OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Objective: o develop an onset risk prediction nomogram for patients with homocysteine-type (H-type) hypertension (HTH) based on pulse diagram parameters to assist early clinical prediction and diagnosis of HTH. Methods: Patients diagnosed with essential hypertension and admitted to Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai Hospital of Traditional Chinese Medicine, and Shanghai Hospital of Integrated Traditional Chinese and Western Medicine from July 6th 2020 to June 16th 2021, and from August 11th 2023 to January 22nd 2024, were enrolled in this retrospective research. The baselines and clinical biochemical indicators of patients were collected. The SMART-I TCM pulse instrument was applied to gather pulse diagram parameters. Multivariate logistic regression was adopted to analyze the risk factors for HTH. RStudio was employed to construct the nomogram model, receiver operating characteristic (ROC) curve, and calibration curve (bootstrap self-sampling 200 times), and clinical decision curve were drawn to evaluate the model’s discrimination and clinical effectiveness. Results: A total of 168 hospitalized patients with essential hypertension were selected and divided into non-HTH group (n = 29) and HTH group (n = 139). Compared with non-HTH group, HTH group had a lower body mass index (BMI), and higher proportions of male patients and drinkers (P < 0.05). The ventricular wall thickening (VWT) could not be determined. The proportions of left common carotid intima-media wall thickness (LCCIMWT) and serum creatinine (SCR) were higher in HTH group (P < 0.05). The pulse diagram parameter As was significantly higher, and H4/H1 and T1/T were lower in HTH group (P < 0.05). Gender, alcohol consumption, serum creatinine, and the pulse diagram parameter H4/H1 were identified as independent risk factors for HTH (P < 0.05). The nomogram’s area under the ROC curve (AUC) was 0.795 [95% confidence interval (CI): (0.706 6, 0.882 8)], with a specificity of 0.724 and sensitivity of 0.799. After 200 times repeated bootstrap self-samplings, the calibration curve showed that the simulated curve fits well with the actual curve (x2 = 9.5002, P = 0.301 9). The clinical decision curve indicated that the nomogram’s applicability was optimal when the threshold for predicting HTH was between 0.38 and 1.00. Conclusion The nomogram model could be valuable for predicting the onset risk of HTH and pulse diagram parameters can facilitate early screening and prevention of HTH.

BACKGROUND:The evaluation and management of cervical vascular pathologies before orthopedic manual therapy have great significance for reducing risks,ensuring patients'interests and promoting optimal clinical decision-making.However,the research and exploration of this field in China are still in its infancy.In 2020,the International Federation of Orthopaedic Manipulative Physical Therapists(IFOMPT)released the International Framework for Examination of the Cervical Region for potential of vascular pathologies of the neck prior to Orthopaedic Manual Therapy(OMT)Intervention:International IFOMPT Cervical Framework(2020).This framework has important references and guiding values for the clinical practice of cervical manipulation in China. OBJECTIVE:To integrate and interpret the core content of the framework,to provide a reference for the clinical practice of cervical manual therapy in China. METHODS:On the basis of a full study of the framework,the authors interpret the core content of the framework from eight aspects including clinical reasoning,patient history,planning the physical examination,physical examination,risk and benefit.Meanwhile,seven databases including PubMed,EMbase,Cochrane Library,CNKI,WanFang,VIP and China Biomedical Literature Service System databases were searched by computer to screen clinical practice guidelines and expert consensus on neck pain.Through longitudinal comparison of multiple high-quality guidelines and consensus,the authors combine with the clinical practice in China to carry out discussion and analysis. RESULTS AND CONCLUSION:This framework expounds the management strategy and implementation path of cervical vascular disease evaluation before cervical manipulation from multiple dimensions,suggesting that we should improve clinicians'attention to cervical vascular disease evaluation before manipulation,and construct evaluation criteria and implementation path with Chinese clinical characteristics.Meanwhile,we should further carry out basic scientific research with multidisciplinary techniques and promote shared decision-making and teaching model innovation to achieve the best clinical decision.

Objective: To explore the association between parental education level and time spent outdoors among children, so as to provide the scientific evidence for formulating policies of myopia prevention and control among children. Methods: The study was based on secondary analysis of data from outdoor intervention studies in Shanghai. The follow up period was from March to December 2018. It included control group children ( n =1 117) with complete questionnaire surveys, ocular examinations, and time spent outdoors. Generalized linear regression models and trend tests were used to analyze the effect of parental education level on time spent outdoors among children. Results: The median time spent outdoors was 76.4(59.7, 94.6) minutes. After adjusting for covariates including children s sex and age, generalized linear regression model suggested that there was no statistical significance between father s education level and outdoor activity time ( P >0.05). Compared with children whose mothers had a junior high school education or below, children whose mothers had high school/vocational high school education, college or above had shorter time spent outdoors ( β=-6.64, -8.84 , P <0.05). Trend tests revealed that time spent outdoors among children decreased with the increase of parental education level ( P trend <0.01). Conclusions The higher the education level of fathers or mothers, the shorter time spent outdoors of children. In addition to highlight outdoor activities at school, myopia prevention and control efforts should be focused on the role of parents in increasing children s outdoor activities.

Objective:To explore the factors associated with vascular luminal dilatational remodeling (VLDR) following balloon angioplasty for intracranial atherosclerotic stenosis (ICAS).Methods:A case-control study was conducted to analyze the data of symptomatic severe ICAS patients who received either paclitaxel-coated balloon angioplasty (PCBA) or plain balloon angioplasty (POBA) at our center from January 2019 to January 2022 and completed the six-month follow-up. The patients were divided into VLDR group and non-VLDR group according to whether VLDR occurred on follow-up digital subtraction angiography (DSA). The baseline data, preoperative and postoperative lesion characteristics (DSA), and perioperative related information were collected. The definition of VLDR was a decrease in luminal stenosis rate by more than 10% at the time of follow-up compared to the immediate postoperative period. Multivariate logistic regression was performed to analyze possible factors affecting VLDR such as balloon type, balloon length, and expansion time.Results:A total of 88 patients were included in this study, with 16 in the VLDR group and 72 in the non-VLDR group. The follow-up time for all included patients was 6.00 (5.00, 7.00) months. VLDR occurred in 18.2% (16/88) of cases, with a VLDR incidence of 30.4% (14/46) after PCBA and 4.8% (2/42) after POBA. Univariate logistic regression analysis revealed that treatment balloon type, balloon length, inflated time, immediate postoperative stenosis rate, follow-up time and Mori classification may affect the occurrence of VLDR. Multivariate logistic regression analysis showed that the use of paclitaxel-coated balloon (PCB) ( OR=9.82, 95% CI 1.99-48.49, P=0.005) and postoperative immediate stenosis rate ( OR=1.07, 95% CI 1.00-1.14, P=0.042) were independently associated with VLDR. Conclusion:The occurrence of VLDR following balloon angioplasty in ICAS was associated with the use of PCB and immediate postoperative stenosis rates, which will provide guidance for the clinical application of PCB.

Objective:To report single-center clinical experience with endovascular recanalization for non-acute symptomatic intracranial vertebral artery occlusion, to assess the feasibility and safety of endovascular recanalization and to propose the benefit group for selected patients.Methods:From January 2019 to December 2021, 92 patients with non-acute symptomatic intracranial vertebral artery occlusion who underwent endovascular recanalization were retrospectively analyzed. The patients were divided into three groups (low, medium and high-risk group) according to occlusion length, occlusion duration, occlusion nature, calcification of the occlusion segment, and occlusion angulation, and the indicators of patients in each group were analyzed, including the general baseline data of the patients, surgical status and follow-up results. The technical success and perioperative complication rates of low, medium and high-risk groups were calculated. Meanwhile, the differences between three groups were evaluated using the χ2 test for trend or ANOVA analysis. Results:The overall technical success rate of endovascular recanalization was 83.7% (77/92), and the perioperative complication rate was 10.9% (10/92). Among the 3 classification groups, the recanalization success rate from the low-risk group to the high-risk group was 100%, 93.3%, 27.8%( P=0.047), and gradually decreased; while the overall perioperative complication rate was 0, 10.0%, 38.9% ( P=0.001), and gradually increased; the proportion of 90-day mRS score 0-2 was 100%, 83.3%, 22.2% ( P=0.026), and progressively decreased; 77 patients with successful recanalization were followed up, the rate of restenosis/reocclusion was 0, 17.9%, 80.0%( P=0.001), and progressively increased. Patients in the low-and intermediate-risk groups performed well with endovascular recanalization. In 88 patients (4 patients lost to follow-up), a median clinical follow-up of 13 (7, 16) months, stroke or death beyond 30 days was 17.4% (16/92). Conclusions:Endovascular recanalization is safe and feasible for reasonably selected patients with non-acute symptomatic intracranial vertebral artery occlusion, especially in low-and medium-risk groups, and it also provides an alternative to conservative therapy for patients with non-acute symptomatic intracranial vertebral artery occlusion.

Objective:To investigate the resistance of Culex pipiens pallens to pyrethroid insecticides in Hangzhou City, and explore the mutation of knock down resistance (kdr) gene of Culex pipiens pallens, providing scientific basis for control of Culex pipiens pallens in the region. Methods:In September 2022, larvae and pupae of Culex pipiens pallens were collected from various locations at national monitoring sites in Shangcheng District and Gongshu District of Hangzhou City. They were bred in the laboratory and their resistance to three commonly used pyrethroid insecticides (permethrin, deltamethrin and beta-cypermethrin) was determined using the adult mosquito contact tube method and larval immersion method recommended by the World Health Organization. The genomic DNA was extracted from individual adult mosquito, and kdr gene mutation was detected via PCR amplification and Sanger sequencing. Results:The 24-hour mortality rates of adult mosquitoes of Culex pipiens pallens exposed to 0.25% permethrin, 0.025% deltamethrin, and 0.025% beta-cypermethrin were 20.00% (15/75), 17.33% (13/75), and 18.67% (14/75), respectively, indicating resistance. The resistance ratios of Culex pipiens pallens larvae to permethrin, deltamethrin, and beta-cypermethrin were 27.08, 341.00, and 15.88, respectively. Among 183 adult mosquitoes that survived under the diagnostic doses of pyrethroid insecticides, 180 mosquitoes (98.36%) had mutation at the L1014 site of the kdr gene. Among 42 adult mosquitoes that died under the diagnostic doses of pyrethroid insecticides, 5 mosquitoes (11.90%) had L1014 mutation in the kdr gene. Conclusions:Culex pipiens pallens in Hangzhou City has developed varying degrees of resistance to permethrin, deltamethrin and beta-cypermethrin, with a high frequency of kdr gene mutation in resistant mosquitoes. We should strengthen the monitoring of the resistance of Culex pipiens pallens in Hangzhou City and use chemical insecticides reasonably.

Objective:To investigate the distribution and seasonal fluctuations of flies in Hangzhou, study the resistance of Musca domestica ( M. domestica) to five commonly used sanitary insecticides and changing patterns in Hangzhou and provide a basis for scientific control of flies. Methods:From April to November 2023, the cage trap method was used for ecological monitoring of flies. From May to June 2023, the swing net method was used to collect M. domestica from various districts (counties and cities) in Hangzhou. After indoor breeding, the resistance of F1 generation female adult flies to five commonly used sanitary insecticides was determined using the micro-drop method. Probit regression model was used to calculate the median lethal dose (LD 50), 95% confidence interval ( CI) and virulence regression equation. Results:In 2023, the fly density in Hangzhou was 5.99 flies/cage, with a higher density of flies belonging to the Sarcophagus family (2.39 flies/cage), making it the dominant fly species in Hangzhou. Among different monitoring points, the fly density in Linping District was relatively high (20.97 flies/cage). In different habitats, the fly density in agricultural markets was relatively high (fly density from April to November: 2.86, 5.39, 8.86, 16.86, 31.32, 6.39, 3.75 and 1.89 flies/cage). The seasonal fluctuation of fly density showed a unimodal pattern, with the higher density in August (13.45 flies/cage). The M. domestica population in Hangzhou was sensitive to dichlorvos [resistance ratio ( RR): 3.08 times]. Different degrees of resistance were developed to propoxur, deltamethrin, beta-cypermethrin, and beta-cyhalothrin. The degree of resistance from high to low was propoxur (> 336.36 times), beta-cypermethrin (906.61 times), beta-cyhalothrin (432.29 times), and deltamethrin (72.56 times). Based on the monitoring results from 2003 to 2023, the RR of dichlorvos reached the higher level in 2008 (33.47 times) and gradually decreased to a sensitive level. The resistance level of propoxur had been at an extremely high level over the years. Three types of pyrethroid insecticides all had high resistance. Conclusions:The species of flies in the Sarcophagus family are the dominant population in Hangzhou, and M. domestica has developed high resistance to four commonly used insecticides except for dichlorvos. The use of physical control techniques is advocated to reduce the use of chemical pesticides, and prevent the continuous increase of resistance in M. domestica.

ObjectiveThis study aims to investigate the changes in fungal community diversity and volatile components during the aging process of Aquilariae Lignum Resinatum and explore the internal relationship between them. MethodAquilariae Lignum Resinatum samples with different aging years were collected. High-throughput sequencing was employed to analyze the fungal diversity and abundance， and α and β diversity indicators were calculated to reveal the composition and dynamic changes of the fungal community. In addition， the essential oils of Aquilariae Lignum Resinatum with different aging years were extracted， separated， and identified by two-dimensional gas chromatography-high resolution time-of-flight mass spectrometry. ResultA total of 61 compounds were identified from the volatile components of five groups of Aquilariae Lignum Resinatum samples， including 2 monoterpenes， 24 sesquiterpenoids， 1 diterpene， 13 aromatic hydrocarbons， 9 alkanes， and 12 other compounds. Among them， the volatile compounds isolated from the sample aged for 1 year had the largest number， and those from the sample aged for 2 years accounted for the largest proportion of the total components. The internal transcribed spacer（ITS） amplicon sequencing revealed that the fungi in the five groups of samples belonged to 162 genera. Kirschsteiniothelia， Aspergillus， Lasiodiplodia， Phaeoacremonium， and Trichoderma were the dominant fungal genera. The fungal diversity in the Aquilariae Lignum Resinatum sample aged for 4 years was significantly higher than that in the samples aged for 0 to 3 years. ConclusionThe volatile component content and composition of Aquilariae Lignum Resinatum altered dramatically during aging. The aging of Aquilariae Lignum Resinatum was accompanied by the increasing fungal diversity， decreasing relative content of aromatic hydrocarbons， and increasing relative content of sesquiterpenoids. In general， aging was beneficial to the transformation of sesquiterpenoids and the enrichment of fungi.