APACHE II scores are risk factors for poor prognosis and death. A high lactate clearance rate at 24 hours and elevated serum albumin levels are protective factors for survival. Conclusion:Advanced age and respiratory system infections increase the risk of heart failure in patients with sepsis. Advanced age, elevated brain natriuretic peptide levels, and high APACHE II scores are associated with an increased risk of death in these patients. High lactate clearance rates and elevated serum albumin levels are indicative of a reduced risk of death in patients with sepsis.

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Objective:To compare ocular surface dry eye-related indexes and tear cytokine level changes in chronic ocular graft-versus-host disease (oGVHD) patients after receiving topical treatment of 0.05% cyclosporine or 0.1% tacrolimus eye drops.Methods:A randomized controlled study was conducted.A total of 60 chronic oGVHD patients (60 eyes) were recruited at Beijing University Third Hospital from April 2020 to April 2021.The patients were divided into tacrolimus group and cyclosporine group by a random number table, with 30 patients (30 eyes) in each group.Patients in tacrolimus group used 0.1% tacrolimus eye drops (twice a day) and patients in cyclosporine group used 0.05% cyclosporine eye drops (4 times a day).Additionally, 0.1% flumetholon (twice a day), deproteinized calf blood extract (3 times a day), and 0.1% sodium hyaluronate eye drops (8 times a day) were applied for anti-inflammation and lubrication in both groups.Patients were screened according to exclusion criteria after 1-month treatment.Eventually, 21 patients (21 eyes) in tacrolimus group and 12 patients (12 eyes) in cyclosporine group were included for further study.Patients were examined before and 1 month after treatment.The primary evaluation indexes included Ocular Surface Disease Index (OSDI), corneal fluorescein staining scores and tear film break-up time (BUT).Expressions of interleukin (IL)-6, IL-8, IL-17, epidermal growth factor (EGF), and tumor necrosis factor-α (TNF-α) in tears were detected before and after treatment using Luminex chip.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.M2020489).Written informed consent was obtained from each subject before any medical examination.Results:The OSDI differences between before and after treatment were 0.4(-5.6, 2.5) in tacrolimus group and 27.2(4.6, 45.0) in cyclosporine group, and the OSDI improvement was significantly greater in cyclosporine group than in tacrolimus group ( Z=-2.547, P=0.009).The differences of corneal fluorescein staining scores and BUT between before and after treatment were 5.0(2.5, 10.0) scores and 3.5(-0.5, 13.8) seconds in tacrolimus group, 0.0(-3.0, 0.0) scores and -1.5(-3.0, 0.0) seconds in cyclosporine group, respectively, with no significantly difference between both groups ( Z=-0.526, -0.804; both at P>0.05).The differences of IL-6, IL-8, IL-17, EGF and TNF-α expressions between before and after treatment in tacrolimus group and cyclosporine group were not significantly different ( Z=-0.487, -0.112, -0.412, -1.085, -1.198; all at P>0.05). Conclusions:Altered levels of all tested cytokines in oGVHD tears are of no significant differences between tacrolimus and cyclos porine treatment.In addition, 0.05% cyclosporine eye drops may be more comfortable than 1% tacrolimus for chronic oGVHD patients.

Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.

OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.

Objective:To investigate the status of secondary victim effect of nurses in tertiary hospitals after adverse events and analyze its influencing factors.Methods:This study was a cross-sectional study. The convenient sampling method was used to select nurses from tertiary hospitals in Beijing, Shanxi and Shandong Province from October to December 2019 as the survey objects. The general information questionnaire and the Second Victim Experience and Support Tool (SVEST) were used to investigate them. Through single factor analysis of variance and multiple linear regression analysis, influencing factors of second victims of nurses were analyzed. A total of 2 163 online questionnaires were distributed and 2 040 were effectively recovered, with an effective recovery rate of 94.3%.Results:Among them, 813 nurses reported adverse event experiences, which were included in the study analysis. The total score of second victim effect of 813 nurses was (58.01±15.32) . Among the average scores of each dimension item, the score of "psychological distress" was the highest and the score of "management support" was the lowest, which were respectively (3.20±1.04) and (2.02±0.90) . The results of univariate analysis showed that there were statistically significant differences in the total scores of the second victim effect of nurses in different departments, marital status, professional title and employment nature ( P<0.05) . The results of multiple linear regression analysis showed that department, professional title and employment nature were the influencing factors of the second victim effect of nurses. The employment nature, marital status and departments had effects on the physiological distress of the second victim, and adverse event classification and departments had an effect on the psychological distress of second victims. Conclusions:The occurrence of adverse events has a moderate impact on the second victim of nurses in tertiary hospitals. Nurses are faced with more serious psychological distress, and the support they feel mainly depends on "management support", which is affected by many factors. Hospital administrators should take a positive view of the second victim effect, pay attention to the physical and mental health of nurses experiencing the role of second victim and provide effective support for different influencing factors.

The responsibility of root is absorbing water and nutrients, it is an important plant tissue, but easily to be affected by biotic and abiotic stresses, affecting crop growth and yield. The design of a synthetic root-specific promoter provides candidate promoters for the functional analysis and efficient expression of stress-related genes in crop roots. In this study, a synthetic root-specific module (pro-SRS) was designed using tandem four-copies of root specific cis-acting elements (OSE1ROOTNODULE, OSE2ROOTNODULE, SP8BFIBSP8AIB, and ROOTMOTIFAPOX1), and fused with minimal promoter from the CaMV 35S promoter to synthesize an artificially synthetic SRSP promoter. The SRSP promoter was cloned in pCAMBIA2300.1 by replacing CaMV 35S promoter so as to drive GUS expression. The constructs with SRSP promoter were transformed in tobacco by Agrobacterium-mediated method. SRSP promoter conferred root-specific expression in transgenic tobacco plants through Real-time PCR (RT-PCR) analysis and GUS histochemical staining analysis. It is indicated that the repeated arrangement of cis-acting elements can realize the expected function of the promoter. This study laid a theoretical foundation for the rational design of tissue-specific promoters.
Agrobacterium ; genetics ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Plant Roots ; genetics ; Plants, Genetically Modified ; Promoter Regions, Genetic ; genetics ; Stress, Physiological ; Tobacco ; genetics ; growth & development ; Transformation, Genetic

Objective To investigate the distribution of chronic disease and geriatric syndrome in hospitalized elderly patients with multimorbidity by chronic disease investigation and comprehensive geriatric assessment.Methods A total of 176 patients aged ≥60 years admitted into the geriatric department in our hospital were selected,and demographic factors were collected.Their chronic diseases and geriatric syndrome were recorded.The comprehensive geriatric assessment was consummated,and the biochemical indicators for chronic disease and geriatric syndrome were detected.Results All patients suffered from two or more kinds of chronic diseases.The top three most common diseases were hypertension (112 cases),diabetes (94 cases),and respiratory diseases (73cases).The sum of chronic diseases kinds were ≥3 in 137 patients,≥4 in 78 patients,≥5 in 40 patients.The amount of chronic diseases showed an increased tendency along with ageing.Totally 175 patients had more than one geriatric syndrome,the top three most common types were frailty and prefrailty(133 cases),visual impairment (117 cases),impaired daily activities (107 cases).There were significant differences in the number of geriatric syndrome among different age groups(x2 =16.989,P ＜ 0.001).Spearman analysis showed that the number of patients with geriatric syndrome were positively correlated with age(r =0.307,P＜0.001).Conclusions The prevalence of chronic disease and geriatric syndrome is high in hospitalized elderly patients with multimorbidity,which is increased with aging.We should pay attention to the screening of chronic disease and geriatric syndrome in multimorbid elderly patients