Objective To analyze the levels of serum CTCs and ctDNA in NSCLC patients receiving first-line EGFR-TKI treatment, and to explore the clinical value of CTCs and ctDNA detection in assessing the efficacy of treatment for advanced lung cancer. Methods A total of 109 NSCLC patients receiving first-line EGFR-TKI treatment were enrolled. Serum tumor markers CEA, CTCs, and ctDNA were detected at baseline and after one month of treatment. Chest CT scans were performed, and treatment efficacy was evaluated based on RECIST1.1 criteria. CTCs were counted by enrichment-staining-computational algorithm to analyze malignant features, while ctDNA was assessed using digital PCR. Results Survival rate was low in patients with abnormal CEA and ctDNA tests at baseline and in patients with reduced serum CTCs after treatment. In the SD subgroup of patients with brain metastases and advanced stage, the PFS benefit was low. Conclusion Patients in the SD subgroup have significantly higher recurrence risks than those in the PR or CR subgroups. Therefore, CTC and ctDNA testing should be applied to patients in the SD subgroup to identify high-risk patients with poor response to EGFR-TKI treatment, intervene with additional treatment promptly, and obtain long progression-free survival.

Objective: To design HBV DNA proficiency testing and system comparison samples with different concentration gradients, analyze their detection results in PCR detection systems, evaluate the nucleic acid detection capabilities of laboratories and differences between detection systems, and put forward suggestions for continuous quality improvement to participating laboratories. Methods: Three groups of randomly numbered proficiency testing samples (with HBV DNA reference concentrations of <2, 7.5, and 30 IU/mL respectively) were taken as the detection objects. Using nucleic acid test data from 11 provincial blood station laboratories as the source, the samples were grouped by detection system and laboratory successively, and statistical analysis was conducted. Results: Statistical analysis of the detection data of the three groups of samples based on detection systems and laboratories showed that from low to high concentration, the coincidence rate between the detection results of different detection systems and laboratories and the expected results showed an increasing trend: 38.89%, 85.90%, and 100.00%; the same system exhibited certain differences in performance among different laboratories. Conclusion: Through this proficiency testing and system comparison, it is found that there are certain differences in the detection capabilities of different laboratories and different nucleic acid test systems. Blood station laboratories should standardize processes, strengthen quality management and data analysis on the basis of being familiar with the detection performance of their detection systems, and at the same time strengthen the control of laboratory interference factors to continuously improve the nucleic acid detection capabilities of blood station laboratories.

Objective:To explore the effectiveness of varenicline on smoking cessation.Methods:In this cross-sectional study, a total of 318 tobacco-dependent adults with complete medical record were included from January 2018 to June 2023 in the First Affiliated Hospital of Soochow University. All the patients received smoking cessation advices and exhaled carbon monoxide (eCO) detection on initial visit and 3 months later. According to whether they received varenicline, the participants were divided into smoking cessation advices (SCA) group (126 cases) and varenicline (VAR) group (192 cases). The follow-up period was≥3 months. Quit smoking for at least 3 months was regarded as successful smoking-cessation.Results:eCO levels on enrollment and 3 months later for SCA group and VAR group were (11.5±4.8) vs (11.8±4.3) ppm and (7.8±3.6) vs (7.3±4.3) ppm ( P=0.550, 0.239). eCO levels of SCA group and VAR group decreased significantly 3 months later ( t=7.293, 11.920, both P<0.001). Participants in VAR group had significantly higher odds of abstinence than those in SCA group (40.6% vs 28.6%, χ2=4.806, P=0.028). After quit smoking successfully, eCO levels decreased from (15.5±5.6) and (13.9±5.1) ppm to (3.6±2.4) and (3.5±2.5) ppm ( t=17.580, 27.180, both P<0.001) for SCA group and VAR group respectively. Conclusion:Varenicline usage can increase the abstinence rates of tobacco-dependent adults.

This article reported a set of triplets with type V osteogenesis imperfecta (OI) caused by heterozygous variation in the interferon-induced transmembrane protein 5 ( IFITM5) gene. The triplets developed shortness of breath and multiple fractures at 21, 16, and 17 d after birth, respectively. On theadmission, scattered speckled patterns and hard swelling were observed in all three triplets during physical examination; several blisters were found on the right wrist of the second triplet; the smallest triplet had scattered blisters and ulcers in the mouth, complicated by neonatal sepsis, shock, respiratory failure, necrotizing enterocolitis, and intracranial infection. Whole-exome sequencing identified a pathogenic mutation in the triplets, that was located in the 5'-untranslated region of the IFITM5 coding gene, where a base C was converted to T (c.-14C>T). IFITM5 gene of the triplets. IFITM5 gene mutation can result in type V OI, which is inherited in an autosomal dominant pattern. Based on the clinical phenotype caused by the variation in the IFITM5 gene and literature review, the triplets were diagnosed with congenital type V OI. After respiratory support, anti-infection treatment, and symptomatic support treatment, all three triplets were discharged with improved condition. They were followed up to the age of three years and their nutritional status were good. However, their gross motor development was slightly delayed, and they all experienced different degrees and sites of bone fractures again.

Objective To compare and analyze the differences between customized models and commercial universal models in the segmentation of organs-at-risk in cervical cancer,and to investigate the feasibility of customized models.Methods A retrospective analysis was conducted on 270 cervical cancer patients.Senior clinicians manually delineated organs-at-risk,including the bladder,rectum,small intestine,pelvic bone marrow,femoral heads,and kidneys.The cases were randomly selected to develop customized models,with 202 cases allocated to the training set,38 cases to the test set,and 30 cases to the validation set.The universal and customized models were used for segmentation on the test set,and the automatic segmentation results obtained by the two models were compared with manual segmentation results to assess the performance of the customized model.Results Both customized model and universal model had comparable DSC values to manual segmentation,demonstrating satisfactory delineation outcomes(DSC values ranging from 0.7 to 0.9).However,in terms of deviation of centroid and 95％Hausdorff distance,the customized model surpassed the universal model.Conclusion Compared with the universal model,the customized model offers superior accuracy in delineating the structures of organs-at-risk in cervical cancer.As the customized model is optimized based on specific datasets,it provides precise support for clinical decision-making and holds promising applications in the treatment of cervical cancer.

Active physical exercise can effectively alleviate the pathological process of chronic cerebral ischemia(CCH)and improve learning and memory ability.This paper reviews the possible biological mechanisms of aerobic exercise to delay the pathological process of chronic cerebral ischemia and improve learning and memory.Previous studies have found that aerobic exercise can improve the neuroprotective effect,enhance the plasticity of hippocampal synapses,improve the activity of the upper and lower pathways of hippocampal tissue,and improve learning and memory ability.However,the intervention effect of aerobic exercise on chronic cerebral ischemia should be fully considered at the intervention time,and the intervention effect is also different.

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

Objective:To investigate the diagnosis of dual-energy X-ray absorptiometry(DXA)for osteoporosis(OP)of postmenopausal patients with rheumatoid arthritis(RA)in Qinghai region and the risk factors of them.Methods:A total of 200 postmenopausal female RA patients who admitted to Qinghai Hospital of Traditional Chinese Medicine from May 2022 to April 2023 were selected.All patients were tested for bone mineral density(BMD)after admission,and lumbar spines L1-L4,whole lumbar,large trochanter,Ward's triangle area,whole body and whole forearm were measured by DXA.According to the results of BMD test,patients whose BMD T values of all body parts-2.5 SD were less or equal to-2.5 were included in the OP group(121 cases),and patients whose BMD T value of all body parts were larger than-2.5 SD were included in the non-OP group(79 cases).The BMD T value of different body parts between two groups of RA patients were compared and analyzed.The area under curve(AUC)of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of BMD T value for OP.The logistic regression method was adopted to analyze the risk factors that postmenopausal RA patients of Qinghai region occurred OP.Results:The BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangular area,whole body and whole forearm of OP group were obviously lower than those of the non-OP group.In analysis of ROC curve,the sensitivities of BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangle area,whole body and forearm were respectively 96.20%,95.22%,90.16%,96.03%,92.01%,89.36%,99.26%,90.02% and 96.03% in diagnosing OP,and the specificities of them were respectively 81.00%,82.19%,85.22%,83.06%,83.06%,90.22%,80.06%,86.23%,83.09%,and the AUC values of them were respectively 0.908,0.905,0.896,0.906,0.903,0.879,0.918,0.901 and 0.906.The results of the logistic-regression analysis showed that advanced age,long disease course,rheumatic activity scores of 28 joints,erythrocyte sedimentation rate and Calcium supplementation were the risk factors of occurring OP in postmenopausal RA patients in Qinghai region.Conclusion:The DXA method that detects BMD of RA patients who occur OP can be used as gold standard to assess OP,and there are many risk factors that affect the occurrence of OP in postmenopausal RA patients of Qinghai region.The clinical work should combine with relative factors to formulate reasonable measure so as to reduce the incidence of OP.

Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.

Objective:To determine the relationship between tibial plateau stresses and malunion by exploring the changes in mechanical conduction in the knee joint after malunion of Hoffa fracture of the tibial plateau.Methods:This study selected 28 knee joint specimens treated with formalin for preservation, half of which were from male and half from female individuals with an age of (51.4±9.5) years. Their structures were intact, and flexion-extension activities normal. X-ray examinations excluded osteoporosis, tuberculosis, and diseases that could have potentially affected bone quality. The knee specimens were divided into a control group (intact tibia) ( n=4) and 6 groups of tibial plateau Hoffa fracture malunion model: 3 vertical malunion groups (groups V1, V2, and V3, with a vertical displacement of 1, 2, and 3 mm, respectively, n=4) and 3 separation malunion groups (groups S3, S5, and S7, with a separation displacement of 3, 5, and 7 mm, respectively), with half males and half females in each group. After a 600N vertical load was applied at passive knee flexions at 0°, 30°, 60°, 90°, and 120°, the stress levels in the medial and lateral compartments of the knee joint were measured using pressure-sensitive films. Results:Under a vertical load of 600 N, when the knee joint was in a neutral position (flexion of 0°), the differences in the medial and lateral tibial plateau stress values were not statistically significant between the malunion models groups and the control group ( P>0.05). When the knee flexion increased to 30°, the medial tibial plateau stress in the V3 and S7 groups was significantly greater than that in the control group ( P<0.05). At a knee flexion of 60°, the medial plateau stress was significantly greater in the V3, S5 and S7 groups than that in the control group, and the differences were significantly greater than the comparisons at a knee flexion of 30° (all P<0.05). When the knee flexion was 90°, the medial plateau stress in the V2, V3, S5 and S7 groups was significantly greater than that in the control group ( P<0.05), but the lateral tibial plateau stress in the V3 group was significantly smaller than that in the control group ( P<0.05). When the knee flexion was further increased to 120°, the differences in the medial and lateral plateau stress values were statistically significant between all the malunion groups and the control group ( P<0.05), and the differences significantly greater than the comparisons at a knee flexion of 90° (all P<0.05). Under a vertical load of 600 N, the differences in the stresses on the medial and lateral plateaus were not statistically significant between the control group and all the malunion groups at a knee flexion of 0° ( P>0.05). When the knee flexion increased to 30°, the difference between the medial and lateral stresses was not statistically significant in the control group ( P>0.05), but was statistically significant in the V3 and S7 groups ( P<0.05). When the knee flexion reached 60°, 90°, and 120°, the differences between the medial and lateral tibial plateau stresses in all the groups were statistically significant ( P<0.05). Conclusions:The peak knee stresses after malunion of Hoffa fracture of the tibial plateau correlate with the severity of malunion and knee flexion angles. The mechanical properties are not significantly different between a mild malunion knee and a normal knee, but a significant displacement (vertical displacement >2 mm and separation displacement ≥5 mm) may increase the peak knee stresses to increase the risk of knee osteoarthritis. When the severity of malunion is certain, an increase in knee flexion angle increases the difference in the peak stress between the medial and lateral tibial plateaus, thus increasing the risk of knee osteoarthritis.