The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

Objective:To explore the possibility of repairing partial nasal alar defects with individualized design of localized skin flaps.Methods:The clinical data of 38 patients with nasal alar region tumor from October 2015 to June 2019 in Dalian Municipal Central Hospital were retrospectively analyzed, including 5 cases with intradermal nevus, 8 cases with junction nevus, 21 cases with basal cell carcinoma, 3 cases with trichoepithelioma, and 1 case with nasal alar sulcus fistula combined with infection. Surgical treatment with local anaesthesia was applied, and intraoperative freezing pathology was used to confirm the diagnosis and determine the safe margin. There was no nasal alar cartilage infiltration in all patients. The defect areas after resection of nasal alar lesions ranged from 1.0 cm × 1.0 cm to 3.0 cm × 2.5 cm. Local skin flap was aesthetically designed in accordance with the location and size of the nasal alar defect to primarily repair the defect. Among them, 15 cases were repaired with pedicled nasolabial groove flap, 10 cases with modified rhomboid flap, 6 cases with rotatory nasolabial groove flap, 5 cases with V-Y push flap, and 2 cases with double lobe flap.Results:One case had blood transportation obstacle after operation caused by compression and bandaging, 1 case had postoperative infection. Healing of the two cases delayed after treatment, and other patients healed properly. All the flaps survived without facial deformity, and the cosmetic effect was good.Conclusions:The primary repair of the nasal alar defect needs to follow the aesthetic requirements of the nose and face, which varies with diseases and experience of doctors. Flap selection should be individualized to achieve both the purpose of repairing defects and beauty.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed

Objective:To evaluate the effect of using a walking support band on the gait of stroke survivors.Methods:Sixty stroke survivors were randomly divided into a walking support band group ( n=20), an ankle foot orthosis (AFO) group ( n=20) and a conventional rehabilitation group ( n=20). All three groups received conventional rehabilitation therapy, while the AFO group members were additionally provided with an ankle-foot orthosis and the walking support band group members received training wearing a walking support band. Before and after 4 weeks of treatment, all three groups were evaluated using three-dimensional gait analysis. Results:A total of 57 patients finished the study. After the interventions, the average step speed, frequency and step length of the three groups had all increased significantly, while the average stride width, the percentage of double stance phase, unaffected and affected side stance phase, and the ratio between unaffected and affected side stance phase had all decreased significantly. After the intervention, the average step speed, frequency and length of the AFO and walking support band groups had increased significantly compared with the conventional rehabilitation group, while the average stride width of the AFO group, and the stride width, the percentage of double stance phase and unaffected side stance phase of the walking support band group had decreased significantly. After the treatment, the average percentages of double stance phase and unaffected side stance phase of the walking support band group had decreased significantly more than in the AFO group.Conclusions:A walking support band can significantly improve the abnormal gait of stroke survivors and is superior to an ankle-foot orthosis when combined with conventional rehabilitation therapy.

Objective    To give an annual data report of surgical treatment of esophageal cancer in Shanghai Chest Hospital to provide reference for treatment and research on esophageal cancer. Methods    The clinical data of 414 patients with esophageal cancer who underwent endoscopy (9 patients) and esophagectomy (405 patients) in Shanghai Chest Hospital in 2015 were reviewed, including 334 males and 80 females. Their tumor biological characteristics and short-term and long-term treatment results were analyzed. Results    Patients in this group were predominantly aged 60 to 69 years (46.9%), and the tumor was mainly located in the middle thorax (50.7%). About 79.9% of the patients received trans-right thoracic esophagectomy, 44.4% received minimally invasive surgery; 388 (93.7%) patients accepted upfront esophagectomy without induction therapy, and 179 (43.2%) patients received postoperative adjuvant therapy. The R0 resection rate was 90.6%, and the 30- and 90-day mortality rates were 1.4% and 2.4%, respectively. The 4-year overall survival rate of the R0 resection patients was 65.7%. Conclusion    Satisfactory long-term survival results can be obtained for thoracic esophageal cancer if R0 resection can be achieved by trans-right thoracic esophagectomy and extended lymphadenectomy combined with appropriate postoperative adjuvant treatment.

OBJECTIVE: Differentiating unicystic ameloblastomas from keratocystic odontogenic tumors (KCOT) is necessary for the planning of different treatment strategies; however, it is difficult based on conventional CT and MR sequences alone. The purpose of this study was to investigate the utility of diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADCs) in the differentiation of the two tumors. MATERIALS AND METHODS: We prospectively studied 40 patients with odontogenic cysts and tumors of the maxillomandibular region using conventional MR imaging and DWI. ADCs were measured using 2 b factors (500 and 1000). RESULTS: Unicystic ameloblastomas (n = 11) showed free diffusion on DWI and a mean ADC value of 2.309 ± 0.17 × 10-3 mm2/s. KCOT (n = 15) showed restricted diffusion on DWI with a mean ADC value of 0.923 ± 0.20 × 10-3 mm2/s. The ADC values of unicystic ameloblastomas were significantly higher than those of KCOT (p < 0.001, Mann-Whitney U-test). An ADC cut-off value of 2.0 × 10-3 mm2/s to differentiate KCOT and unicystic ameloblastomas resulted in a 100% sensitivity and 100% specificity. Dentigerous cysts (n = 3) showed restricted diffusion on DWI and similar ADC values (1.257 ± 0.05 × 10-3 mm2/s) to those of KCOT. CONCLUSION: Diffusion-weighted imaging and ADC determination can be used as an adjuvant tool to differentiate between unicystic ameloblastomas and KCOT, although the ADC values of dentigerous cysts overlap with those of KCOT.
Ameloblastoma ; Dentigerous Cyst ; Diffusion ; Humans ; Magnetic Resonance Imaging ; Odontogenic Cysts ; Odontogenic Tumors ; Prospective Studies ; Sensitivity and Specificity