ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

In order to explore effective ways to reduce non-suicidal self-injury (NSSI) among female adolescents, a total of 45 female adolescent patients with NSSI in West China Hospital of Sichuan University and Guizhou Second Provincial People's Hospital from June 2021 to June 2024 were selected randomly that divided into groups A, B and C, with 15 cases in each group. Group A was treated with repeated transcranial magnetic stimulation (rTMS) and bipolar depression triple therapy, and group B was treated with bipolar depression triple therapy to compare the effectiveness and safety. Group C received bipolar depression triple therapy combined with sham stimulation which only produced stimulating sounds but no stimulating magnetic field as a control in the study. After treatment, the Hamilton Anxiety Score (HAMA), Hamilton Depression Score (HAMD) and Nurses' Global Assessment of Suicide Risk (NGASR) in group A were significantly lower than those in group B and C ( P < 0.01). rTMS combined with bipolar depression triple therapy has a definite effect on reducing NSSI in female adolescents, which can reduce the incidence rate of short-term NSSI behavior in patients.
Humans ; Female ; Adolescent ; Self-Injurious Behavior/prevention & control* ; Transcranial Magnetic Stimulation/methods* ; Bipolar Disorder/therapy* ; Combined Modality Therapy ; Treatment Outcome

OBJECTIVE: To investigate the common genotypes and distribution characteristics of thalassemia in Guiyang region, and preliminarily analyze the rare mutations of globin genes in this area. METHODS: A total of 9 334 individuals who came to our hospital for thalassemia screening from June 2016 to February 2023 were included in this study. They were examined for common thalassemia mutations using PCR-based flow-through hybridization technology. Meanwhile, rare and unknown mutations were detected by Sanger sequencing. RESULTS: Among the 9 334 cases, 895 positive cases of common thalassemia were detected, with a positive rate of 9.59%. Among the positive samples, 565 cases (63.13%) were confirmed to be α thalassemia, of which the most common genotypes were αα/-α^3.7 (46.37%), followed by αα/--^SEA(26.55%) and αα/-α^4.2(10.62%); 310 cases (34.64%) were diagnosed as β thalassemia, with β^CD17/β^N (39.35%) being the most frequent genotype, followed by β^CD41-42 /β^N (31.29%) and β ^IVS-II-654/ β^N (12.90%). There were 20 cases (2.23%) of αβ complex thalassemia, mainly being αα/-α^3.7 combined with β^CD17 /β^N . Additionally, 8 cases of rare globin gene mutations were found by Sanger sequencing, including 7 mutation types. Among them, HBB: c. -137C> T (-87 C>T) was reported for the first time in Guizhou; HBA1 : c.*29C>T and HBB : c. 93-50C>T (IVS I-81C>T) were new mutations that had not been recorded in either the HbVar or IthaGenes database. CONCLUSION Guiyang region has a high incidence of thalassemia mutations, and these mutations are diverse and complex. Analyzing gene mutation types of thalassemia in this area can contribute to the prevention of the birth of children with severe thalassemia.
Humans ; Genotype ; Mutation ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Thalassemia/epidemiology* ; Genetic Testing ; China/epidemiology* ; Male ; Female

2-substituted quinolines are the building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward method to synthesize quinolines due to its high atom economy and sustainability. However, existing chemical methods need transition metal catalysts and harsh reaction conditions. Biocatalysis with high efficiency, high selectivity, and mild reaction conditions has become an important method of organic synthesis. We mined a strain Pseudomonas monteilii ZMU-T06 capable of producing monoamine oxidase for the dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines to synthesize 2-substituted quinolines (8 substrates, yields of 45.7%-48.4%) and then hypothesized the catalytic mechanism, providing a new method for green synthesis of 2-substituted quinolines.
Quinolines/chemistry* ; Pseudomonas/classification* ; Oxidation-Reduction ; Monoamine Oxidase/biosynthesis* ; Biocatalysis

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

OBJECTIVE To provide reference for Smilax glabra quality control. METHODS UPLC method was established to simultaneously determine the contents of 5-O-caffeoylshikimic acid， neoastilbin， astilbin， neoisoastilbin， isoastilbin， engelitin， resveratrol and isoengelitin in 20 batches of S. glabra from different areas （No. S1-S20）. The quality evaluation of 20 batches of samples was performed by chemometrics； the differential biomarkers that affected the quality of S. glabra were screened. RESULTS The measured 8 components had good linear relationship within the range of measured concentration （r≥0.999 6）. RSDs of precision， repeatability and stability tests （24 h） were all lower than 2.00% （n＝6）. The average recoveries varied between 97.60% and 106.40% （RSDs were all lower than 2.00%， n＝6）. Cluster analysis showed that the samples produced in Zhejiang （S1-S5） and Jiangxi （S6-S10） were clustered into one category； the samples produced in Hunan （S11-S15） were clustered into one category； the samples produced in Yunnan （S16-S20） were clustered into one category. Principal component analysis showed that the first two principal components could represent 85.60% information of 8 components in S. glabra. Partial least squares-discriminant analysis showed that variable importance projection values of 5-O-caffeoylshikimic acid， astilbin， isoastilbin and neoastilbin were all greater than 1. CONCLUSIONS There are differences in the contents of the above 8 components in S. glabra from different origins； 5-O-caffeoylshikimic acid， astilbin， isoastilbin and neoastilbin may be differential markers affecting the quality of S. glabra.

OBJECTIVE: To discuss the influence of artificial ankle elastic improved inserts (hereinafter referred to as "improved inserts") in reducing prosthesis micromotion and improving joint surface contact mechanics by finite element analysis. METHODS: Based on the original insert of INBONE Ⅱ implant system (model A), four kinds of improved inserts were constructed by adding arc or platform type flexible layer with thickness of 1.3 or 2.6 mm, respectively. They were Flying goose type_1.3 elastic improved insert (model B), Flying goose type_2.6 elastic improved insert (model C), Platform type_1.3 elastic improved insert (model D), Platform type_2.6 elastic improved insert (model E). Then, the CT data of right ankle at neutral position of a healthy adult male volunteer was collected, and finite element models of total ankle replacement (TAR) was constructed based on model A-E prostheses by software of Mimics 19.0, Geomagic wrap 2017, Creo 6.0, Hypermesh 14.0, and Abaqus 6.14. Finally, the differences of bone-metal prosthesis interface micromotion and articular surface contact behavior between different models were investigated under ISO gait load. RESULTS: The tibia/talus-metal prosthesis interfaces micromotion of the five TAR models gradually increased during the support phase, then gradually fell back after entering the swing phase. The improved models (models B-E) showed lower bone-metal prosthesis interface micromotion when compared with the original model (model A), but there was no significant difference among models A-E ( P>0.05). The maximum micromotion of tibia appeared at the dome of the tibial bone groove, and the ​​micromotion area was the largest in model A and the smallest in model E. The maximum micromotion of talus appeared at the posterior surface of the central bone groove, and there was no difference in the micromotion area among models A-E. The contact area of the articular surface of the insert/talus prosthesis in each group increased in the support phase and decreased in the swing phase during the gait cycle. Compared with model A, the articular surface contact area of models B-E increased, but there was no significant difference among models A-E ( P>0.05). The change trend of the maximum stress on the articular surface of the inserts/talus prosthesis was similar to that of the contact area. Only the maximum contact stress of the insert joint surface of models D and E was lower than that of model A, while the maximum contact stress of the talar prosthesis joint surface of models B-E was lower than that of model A, but there was no significant difference among models A-E ( P>0.05). The high stress area of the lateral articular surface of the improved inserts significantly reduced, and the articular surface stress distribution of the talus prosthesis was more uniform. CONCLUSION Adding a flexible layer in the insert can improve the elasticity of the overall component, which is beneficial to absorb the impact force of the artificial ankle joint, thereby reducing interface micromotion and improving contact behavior. The mechanical properties of the inserts designed with the platform type and thicker flexible layer are better.
Adult ; Male ; Humans ; Ankle ; Ankle Joint/surgery* ; Finite Element Analysis ; Tibia/surgery* ; Talus ; Stress, Mechanical ; Biomechanical Phenomena

Objective To investigate the effect of different optimization algorithms on accurate reconstruction of traffic accidents. Methods Non-dominated sorting genetic algorithm-II ( NSGA-II), neighborhood cultivation genetic algorithm (NCGA) and multi-objective particle swarm optimization (MOPSO) were used to optimize the multi-rigid body dynamic reconstruction of a real case. The effects of different optimization algorithms on convergence speed and optimal approximate solution were studied. The optimal initial impact parameters were simulated as boundary conditions of finite element method, and the simulated results were compared with the actual injuries. Results NCGA had a faster convergence speed and a better result in optimization process. The kinematic response of pedestrian vehicle collision reconstructed by the optimal approximate solution was consistent with the surveillance video. The prediction of craniocerebral injury was basically consistent with the cadaver examination. Conclusions The combination of optimization algorithm, rigid multibody and finite element method can complete the accurate reconstruction of traffic accidents and reduce the influence of human factors.

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.