Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs / 中国药理学通报

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine / 中国结合医学杂志

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.

Design of variable stiffness insole based on diabetics plantar pressure during gait period / 中国康复理论与实践

ObjectiveTo analyze the characteristics of plantar pressure of diabetic patients during gait cycle, and to design a offloading insole with variable stiffness. MethodsThe plantar pressure experiment was carried out and a database including 157 subjects was established. The differences of plantar pressure distribution were analyzed among diabetic patients with and without peripheral neuropathy, and healthy people. The insole pressure area was divided, and porous units were filled in different insole areas according to the pressure gradient. The fed-calf-insole finite element model of diabetic patients was constructed. The simulation analysis of different insole schemes was carried out under the conditions of push-off, footheel-strike and dynamic neutrality posture, and to explore the most reasonable insole stiffness design. ResultsCompared with the healthy group, the percentage of peak pressure and high pressure in the left and right heel areas of diabetic neuropathy patients showed a decreasing trend, in which the left peak pressure was significantly reduced by 11% (P = 0.026) and the percentage of high pressure was significantly reduced by 9.8% (P = 0.02). When the porous elements of 2.5 MPa and 1.9 MPa were used in the high pressure area of the insole metatarsal and high pressure area of the heel, the peak plantar pressure of footheel-strike, dynamic neutral and push-off was reduced by 42.4%, 27.4% and 26.4%, and the peak stress of the soft tissue was reduced by 49.8%, 43.6% and 25.1%, respectively. ConclusionThere is a higher risk of ulcer in the metatarsal region than in the heel region for diabetic patients. The variable stiffness insoles based on the optimization of plantar pressure and internal stress under multi-posture can effectively reduce the peak pressure of plantar and peak stress of soft tissue during walking, which provides a reference for the design of variable stiffness insoles.

Effect of antidepressants on thyroid hormone level in adolescent depression with suicidal ideation / 上海预防医学

ObjectiveTo compare the differences in thyroid hormone levels between adolescents with and without suicidal ideation， and to explore the association between thyroid hormone/suicidal ideation and the antidepressant treatment. MethodsA total of 100 patients were divided into non-suicidal ideation group and suicidal ideation group according to the SIOSS. The levels of thyroid-stimulating hormone （TSH）， triiodothyronine （T3）， thyroxine （T4）， free triiodothyronine （FT3） and free thyroxine （FT4） were compared between the two groups as well as their changes after 6 weeks of antidepressant treatment. ResultsThe levels of FT3， FT4 and T4 in the non-suicidal ideation group were higher than those in the suicidal ideation group. After 6 weeks of antidepressant treatment， the levels of FT3， FT4 and T4 in the suicide ideation group were higher than those before the treatment. The FT3 level in the male non-suicidal ideation group was higher than that in the suicidal ideation group. The levels of FT4 and T4 in the female non-suicidal ideation group were higher than those in the suicidal ideation group （all P<0.05） ConclusionThere are differences in thyroid hormone levels between adolescents with and without suicidal ideation （both with first-episode depression）， and patients with suicidal ideation have significant changes after treatment with antidepressants.

Clinical observation of contralateral needling combined with Maitland ankle mobilization for chronic ankle sprain / 针灸推拿医学（英文版）

Objective: To observe the efficacy of contralateral needling combined with Maitland ankle mobilization in the treatment of chronic ankle sprain.Methods: A total of 106 patients with chronic ankle sprain were included in the study. They were numbered according to their order of visit, with odd numbers assigned to the control group and even numbers assigned to the observation group, with 53 cases in each group. Patients in the control group were treated with Maitland ankle mobilization, while those in the observation group were given additional contralateral needling treatment. After treatment, we observed the indicators including, ankle circumference, range of motion (ROM) of dorsiflexion, ROM of plantar flexion, thickness of ankle ligaments, and the changes in Baird-Jackson ankle score, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS) score to compare the efficacy between the two groups. Results: After treatment, the total effective rate of the observation group was 94.3％ and was significantly higher than that of the control group (81.1％), indicating statistical significance (P<0.05). After treatment, the ankle circumference of both groups decreased, and the ROM of dorsiflexion and the ROM of plantar flexion increased (P<0.05). The changes in the observation group were more significant, indicating inter-group statistical significance (P<0.05). After treatment, the thickness of the anterior talofibular ligament, calcaneofibular ligament, and posterior talofibular ligament, as well as the VAS scores decreased in both groups; the changes in the observation group were more significant, indicating inter-group statistical significance (P<0.05). After treatment, the Baird-Jackson ankle score and the AOFAS ankle- hindfoot score increased in both groups, and the scores in the observation group were higher than those in the control group, indicating inter-group statistical significance (P<0.05). Conclusion: The efficacy of contralateral needling combined with Maitland ankle mobilization in the treatment of chronic ankle sprain is superior to that of Maitland ankle mobilization alone.

Bone turnover markers, hip bone geometry parameters and metabolic syndrome in community overweight postmenopausal women / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.

Impact of insulin injection induced lipohypertrophy on multidimensional glucose variability in patients with type 1 diabetes mellitus / 中华内分泌代谢杂志

Objective:This study aimed to investigate the effect of lipohypertrophy induced by insulin injection on blood glucose fluctuation in patients with type 1 diabetes mellitus.Methods:A total of 80 patients with type 1 diabetes mellitus were recruited between June 2021 and December 2021 from the First Affiliated Hospital of Nanjing Medical University. And these patients all received insulin injection more than six months. Lipohypertrophy was assessed by ultrasound scanning, and blood glucose fluctuation was evaluated using the flash glucose monitoring system(FGM). Univariate analysis and multivariate linear regression were used to analyze the relationship of lipohypertrophy and and core indicators of blood glucose fluctuation.Results:Compared with patients without lipohypertrophy, patients with lipohypertrophy had higher mean amplitude of glycemic excursions(MAGE), coefficient of variation(CV), mean of daily differences(MODD), standard deviation(SD) of blood glucose, time above range(TAR), and high blood glucose index(HBGI; all P<0.05), while time in range(TIR) of glucose markedly become lower( P<0.01). Moreover, multivariate linear regression analysis showed that lipohypertrophy detected by ultrasound was an independent influencing factor of TIR( β=-9.423, P=0.032), MAGE( β=1.114, P=0.039), CV( β=4.304, P=0.041), MODD( β=0.717, P=0.046) after adjusting for age at diagnosis, duration of insulin injection, fasting C-peptide, and daily dose of insulin per unit weight. Conclusion:Lipohypertrophy increases glycemic variability and imposes negative impact on glycemic control rate in patients type 1 diabetes mellitus.

The clinical characteristics and prognostic value of PSA dynamic features in patients with metastatic castration resistant prostate cancer received abiraterone acetate / 中华泌尿外科杂志

Objective:To analyze the clinical characteristics and prognostic value of prostate-specific antigen (PSA) dynamic features in patients with metastatic castration resistant prostate cancer (mCRPC) received abiraterone acetate (AA) therapy.Methods:The data of 89 patients with mCRPC who received AA therapy from January 2017 to June 2021 in Shanghai Tongji Hospital were retrospectively reviewed. The age of patients was (75.7 ± 8.3) years old, median PSA before AA was 56.88 (19.31, 143.75) ng/ml. The PSA dynamic features included PSA nadir (PSAN) and PSAN time. PSAN was defined as the lowest value of PSA after treatment, and PSAN time was defined as time to PSAN after AA treatment. PSAN was divided into 3 groups: PSAN1 (<0.1 ng/ml), PSAN2 (0.1- 4.0 ng/ml) and PSAN3 (>4.0 ng/ml) groups. PSA response was defined as a maximum PSA decline rate ≥50%, and no PSA decline after treatment was defined as primary resistance. Cox regressions adjusted to clinical factors were performed to evaluate the influence of PSA dynamic features on patients' radiographic progression-free survival (rPFS) and overall survival (OS). Log-rank test was used to evaluate the survival time of patients in different PSAN groups. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were performed to analyze the predictive value of PSA dynamic features on survival outcomes of patients.Results:The follow-up time was 17 (12, 23) months, and 75 (84.3%) patients showed PSA responses. The median PSAN was 1.82 (0.01, 11.70) ng/ml, median PSAN time was 5.0(3.0, 9.5)months. Multivariate Cox regression indicated that PSAN was an independent risk factor for rPFS ( PSAN2: HR=5.308, P=0.017; PSAN3: HR=13.209, P<0.001), and PSAN time ≥ 5 months( HR=0.309, P<0.001)was an independent protective factor for rPFS. Also, the PSAN3 was an independent risk factor for OS( HR=9.459, P=0.048). Log-rank test indicated that the rPFS of PSAN1 group (median not reached) was significantly longer than PSAN2 [median 13.0(95% CI 8.2-17.8) months, P=0.001] and PSAN3 [8.0 (95% CI 4.1-11.9) months, P<0.001] groups. ROC curve and AUC showed that PSAN had a higher predictive value in rPFS outcomes compared with T stage, metastatic disease volume, and Eastern Cooperative Oncology Group (ECOG) score (0.82 vs. 0.69, 0.68, 0.53, P<0.05). PSAN had a higher predictive value in OS outcomes than metastatic disease volume and ECOG(0.83 vs. 0.63, 0.58, P<0.05). Conclusions:Lower PSAN needs longer PSAN time. PSAN is an independent risk factor for rPFS and OS, and PSAN time is an independent protective factor for rPFS.

Hepatic pedicle-first approach for laparoscopic anatomical hepatectomy for the central segments: 19 cases report / 中华肝胆外科杂志

Objective:To assess the safety and feasibility of hepatic pedicle-first approach laparoscopic anatomical hepatectomy for central segments.Methods:The clinical data of 19 patients with hepatocellular carcinoma who underwent hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from September 2020 to January 2023 were retrospectively analyzed. In this procedure, hepatic pedicles of the central segments were divided first to delineate the ischemic demarcation and guide the liver parenchymal transection. The methods of operation, operation time, intraoperative blood loss, postoperative complications and hospital-stay were analyzed.Results:Hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments was successfully performed in all patients, including 5 cases of segment Ⅳ, 2 cases of segment Ⅳ+ Ⅷ, 3 cases of segment Ⅳ+ ventral segment Ⅷ, 3 cases of segment Ⅳa+ Ⅴ+ Ⅷ and 6 cases of segment Ⅴ+ Ⅷ. The mean operation time, intraoperative blood loss and postoperative hospital stay was (253.1±86.1) min, [ M( Q1, Q3)] 100.0(100.0, 250.0) ml, and (5.1±1.2) d respectively. There was no intraoperative blood transfusion and postoperative complications. Conclusion:Hepatic pedicle-first approach can help delineate the segemental demarcation in laparoscopic anatomical hepatectomy for the central segments, which is technically feasible and worth more practice.

Machine learning based on automated breast volume scanner radiomics for differential diagnosis of benign and malignant BI-RADS 4 lesions / 中华超声影像学杂志

Objective:To evaluate the performance of machine learning (ML) based on automated breast volume scanner (ABVS) radiomics in distinguishing benign and malignant BI-RADS 4 lesions.Methods:Between May to December 2020, patients with BI-RADS 4 lesions from the Affiliated Hospital of Southwest Medical University (Center 1) and Guangdong Provincial Hospital of Traditional Chinese Medicine (Center 2) were prospectively collected and divided into training cohort (Center 1) and external validation cohort (Center 2). The radiomics features of BI-RADS 4 lesions were extracted from the axial, sagittal and coronal ABVS images by MaZda software. In the training cohort, 7 feature selection methods and thirteen ML algorithms were combined in pairs to construct different ML models, and the 6 models with the best performance were verified in the external validation cohort to determine the final ML model. Finally, the diagnostic performance and confidence (5-point scale) of radiologists (R1, R2 and R3, with 3, 6 and 10 years of experience, respectively) with or without the model were evaluated.Results:①A total of 251 BI-RADS 4 lesions were enrolled, including 178 lesions (91 benign, 87 malignant) in the training cohort and 73 lesions (44 benign, 29 malignant) in the external validation cases. ②In the training cohort, the 6 ML models (DNN-RFE, AdaBoost-RFE, LR-RFE, LDA-RFE, Bagging-RFE and SVM-RFE) had the best diagnostic performance, and their AUCs were 0.972, 0.969, 0.968, 0.968, 0.967 and 0.962, respectively. ③In the external validation cohort, the DNN-RFE still had the best performance with the AUC, accuracy, sensitivity, specificity, PPV and NPV were 0.886, 0.836, 0.934, 0.776, 86.8% and 82.5%, respectively. ④Before model assistance, R1 had the worst diagnostic performance with the accuracy, sensitivity, specificity, PPV and NPV were 0.680, 0.750, 0.640, 57% and 81%, respectively. After model assistance, the diagnostic performance of R1 was significantly improved ( P=0.039), and its diagnostic sensitivity, specificity, accuracy, PPV and NPV improved to 0.730, 0.810, 0.930, 68% and 94%; while the improvement of R2 and R3 were not significantly ( P=0.811, 0.752). Meanwhile, the overall diagnostic confidence of the 3 radiologists increased from 2.8 to 3.3 ( P<0.001). Conclusions:The performance of ML based on ABVS radiomics in distinguishing between benign and malignant BI-RADS 4 lesions is good, which may improve the diagnostic performance of inexperienced radiologists and enhance diagnostic confidence.

Distal tibial spiral fracture and ankle injury / 中华创伤骨科杂志

Objective:To characterize the injury to the ipsilateral ankle joint after low energy spiral fracture of the distal tibia.Methods:A retrospective study was conducted to analyze the 80 patients with distal tibial spiral fracture who had been treated at Department of Traumatic Orthopedics, Affiliated Hospital of Jining Medical University from March 2010 to March 2021. There were 61 males and 19 females with an age of (43.5±12.5) years. Their mean follow-up time was 67.0 (38.5, 90.0) months. All patients underwent preoperative X-ray examination, 64 ones preoperative CT examination, and 30 ones preoperative MRI examination. Of the 80 patients, 3 received conservative treatment with plaster external fixation, 3 closed reduction and intramedullary nail fixation, and 74 plate fixation. Statistically analyzed were incidence of posterior malleolus fracture, characteristics of posterior malleolus fracture lines, normal matching rate of the ipsilateral ankle joint, positive rate of intraoperative Cotton test or stress external rotation test of ipsilateral ankle joint, positive rates of passive pronation-external rotation and supination-external rotation stress tests during follow-up, incidences of short-term ankle pain (≤2 years) and medium-long term pain (>2 years) after operation, injuries to the anterior inferior tibiofibular ligament, the deep medial malleolus deltoid ligament and the posterior malleolus, and incidence of ankle injury.Results:The diagnostic rate for posterior malleolus fracture was 16.3% (13/80) on X-ray film, 60.9% (39/64) on CT and 76.7% (23/30) on MRI. 74.5% (35/47) of the posterior malleolus fracture lines opened on the lateral side. The normal matching rate of the ipsilateral ankle joint was 96.3% (77/80). The positive rates of intraoperative Cotton test and stress external rotation test were 34.8% (8/23) and 7.1% (1/14), respectively. The positive rates of passive pronation-external rotation and supination-external rotation stress tests during follow-up were 46.2% (12/26) and 34.6% (9/26). The incidences of postoperative short term (≤2 years) and medium-long term (>2 years) ankle pain were 37.7% (29/77) and 20.8% (16/77). MRI examination showed that the rates of injury to the anterior inferior tibiofibular ligament, deep medial malleolus deltoid ligament and posterior malleolus were 80.0% (24/30), 80.0% (24/30) and 76.7% (23/30). The incidence of ankle injury was 88.8% (71/80).Conclusions:It is highly probable that spiral fracture of the distal tibia is complicated with ipsilateral ankle injury. The medial malleolus, lateral malleolus, and posterior malleolus are prone to the following hidden injuries while the ankle joint is normally matched in the most cases: injury to the deep deltoid ligament in different degrees, rupture of the inferior tibiofibular anterior ligament and posterior malleolus fracture. Therefore, the ankle injury is likely to be missed in diagnosis. The secondary torsion injuries to the pronation-external rotation and supination-external rotation at the leg are likely to cause ipsilateral ankle injury.

Inhibitory effect of long non-coding RNA Neat1 on ultraviolet B-induced pyroptosis of human lens epithelial cells and its mechanism / 中华实验眼科杂志

Objective:To investigate the role of long non-coding RNA nuclear paraspeckle assembly transcript 1 (Neat1) in pyroptosis of ultraviolet B (UVB)-induced human lens epithelial cells (LECs) and to explore the possible mechanism.Methods:The human lens epithelial cell line HLE-B3 was cultured in vitro, and cells at log phase were exposed to ultraviolet B for 0, 2, 4 and 8 hours, respectively.The expression of cysteine aspartic acid-specific protease-1 (caspase-1), a protein related to pyroptosis, was detected by Western blot.The relative expression level of Neat1 in cells after different irradiation durations was determined by real-time quantitative PCR.Cell viability was determined by the cell counting kit-8 (CCK-8) method to screen the optimal irradiation duration for UVB-induced LECs pyroptosis, which was finally determined to be 4 hours.HLE-B3 cells were divided into negative siRNA transfection group, siRNA Neat1 transfection group, negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group, and were transfected with corresponding reagents for 24 hours.The negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group were irradiated with UVB for 4 hours after transfection.The cell viability was detected by the CCK-8 method.The pyroptosis rate was detected by flow cytometry.The expression levels of caspase-1, gasdermin D (GSDMD) and nod-like receptor protein 3 (NLRP3) proteins were detected by Western blot.The concentration of interleukin (IL)-1β was detected by enzyme-linked immunosorbent assay (ELISA). Ultrastructural changes in HLE-B3 cells were observed under a transmission electron microscope. Results:The grayscale of caspase-1 protein bands increased with the extension of irradiation duration.The relative expression levels of caspase-1 protein at 0, 2, 4 and 8 hours of irradiation were 0.05±0.01, 0.25±0.07, 0.51±0.04 and 0.74±0.02, respectively, with a statistically significant overall difference ( F=168.223, P<0.001), and significant differences were found in paired comparisons (all at P<0.05). With prolonged irradiation, the relative expression level of Neat1 mRNA increased and the cell viability decreased, with statistically significant differences in paired comparisons (all at P<0.05). Compared with negative siRNA transfection group, the cell viability was increased in siRNA Neat1 transfection group and decreased in negative siRNA transfection+ irradiation group, with statistically significant differences (both at P<0.01). Compared with negative siRNA transfection+ irradiation group, the cell viability was increased in siRNA Neat1 transfection+ irradiation group, showing a statistically significant difference ( P<0.05). The pyroptosis rate was significantly lower in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group than in negative siRNA transfection+ irradiation group, and the differences were statistically significant (both at P<0.01). The relative expression levels of caspase-1, NLRP3 and GSDMD proteins in negative siRNA transfection+ irradiation group were higher than those in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group and the differences were statistically significant (all at P<0.01). The concentration of IL-1β was significantly higher in negative siRNA transfection+ irradiation group than in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group, and the differences were statistically significant (all at P<0.05). Cell swelling, formed cell membrane pores, vacuolated cells and fuzzy mitochondrial cristae were seen in negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group by transmission electron microscopy.Compared with negative siRNA transfection+ irradiation group, slighter cell swelling, fewer cell membrane pores and lighter mitochondrial swelling were seen in siRNA Neat1 transfection+ irradiation group. Conclusions:Neat1 is involved in human LECs pyroptosis induced by UVB through the classic pyroptosis pathway mediated by caspase-1.Knockdown of Neat1 can inhibit the pyroptosis of human LECs.

Association of Ego-depletion level with glycemic control and quality of life among adolescents with type 1 diabetes / 中国实用护理杂志

Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.

Structural Design and Optimization of Cushioning Insole with Variable Stiffness / 医用生物力学

Objective An X-shaped cushioning insole with variable stiffness was designed to explore its effects on plantar pressure and internal stress of diabetic patients with toe amputation. Methods Based on CT images, the feet-calf finite element model of diabetic patients with toe amputation was established, and the insole was divided into different areas according to distribution characteristics of the planter pressure. The three-dimensional (3D) printed cushioning insole with an X-shaped sandwich structure was designed. The modulus of the sandwichstructure was changed by changing thickness of the sandwich structure panel. For simulation analysis, the divided area was filled with the X-shaped sandwich structure with different modulus. Results The peak plantar pressure of diabetic patients with toe amputation was in calcaneal region, and the combined insoles with 1. 2 mpanel thickness in toe area, 1. 4 mm panel thickness in metatarsal area, 2. 0 mm panel thickness in middle area and 1. 6 mm panel thickness in heel area had the best decompression effect. Compared with bare feet, the peak pressure in heel area of the insole, the peak pressure in phalangeal head area and the stress in plantar softissues were reduced by 40. 18% , 31. 7% , and 50. 44% , respectively. Conclusions The 3D printed insoles with variable stiffness can effectively reduce surface pressure and internal stress of the sole and reduce probability of the 2nd toe amputation

Effect of intravitreal injection of anti-vascular endothelial growth factor agents on systemic concentration of vascular endothelial growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

Survival of Non-small Cell Lung Cancer Patients Treated with Fuzheng Gushe Therapy： A Real World Study / 中国实验方剂学杂志

ObjectiveTo analyze the long-term survival of non-small cell lung cancer （NSCLC） patients treated with Fuzheng Gushe therapy in the real world. MethodA retrospective cohort study was carried out with the NSCLC patients treated with Fuzheng Gushe therapy from January 2014 to December 2018 in Dongzhimen Hospital， Beijing University of Chinese Medicine as the integrated traditional Chinese medicine （TCM） and western medicine cohort. The NSCLC data from January 2011 to December 2015 in the Surveillance， Epidemiology， and End Results （SEER） database were downloaded as the western medicine cohort. The propensity score matching （PSM） was employed to balance the confounding factors between the groups， and comparable samples were obtained from the two groups. The Log-rank test was conducted to compare the overall survival between the groups and the survival curves were established. ResultThe integrated TCM and western medicine cohort and the western medicine cohort included 511 and 5 022 NSCLC patients， respectively. The age， sex， and chemotherapy had no significant differences between the two cohorts， while pathological type， lymph node metastasis （N）， distant metastasis （M）， surgery， and radiotherapy were different between the two cohorts （P<0.05）. After PSM， 122 comparable samples were obtained. The overall survival analysis showed that the total survival of the integrated TCM and western medicine cohort was better than that of the western medicine cohort （P<0.05）. The stratified survival analysis showed that the integrated TCM and western medicine cohort had survival advantages in females， males， the young， and adenocarcinoma， N+， and M+ patients （P<0.05）. ConclusionFuzheng Gushe therapy can significantly improve the overall survival of NSCLC patients， especially in the females， the males， the young， and the patients with adenocarcinoma， lymph node metastasis， and distant metastasis.

Progress on the neuroprotective effects of ginsenoside Rg1 / 药学学报

Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.

Role of Eukaryotic Translation Elongation Factor 1 Family Members in the Tumorigenesis and Progression of Lung Adenocarcinoma / 中国医学科学院学报

Objective To investigate the role and mechanism of eukaryotic translation elongation factor 1(EEF1) family members (EEF1D,EEF1A1,and EEF1A2) in lung adenocarcinoma (LUAD) based on public databases.Methods We examined EEF1 member expression levels in human LUAD samples via The Cancer Genome Atlas in the UCSC Xena browser and the Clinical Proteomic Tumor Analysis Consortium.We analyzed the mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 and their correlations with pathological variables via the Mann-Whitney U test.The Kaplan-Meier curves were established to assess the prognostic values of EEF1D,EEF1A1,and EEF1A2.The single-sample gene set enrichment analysis algorithm was employed to explore the relationship between the expression levels of EEF1 members and tumor immune cell infiltration.Spearman and Pearson correlation analyses were performed to examine the relationship between the expression levels of EEF1 members and those of the genes in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.The immunohistochemical assay was employed to determine the expression levels of EEF1D,EEF1A1,and EEF1A2 in the LUAD tissue (n=75) and paracancer tissue (n=75) samples.Results The mRNA and protein levels of EEF1D,EEF1A1,and EEF1A2 showed significant differences between tumor and paracancer tissues (all P<0.001).The patients with high protein levels of EEF1A1 showed bad prognosis in terms of overall survival (P=0.039),and those with high protein levels of EEF1A2 showed good prognosis in terms of overall survival (P=0.012).The influence of the mRNA level of EEF1D on prognosis was associated with pathological characteristics.The expression levels of EEF1 members were significantly associated with the infiltration of various immune cells and the expression of key molecules in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Conclusion EEF1D,EEF1A1,and EEF1A2 are associated with the progression of LUAD,serving as the candidate prognostic markers for LUAD.

HIV genotypes and molecular transmission networks among MSM with newly reported HIV infections in Dehong Prefecture， Yunnan Province from 2010 to 2019 / 上海预防医学

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.