Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

ObjectiveTo analyze and construct a curriculum framework and content system of the vocational college rehabilitation therapy technology exercise therapy technology course, based on World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) and rehabilitation competency framework (RCF). MethodsUsing educational psychology and curriculum theory, and applying the ICF and RCF, the curriculum system for rehabilitation therapy technology curriculum system was constructed. A systematic analysis of the existing exercise therapy technology course content was conducted to identify the core elements related to ICF and RCF. Through the design of course modules, these core elements were integrated into theoretical courses, skills training and practical courses to form a comprehensive curriculum structure. ResultsCombining the ICF and RCF, a curriculum system for rehabilitation therapy technology curriculum system was constructed, covering theoretical courses, skills training and practical courses. This system enabled students to systematically master rehabilitation assessment and treatment techniques and develop clinical decision-making abilities and interdisciplinary collaboration skills. The introduction of the ICF framework allowed students to acquire knowledge, skills and abilities in the field of exercise therapy technology through the course. Developing competency-oriented courses based on RCF framework helped students develop comprehensive professional competencies through learning. ConclusionBy integrating the ICF and RCF, a curriculum for exercise therapy technology course in vocational colleges has been constructed. Based on the ICF framework, the content of the course has been aligned with the bio-psycho-social theory of functioning and health, covering three levels: body function, activity and participation, and environmental factors. The curriculum content should include the analysis, assessment and intervention of these functioning. RCF provides a theoretical structure and methodology for developing competency-oriented courses. When designing the course modules, teaching objectives have been established based on the core competency framework, aiming to develop students' comprehensive professional competence and professionalism through theoretical courses, practical training and clinical internships.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the correlation between right-to-left shunt (RLS) and infarct pattern in patients with cryptogenic stroke.Methods:Young and middle-aged patients with acute cryptogenic stroke admitted to the Department of Neurology, Xiaogan Central Hospital from May 2016 to January 2020 were enrolled retrospectively. The demographic data, vascular risk factors, baseline blood pressure, laboratory findings, stroke severity, infarct location and distribution pattern were documented. The patients were divided into RLS group and non-RLS group according to the findings of the transcranial Doppler ultrasound foaming test. They were divided into single lesion group and multiple-lesion group according to the findings of diffusion-weighted imaging. Multivariate logistic regression analysis was used to identify the correlation between RLS and infarct pattern. Results:A total of 68 patients with acute cryptogenic stroke were included, 37 of them were male (54.4%), and their age was 47.63±6.57 years (range, 31-59 years). Thirty patients (44.1%) had RLS, including 22 (73.3%) with mild shunt and 8 (26.7%) with severe shunt. The proportions of men, cortical-subcortical infarction and multiple blood supply area lesions in the RLS group were significantly higher than those in the non-RLS group, while triacylglycerol, body mass index, the proportions of patients with subcortical infarction and single lesions in the single vessel blood supply area were significantly lower than those in the non-RLS group ( P<0.05). The proportions of patients with anterior circulation+ posterior circulation infarction, cortical-subcortical infarction, and RLS in the multi-lesion group were significantly higher than those in the single-lesion group, while the proportion of patients with subcortical infarction was significantly lower than that in the single-lesion group (all P<0.05). Multivariate logistic regression analysis showed that RLS was an independent risk factor for multiple infarctions (odds ratio 6.681, 95% confidence interval 1.206-37.019; P=0.030). Conclusion:RLS is independently associated with multiple infarctions in patients with cryptogenic stroke.

Objective:To explore the characteristics of cognitive impairment in elderly adults with deafness and assess its influencing factors.Methods:This was a cross-sectional study.From July 2015 to July 2017, 117 elderly patients with age-related hearing loss(presbyacusis group)admitted to Otolaryngology Clinic of the Yangzhou University Affiliated Hospital and 97 healthy elderly adults(control group)undergoing healthy physical examination in the same period were included.We evaluated the cognitive function was with Montreal cognitive assessment(MoCA)scale Chinese version, and calculated their MoCA total score, and recorded the clinical data and the hearing loss level.The correlation between hearing loss level and MoCA was analyzed.Results:The total scores of MoCA was significantly lower in the presbyacusis group(21.6±5.8)than that in the control group(26.8±1.5)( t=8.49, P<0.05). Patients in the presbyacusis group were associated with significantly lower levels of visuospatial and executive function(4.1 ± 0.9 vs.4.8 ± 0.5), naming(2.2 ± 1.0 vs.3.0 ± 0.0), attention(5.2 ± 1.7 vs.5.9 ± 0.5), language(2.0 ± 0.9 vs.3.0 ± 0.2), abstraction(1.6 ± 0.5 vs.1.9 ± 0.3), delayed recall(1.8 ± 0.7 vs.2.2 ± 0.4), orientation(4.4 ± 1.2 vs.5.8 ± 0.4)than the control group( all P <0.05). The level of hearing loss was negatively correlated with the total scores of MoCA and all the subscale of MoCA(all P<0.01). Univariate analysis showed that age, educational level, marital status, hearing loss level, course of hearing loss, and hearing aid were correlated with MoCA total score in elderly patients with presbcyusis(all P<0.05). Multiple linear regression analysis showed that marital status( t=6.596, P<0.05), and hearing aid( t=2.182, P<0.05)were positively correlated with MoCA total score, and age( t=-2.691), the educational level( t=-2.691), hearing loss level( t=-7.626), and course of hearing loss( t=-6.11)was negatively associated with MoCA total score(all P<0.05). Conclusions:Cognitive function is generally decline in elderly patients with presbycusis, and age, educational level, marital status, the course of hearing loss, hearing loss level and whether or not hearing aid are important factor affecting cognitive function in elderly patients with presbycusis.

Sixty-three elderly patients with allergic rhinitis and symptoms of anxiety and depression attending in the Affiliated Hospital of Yangzhou University from August 2016 to August 2018 were randomly divided into two groups: 30 patients received deanxit combined with anti-allergic drugs for treatment (study group) and another 30 patients received anti-allergic drugs treatment alone (control group). Subjective nasal obstruction was evaluated by Visual Analogue Scale (VAS), and the quality of life of patients was assessed by Rhinoconjunetivitis Quality of Life Questionnaire (RQLQ).The anxiety and depression mood changes were assessed by Self-rating Anxiety Scale (SAS) sand Self-rating Depression Scale (SDS).The scores of symptoms and mood were compared after 4 weeks and 8 weeks of treatment. The clinical nasal symptoms VAS score, the total RQLQ scores and its 7 domains scores, SDS and SAS scores of patients in two groups were significantly reduced compared to those before treatment ( P<0.05). The VAS score, the total of RQLQ scores and its 7 domains scores, SDS and SAS scores were significantly lower in the study group than those in the control group after 4 weeks and 8 weeks of treatment.The total effective rate of study group was significantly higher than those of the control group (χ 2=6.922, P=0.031; χ 2=11.544, P=0.003). Deanxit combined with anti-allergic drugs shows significant clinical efficacy, it also can improve the symptoms of anxiety and depression, and the quality of life for elderly patients with allergic rhinitis.

Objective To investigate the psychopathological characteristics in families of presbycusis patients and its influencing factors.Methods The psychopathological characteristics were evaluated with the Symptom Checklist-90(SCL-90) Chinese version in 157 families of presbycusis patients(FPP) in the Affiliated Hospital of Yangzhou University from July 2015 to July 2017. Somatization, obsessive - compulsive disorder, interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,paranoid ideation,psychoticism and other were assessed and compared with the Chinese standard norm.The correlation between SCL-90 and related data had also been analyzed. The general information and clinical data of patients were analyzed.Results The SCL-90 score in the FPP group was (146.3 ± 42.8)points.The total score and total average score of SCL-90 had statistically significant difference between the FPP group and the Chinese standard group(t=14.557,14.765,all P<0.05).The scores of somatiza-tion,interpersonal sensitivity,depression and anxiety factors in the FPP group were higher than those in the Chinese standard group(t=5.417,13.588,20.857,22.475,all P<0.05).Age,sleeping condition,educational level,hearing aids and the level of patients＇hearing loss were correlated with the total score of SCL-90( TSCL-90) in FPP( all P<0.05).Multiple linear regression analysis showed that age(t=2.550,P<0.000),the educational level( t =4.087,P<0.000),and the level of patients＇hearing loss ( t =2.188, P <0.05 ) were positively correlated with TSCL-90,and sleeping condition(t= -2.004,P<0.05) and hearing aids(t= -4.643,P<0.05) were negatively associated with TSCL-90.Conclusion The psychopathological characteristics are generally poor in families with presbycusis patients,accompanied by obvious depression and anxiety;and age,sleeping condition,educational level, hearing aids and the level of patients＇hearing loss are important influencing factors.It is important to pay attention to overall health in families with presbycusis patients.

Objective: To explore the reliability, validity and best cut-off value of Chinese version Addenbrooke's cognitive examination-Ⅲ(ACE-Ⅲ) in presbycusis patients with mild cognitive impairment(MCI). Methods: A total of 43 presbycusis patients with mild cognitive impairment, 61 presbycusis patients with normal cognitive impairment and 60 healthy controls treated in outpatient clinic of department of otolaryngology in the Affiliated Hospital of Yangzhou University from January 2016 to October 2017 were enrolled.The Chinese version of mini mental state examination(MMSE), Montreal cognitive assessment(MoCA) and ACE-Ⅲ were used to evaluate cognitive function of subjects.The reliability and validity of the ACE-Ⅲ were analyzed with the SPSS 21.0, and the cut-off point was confirmed with the receiver operating characteristic(ROC) curve analysis, and the value of the scale questionnaire in the diagnosis of presbycusis patients with MCI was assessed. Results: Chinese version of ACE-Ⅲ had betler feasiblity, and the receiving rate, recovery rate and effivience were 100.0%, 100.0% and 94.9%, respetively.The Cronbach's alpha, split-half reliability and intraclass correlation coefficient were 0.870(P<0.05), 0.874(P<0.05) and 0.880(P<0.05), respectively.The patients in MCI group got a lower score in the sub-scale of attention/orientation, memory, verbal fluency, language and visual space of ACE-Ⅲ compared with those in NCI group and healthy control group, and the differences were statistically significant (F=48.042, 46.594, 35.442, 19.374, 256.19, 140.319, all P<0.001). The criteria validity calculated between the Chinese version of ACE-Ⅲ and MMSE was 0.802 (P<0.001). Factor analysis of the construct validity showed that the 26 items were classed into five domains.Every domain was sensitive and effective to discriminate between patients and healthy individuals(P<0.05). The Chinese version of ACE-Ⅲ showed significantly correlation with the total scores of MoCA(r=0.802, P<0, 001). When the cut-off value for diagnosis was 86.5, the largest area under the ROC curve for the Chinese version of ACE-Ⅲ was 0.98(95% CI: 0.897-0.996). The relative sensitivity and specificity were 100.0% and 95.0%, respectively. Conclusion The Chinese version of ACE-Ⅲ had better internal consistency, reliability and validity, and is applicable for MCI assessment in elderly patients with presbycusis.Patients with presbycusis can be considered to have cognitive dysfunction with score of 86.5 by using this questionnaire.

Objective To evaluate the quality of life,emotional symptoms (anxiety and depressive symptoms)and their influencing factors in elderly patients with presbycusis.Methods From May 2015 to May 2017,288 patients with presbycusis and 123 healthy controls were consecutively included into this study.Quality of life and emotional symptoms were evaluated by a series of questionnaires including the generic questionnaire medical outcomes study short-form 36 items health survey(SF-36),self-rating depression scale (SDS) and self-rating anxiety scale (SAS).Results The prevalences of anxiety(SAS score≥50)and depression(SDS scores≥53)were 23.3％ (67/288)and 20.1％(58/288),respectively;and the prevalence of the two in combination was 13.2％ (38/288).When assessed with SF-36,the scores of physical functioning,physical role,bodily pain,general health,social functioning,emotional role,and mental health were 71.0 ± 9.0,77.3 ± 9.1,73.3 -±9.6,69.6±8.6,71.9±9.9,72.1±12.7,and 73.1±10.5,respectively,which were lower than those in the control group(82.1±10.2,82.4±4.3,86.4±11.3,2.1±7.9,82.8±9.9,83.1±7.7,and 82.2 ±3.6,respectively;all P＜0.05).The scores of SDS and SAS in the presbyacsis group were 53.2± 13.3 and 51.9 ± 11.2,respectively,which were higher than those in the control group(42.5± 10.3 and 43.9± 6.2,respectively;t =10.09 and 7.52,respectively;all P＜0.05).SDS was negatively correlated with general physical and mental health (r =-0.787,P ＜ 0.05;r =-0.743,P ＜ 0.05);SAS was negatively associated with general physical and mental health(r =-0.801,P ＜0.05;r =0.750,P＜0.05,respectively);and SDS was positively correlated with SAS(r =0.958,P ＜0.05).Multiple linear regression analysis showed that concomitant hearing impairment,educational level,marital status,living condition,and sleep condition were positively correlated with SF-36 general health scores;severity of hearing loss and number of comorbidities were negatively associated with general health.However,severity of hearing loss,concomitant hearing impairment,educational level,marital status,and number of comorbidities were positively correlated with SAS and SDS scores;educational level and sleeping were negatively associated with SAS and SDS scores.Conclusions Poor quality of life and high prevalences of depression and anxiety are found in elderly patients with presbycusis,and their influencing factors include severity of hearing loss,concomitant hearing impairment,education level,marital status,sleeping and number of comorbidities.

BACKGROUND: Pedicle screws are widely used in spinal internal fixation, while complications related to screw mistaken placement can be found occasionally. Conventional imaging examination cannot provide the accurate situation of the nail, and the nail path can be directly revealed on CT.OBJECTIVE: To discuss the application of CT scanning in the preoperative planning of lumbar spine surgery using digital technology.METHODS: 136 patients were enrolled, and digital technology was used to determine the best nailing track on planar CT images. Then the length of the pedicle screws, width of the pedicle, angle between pedicle screws and standard sagittal plane, and angle between pedicle screw and spinous process as well as sagittal plane were measured. The difference in measured values on each side was compared. Also, the difference in angle between pedicle screw and sagittal plane and spinous process was compared.RESULTS AND CONCLUSION: (1) There was no significant difference in the length of pedicle screw in both sides (P > 0.05). (2) There was significant difference in the width of pedicle screw at L1 and L4 of two sides (P < 0.05). (3) The angle between pedicle screw and standard sagittal plane at each level bilaterally did not differ significantly (P > 0.05). (4) The angle between pedicle screw and spinous process at each level bilaterally did not differ significantly (P > 0.05). (5) To conclude, pedicle CT scanning can accurately reflect patients' pedicle anatomic situation, which can help surgeons to design an appropriate scheme. Moreover, the anatomical variations of lumbar spine are remarkable, so pedicle screw insertion should be planned individuality.