Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

Objective:Anterior cruciate ligament injury is the most common type of knee joint ligament injury.Anterior cruciate ligament reconstruction has a high failure rate,with bone tunnel abnormalities as the most significant factor in these failures.Digital orthopedic technology can effectively develop implementation plans for the revision,thus increasing the success rate.This study aims to develop a surgical plan for anterior cruciate ligament revision by employing multiplanar reconstruction(MPR)for measuring bone tunnel position and diameter,and simulating bone tunnel creation via 3D printing preoperatively. Methods:A total of 12 patients who underwent anterior cruciate ligament revision at the Third Xiangya Hospital of Central South University between 2014 and 2021 were retrospectively studied.The data included patient demographics,preoperative formulated knee joint 3D printing models,and preoperative knee CT scans.The study measured the bone tunnel's diameter and position to guide the establishment of revision bone tunnels during surgery,reassessed the postoperative bone tunnels,and evaluated knee joint functional scores[including International Knee Documentation Committee Knee Evaluation Form(IKDC)score,Lysholm score,and Tegner exercise level score]. Results:Preoperative measurements revealed suboptimal femoral tunnels positions in 4 patients and tibial tunnels positions in 2 patients.MPR and 3D printing technology were used to guide the establishment of a new bone canal during surgery,and postoperative measurements were satisfactory for all patients.Preoperative measurements demonstrated the interclass correlation coefficient for femoral tunnels and tibial tunnels diameters were 0.843(P<0.05)and 0.889(P<0.001),respectively.Meanwhile,the intraclass correlation coefficient were 0.811(P<0.05)and 0.784(P<0.05),respectively.The intraoperative diameter of femoral and tibial tunnels showed excellent correlation with postoperative CT measurements,with intraclass correlation coefficient values of 0.995(P<0.001)and 0.987(P<0.001),respectively.All bone tunnel positions were within the normal range.At the final follow-up,knee joint function scores in all 12 patients improved significantly compared to pre-surgery(P<0.001),and the reoperation rate was zero. Conclusion:MPR and 3D printing technology can accurately measure the parameters of reconstructed anterior cruciate ligament bone tunnels.Personalized revision plans for patients with reconstruction failure enhances the success rate of revision surgery and improves patient prognosis.

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.

Pulmonary sarcomatoid carcinoma(PSC)is a rare and highly malignant tumor,which includes the follow-ing five pathologic types:pleomorphic carcinoma,spindle cell carcinoma,giant cell carcinoma,carcinosarcoma and pulmonary blastoma.The onset of PSC is occult with non-specific clinical symptoms and signs.The clinical manifestations include irritat-ing cough,bloody sputum,dyspnea,chest pain and so on,which are closely related to the growth and invasion site of the tumor.PSC tends to metastasize early,so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit.A patient with primary PSC which led to 90%stenosis in central airway was treated by com-bined method of vascular and tracheoscopic intervention in our respiratory center.This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery.Herein we report the case for clinical reference.

Background and objective As a new technique developed in recent years,bronchoscopic interven-tion therapy has the advantages of minimal invasion,high safety and repeatability.The aim of this study is to investigate the clinical characteristics of bronchopleural fistula(BPF)induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF,so as to provide support for prevention and treatment of BPF.Methods Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Cen-ter of Dongzhimen Hospital,Beijing University of Chinese Medicine from June 2020 to September 2023 were collected.Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol,combined with blocking therapy with N-butyl cyanoacrylate,medical bioprotein glue or silicone prosthesis.Patients with fistula diameter＞5 mm were im-planted with different stents and cardiac occluders.Locations and characteristics of fistulas were summarized,meanwhile,data including Karnofsky performance status(KPS),shortbreath scale(SS),body temperature,pleural drainage volume and white blood cell count before and after operation were observed.Results For all 64 patients,96 anatomic lung resections in-cluding pneumonectomy,lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations.The proportion of fistula in the right lung(63.5％)was significantly higher than that in the left(36.5％).Besides,the right inferior lobar bronchial fistula was the most common(40.5％).After operation,KPS was significantly increased,while SS,body tem-perature,pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values(P＜0.05).By telephone follow-up or readmission during 1 month to 38 months after treament,median survival time was 21 months.33 patients(51.6％)showed complete response,7 patients(10.9％)showed complete clinical response,18 patients(28.1％)showed partial response,and 6 patients(9.4％)showed no response.As a whole,the total effective rate of broncho-scopic intervention for BPF was 90.6％.Conclusion BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating.Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Pulmonary mixed squamous cell and glandular papilloma(MSCGP)is a subtype of pulmonary papil-loma,which can be classified as central type and peripheral type based on its site of development.The central type is the most common.The clinical manifestations of pulmonary MSCGP are mainly related to the location of the tumor.Surgery is the main treatment for this disease.Bronchoscopic interventional treatment for the MSCGP in the central trachea could receive satis-factory effect.We reported a patient suffered from diffuse tracheal MSCGP who was treated by bronchoscopic interventional treatment in Respiratory Disease Center,Dongzhimen Hospital of Beijing University of Chinese Medicine,aiming to enhance the recognition of the clinical features and provide clinical references for the diagnosis and treatment of such disease.

Objective:To investigate the application of patient-based real-time quality control (PBRTQC) using exponentially weighted moving average (EWMA) method in internal quality control (IQC) procedures of thyroid function tests.Methods:The serum thyroid function test results of outpatients and inpatients in the Second Hospital of Shandong University from December 1, 2022 to April 30, 2023 were collected. Based on the PBRTQC professional intelligent software system, normality correction, parameter setting, program preparation and real-time operation of test data were carried out. The results of all patients who underwent thyroid function testing between May 1, 2023 and August 31, 2023 were used as the validation dataset. The estimated EWMA value of thyroid function test results and the cumulative coefficient of variation ( CV) over 4 months were calculated. The cumulative CV was compared with the criteria of precision quality standard (1/3TEa) and the CV of IQC. Westgard 2-2s and 1-3s rules were used for alarm setting. The early warning information of the EWMA quality control program were recorded and the potential causes of performance changes were analyzed. DxLab Mind software was used to conduct normal distribution statistics for all data, and the Kolmogorov-Smirnov test was performed on the test results. Results:The items related to serum thyroid function of the patients were all positively skewed. After data correction by Box-Cox method, the PBRTQC data of free triiodothyronine (FT3) and free thyroxine (FT4) were normally distributed, and their cumulative precisions ( CV) of EWMA within 4 months were 6.26% and 2.86%, respectively, both of which were lower than the precision quality target of 8.33%. However, the data of thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TgAb) were still positive skewed after modification. The EWMA cumulative CV of TSH, TPOAb and TgAb were 13.16%, 15.31% and 16.77%, which were higher than the precision quality targets of 8.33%, 10% and 10%, respectively. The EWMA QC program can detect different out-of-control alarms, including FT4 false alarms due to sample source concentration and TSH result bias caused by changes in reagent performance. In addition, the EWMA QC program can also detect differences in FT3 results between different DXI800 fully automated chemiluminescence instrument instruments. Conclusions:The EWMA program based on PBRTQC professional intelligent software tools can monitor the patient data of the detection system in real time and continuously, dynamically identify and monitor the errors generated during the analysis process and give early warning. It can be used as a useful supplement for the daily IQC of thyroid function items, especially FT3 and FT4, and has good clinical application value.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

Objective:To observe the clinical efficacy of combining repeated transcranial magnetic stimulation (rTMS) with radiofrequency ablation (RF) of dorsal root ganglia in treating herpes zoster infection and neuralgia.Methods:Eighty-four individuals with a herpes zoster infection who had suffered from neuralgia for no more than 7 days were divided randomly into a control group, an rTMS group, an RF group, and an observation group, each of 21. All were treated with gabapentin, valciclovir and mecobalamin. The rTMS group received rTMS treatment, 5 days per week, for 2 consecutive weeks. The RF group received RF treatment of the dorsal root ganglia on the 15th day after enrollment, while the observation group received only the medication. Before the experiment as well as after 3, 7, 16, 30 and 60 days, all of the subjects self-assessed their discomfort using a pain visual analog scale (VAS). The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Quality of Life Assessment Scale (QOL-SF36), and Pittsburgh Sleep Quality Index (PSQI) were also administered.Results:The average VAS, HAMA, HAMD, QOL-SF36, and PSQI scores of the observation group improved continuously and significantly during and after the treatment. Beyond 16 days all of those results were significantly better than the control group′s averages, and the observation group′s average VAS, HAMA and HAMD results were also significantly better than those of the rTMS group. The observation group′s average VAS, HAMA, HAMD and PSQI scores had improved significantly more than the RF group′s averages beyond 30 days.Conclusion:Combining rTMS and dorsal root ganglion RF can effectively alleviate the early pain symptoms of herpes zoster infection and neuralgia, relieve anxiety and depression, and significantly improve sleep and life quality. Such therapy is worthy of clinical promotion and application.