Targeted therapies for lupus nephritis: Current perspectives and future directions / 中华医学杂志(英文版)

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Pulmonary Nodules / 中国实验方剂学杂志

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics / 药学学报

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back / 中国修复重建外科杂志

OBJECTIVE@#To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.@*METHODS@#Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.@*RESULTS@#All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.@*CONCLUSION@#The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.

Comparison of Quality of Life of the Patients Three Months after Uniportal and Multiportal Thoracoscopic Lobectomy / 中国肺癌杂志

BACKGROUND@#The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy.@*METHODS@#Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes.@*RESULTS@#A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group.@*CONCLUSIONS@#Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.

Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Investigation of Antigen and Gene Frequency of Kell(K) and Rh(D) Blood Groups in Xinjiang / 中国实验血液学杂志

OBJECTIVE@#To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area.@*METHODS@#A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed.@*RESULTS@#The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01).@*CONCLUSION@#The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.

Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring / 中国骨伤

OBJECTIVE@#To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy.@*METHODS@#From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria).@*RESULTS@#All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05).@*CONCLUSION@#The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Consistency between iodine-unstained area and tumor pathological size of endoscopic submucosal dissection specimen in superficial esophageal cancer / 中华消化内镜杂志

Objective:To investigate the consistency between the iodine-unstained area and the pathological size of endoscopic submucosal dissection (ESD) specimens of superficial esophageal cancer.Methods:A retrospective study was performed on data of 32 patients with superficial esophageal cancer who accepted ESD from May 2019 to April 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The maximum transverse diameter and maximum longitudinal diameter of the iodine-unstained area were compared with the tumor pathological area. A size difference no more than 0.5 cm was considered as conformity, any difference between 0.5 and 1.0 cm was considered as non-conformity, and any difference no less than 1.0 cm was considered as serious non-conformity. At the same time, pink sign after spraying Lugo solution and the consistency of pink sign area with the iodine free area were observed.Results:A total of 32 patients with 33 lesions were enrolled in this study, including 23 males and 9 females and the age of the patients was 59.5±7.3 years. There were 19 (57.6%) lesions whose size of iodine-unstained area was consistent with the tumor pathological area. These 19 lesions were all positive for the pink sign, and the pink sign area overlapped with the iodine-unstained area. In addition, 4 (12.1%) iodine-unstained areas of the lesions did not match the size of the pathological area, and 10 (30.3%) iodine-unstained areas of the lesions were seriously inconsistent with the size of the pathological area. These 14 (42.4%) lesions were all positive for pink sign, and the pink sign area was significantly smaller than the iodine-unstained area. Among the 14 discordant lesions, 2 lesions underwent ESD according to the iodine-unstained area, which resulted in excessive resection and postoperative stenosis.Conclusion:Determining the extent of superficial esophageal cancer by iodine-unstained areas before ESD may lead to excessive resection of the lesions, which is related to the fact that the iodine-unstained areas of the lesions are sometimes significantly larger than the pink sign areas. Therefore, in order to achieve precise treatment, endoscopists can choose the iodine-unstained area with positive pink sign as the first choice for resection.

Biologics in treatment of lupus nephritis / 中华肾脏病杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes damage to multiple vital tissues and target organs, and lupus nephritis (LN) is a serious complication of SLE involving the kidneys. The use of glucocorticoids and immunosuppressants has been dominant in the treatment strategy of LN, while their adverse effects have also raised concerns. In recent years, the development and use of biologics have provided new ideas for the treatment of LN and have also achieved positive efficacy in several clinical trials in SLE and LN. Biologics can be divided into monoclonal antibodies and recombinant proteins, which exert therapeutic effects on SLE and LN through a variety of mechanisms at the cellular-molecular level. In this article, we review recent research advances in the treatment of SLE and LN from the perspective of the different mechanisms of action of biologics.

Efficacy and safety of belimumab combined with standard regimen in the treatment of active lupus nephritis / 中华肾脏病杂志

Objective:To evaluate the efficacy and safety of belimumab combined with standard regimen in the treatment of active lupus nephritis (LN).Methods:It was a single-center, pre - and post-control retrospective study. The Data of active LN patients treated with belimumab combined with standard regimen in the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from June 1, 2020 to June 30, 2022 were collected for analyzing the renal response rate and adverse reactions after belimumab treatment.Results:A total of 17 patients were included, including 14 females (82.35%). The age of the first medication was (26.06±2.64) years old, the median time of illness before the use of belimumab was 24.00 (8.50, 48.50) months, and the recurrence times before the use of belimumab was (1.24±1.03) times. All the 17 patients underwent renal biopsy. The main pathological types were type IV in 11 cases (11/17), type Ⅲ+V in 2 cases (2/17), type IV+V in 3 cases (3/17), and type V in 1 case (1/17). The dose of glucocorticoids was (22.95±8.30) mg/d in 1 year before belimumab administration. In 12 patients with LN who completed 24 weeks of belimumab treatment plan, the 24-hour urinary protein showed a downward trend, and there was a statistically significant difference compared with the baseline at 24 week [0.49 (0.15, 2.19) g vs. 2.83 (1.14, 4.11) g, Z=-2.100, P=0.036]. Compared with the baseline, serum albumin at 24 week increased by 29.36%, with statistically significant difference [(34.50±3.34) g/L vs. (26.67±5.75) g/L, t=-3.840, P=0.030]. The systemic lupus erythematosus disease activity index-2K score continued to decline, with statistically significant difference compared with baseline at 24 week (5.00±3.02 vs. 12.00±2.82, t=6.163, P<0.001). The lymphocyte count increased, and the difference was statistically significant compared with the baseline at 24 week [0.72(0.28, 2.39)×10 9/L vs. 0.30(0.19,0.34)×10 9/L, Z=-2.073, P=0.038]. There was a statistically significant difference between the glucocorticoids dosage at 24 week and the average glucocorticoids dosage 1 year before treatment [(11.25±6.35) mg/d vs. (22.60±9.75) mg/d, t=4.225, P=0.003]. After observation of belimumab for (38.13±22.93) weeks, patients had a complete response rate of 64.71% (11/17), a partial response rate of 17.65% (3/17), and an overall response rate of 82.35% (14/17). Relapse occurred in 1 case.No infusion-related reactions occurred in 17 patients. During the treatment, a total of 5 adverse events occurred, including 2 cases of pulmonary infection, 1 case each of sepsis, upper respiratory tract infection, and cytomegalovirus infection, which all improved after treatment and the subsequent treatment was not affected. Conclusion:Belimumab combined with standard regimen can improve the response rate of LN, reduce the recurrence rate, reduce the dosage of glucocorticoids, and control the overall adverse events with good prognosis.

Analysis of eye movement characteristics in newly diagnosed drug-naive Parkinson′s disease / 中华神经科杂志

Objective:To explore eye movement characteristics in newly diagnosed, drug-naive Parkinson′s disease (PD) patients and their correlation with motor and non-motor symptoms.Methods:Seventy-five newly diagnosed, drug-naive PD patients and 46 healthy controls (HCs) were included in this cross-sectional study. Patients were recruited from the Department of Neurology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from November 2017 to December 2021, while HCs were recruited from the local community during the same period. For PD patients, motor severity was measured with the modified Hoehn and Yahr stage, Movement Disorder Society Unified Parkinson′s Disease Rating Scale part Ⅲ and the Freezing of Gait questionnaire. Non-motor symptoms were evaluated by serial scales such as Non-Motor Symptoms Questionnaire, 16-item odor identification test from Sniffin Sticks, 17-item Hamilton Rating Scale for Depression, Chinese version of Mini-Mental State Examination, Montreal Cognitive Assessment Basic and REM Behavior Disorder Screening Questionnaire. All subjects underwent oculomotor test including pro-saccade task and smooth pursuit eye movement (SPEM) task in the horizontal direction via videonystagmography. Visually guided saccade latency, saccadic accuracy and gain in SPEM at three frequencies (0.1, 0.2, 0.4 Hz) of the horizontal axis were compared between the 2 groups. The association between key oculomotor parameters and clinical phenotypes was explored in PD patients. The receiver operating characteristic (ROC) analyses of eye movement parameters as independent factors were also performed for detecting PD from HCs, then combining the saccadic latency, saccadic accuracy and the most significant SPEM gain (0.4 Hz) as the model to distinguish PD from HCs.Results:Relative to HCs, newly diagnosed, drug-naive PD patients showed prolonged saccadic latency [(210.4±41.3) ms vs (191.3±18.9) ms, t=-3.445, P=0.001] and decreased saccadic accuracy (88.4%±6.8% vs 92.2%±6.1%, t=3.064, P=0.003). SPEM gain in PD was uniformly reduced at each frequency(0.1 Hz: 0.68±0.15 vs 0.74±0.14, t=2.261, P=0.026; 0.2 Hz: 0.72±0.16 vs 0.79±0.16, t=2.704, P=0.008; 0.4 Hz: 0.67±0.19 vs 0.78±0.19, t=2.937, P=0.004). The ROC analyses of saccade latency, saccadic accuracy and gain in SPEM at 0.1, 0.2, 0.4 Hz as independent factors for detecting PD from HCs showed that the area under the curve (AUC) of each parameter was lower than 0.7: the AUC of saccade latency was 0.641 ( P=0.010), the AUC of saccadic accuracy was 0.681 ( P=0.001), the AUC of gain in SPEM at 0.1 Hz was 0.616 ( P=0.032), at 0.2 Hz was 0.652 ( P=0.005), at 0.4 Hz was 0.660 ( P=0.003). Combining the saccadic latency, saccadic accuracy and the most significant SPEM gain (0.4 Hz) revealed that the model could significantly distinguish PD from HCs with an 80.4% sensitivity and a 73.3% specificity (AUC=0.780, P<0.001). Prolonged saccadic latency was correlated with long disease duration ( β=0.334, 95% CI 0.014-0.654, P=0.041), whereas decreased SPEM gain was associated with severe motor symptoms in newly diagnosed drug-naive PD patients (0.1 Hz: β=-0.004, 95% CI -0.008--0.001, P=0.036; 0.4 Hz: β=-0.006, 95% CI -0.011--0.001, P=0.012). Conclusions:Ocular movements are impaired in newly diagnosed, drug-naive PD patients. These changes could be indicators for disease progression in PD.

Role of different melanocyte populations in the reconstitution of pigmented hair follicles / 中华皮肤科杂志

Objective:To observe whether hair follicle cells from mice of different species can integrate to generate new pigmented hair follicles, and to explore the role of different melanocyte populations in pigmented hair follicle reconstruction in mice.Methods:The epidermal cell population, hair follicle epithelial cell population and dermal cell population were isolated from the skin of fetal or neonatal C57BL/6J and BALB/C mice, and epidermal melanocytes were obtained by culture and purification of the epidermal cell population. The experiments were divided into 3 parts: (1) hair follicle reconstruction experiment in neonatal C57BL/6J mice, which included 2 groups: epidermal cells + hair follicle epithelial cells group and dermal cells group; (2) chimeric hair follicle reconstruction experiment, which included 4 groups: dermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice group, dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group, and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group; (3) pigmented hair follicle reconstruction experiment, which included 3 groups: dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group, dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group, and dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group. Different cells were implanted into dorsal skin fold chambers of the nude mice, and there were 4 mice in each group. At weeks 4 and 8 after inoculation, hair follicle reconstruction was assessed by gross observation, histological examination and immunofluorescence assay.Results:Among the 8 BALB/C nude mice in the 2 groups in the hair follicle reconstruction experiment, 7 survived and 1 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, no hair growth was observed in the epidermal cells + hair follicle epithelial cells group (3 mice) , while normal hair grew out in the dermal cells group (4 mice) mixed with epithelial components. Among the 16 BALB/C nude mice in the 4 groups in the chimeric hair follicle reconstruction experiment, 14 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + dermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of fetal BALB/C mice + dermal cells of fetal C57BL/6J mice group (3 mice) . Among the 12 BALB/C nude mice in the 3 groups in the pigmented hair follicle reconstruction experiment, 10 survived and 2 died of wound infections on week 4 after inoculation; at weeks 4 and 8 after inoculation, only white hair grew out in the dermal cells of neonatal BALB/C mice + cultured C57BL/6J epidermal melanocytes group (3 mice) , and no hair follicle melanocytes were observed by immunofluorescence assay, while brown-grey hair grew well in the dermal cells of neonatal BALB/C mice + epidermal cells of neonatal C57BL/6J mice group (4 mice) , and dermal cells of neonatal BALB/C mice + hair follicle epithelial cells of neonatal C57BL/6J mice group (3 mice) .Conclusions:The interaction between mesenchymal cells and hair follicle epithelial cells is a necessary condition for hair follicle reconstruction. The hair follicle cells from different species of mice can integrate to generate new pigmented hair follicles. Both hair follicle melanocytes and epidermal melanocytes can participate in the formation of pigmented hair follicles, but differentiated melanocytes have no such ability.

Role of PIAS-regulated SUMOylation of PPARγ in endogenous protective mechanism against endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of small ubiquitin-associated modifier (SUMO) E3 ligase (PIAS)-regulated SUMOylation of peroxisome proliferator-activated receptor γ (PPARγ) in the endogenous protective mechanism against endotoxin-induced acute lung injury (ALI) in mice.Methods:Experiment Ⅰ Twenty-four clean-grade wild type male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ PPARγ inducer TZD group (ALI+ T group) and ALI+ TZD+ SUMOylation inhibitor anacardic acid group (ALI+ T+ A group). Lipopolysaccharide (LPS) 15 mg/kg was injected into the tail vein to develop the ALI model. In ALI+ T+ A group, anacardic acid 5 mg/kg was intraperitoneally injected at 1 h before LPS administration. In ALI+ T group and ALI+ T+ A group, TZD 50 mg/kg was intraperitoneally injected at 30 min before LPS administration. The mice were sacrificed at 12 h after LPS administration, and the lung tissues were obtained to examine the pathological changes which were scored and to determine the wet/dry (W/D) weight ratio, and expression of PIAS1, PIAS2, PIAS3 and PIASy protein and mRNA (by Western blot or polymerase chain reaction). Experiment Ⅱ Mouse alveolar macrophages (MH-S cells) were cultured in vitro and divided into 4 groups ( n=5 each) using a random number table method: control group (C group), LPS group, LPS+ PIAS2 siRNA group (L+ P group) and LPS+ Con siRNA group (L+ C group). Cells were routinely cultured in group C. Cells were stimulated with 10 μg/ml LPS to develop the model of endotoxin challenge. PIAS2 siRNA 50 nmol/L and Con siRNA 50 nmol/L were transfected at 48 h before LPS was added in L+ P group and L+ C group, respectively. The cells were collected at 24 h of incubation with LPS to determine the cell viability, levels of M1 and M2 alveolar macrophages (by flow cytometry), expression of PIAS2 and PPARγ (by Western blot), co-expression of PPARγ-SUMO1 (by immunoprecipitation) and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) mRNA (by polymerase chain reaction). The ratio of M1/M2 was calculated. Results:Experiment Ⅰ Compared with C group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was up-regulated in the other three groups ( P<0.05). Compared with ALI group, the lung injury scores and W/D ratio were significantly decreased, and the expression of PIAS2 protein and mRNA was up-regulated in ALI+ T group and ALI+ T+ A group ( P<0.05). Compared with ALI+ T group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was down-regulated in ALI+ T+ A group ( P<0.05). There was no significant difference in the expression of PIAS1, PIAS3 and PIASy protein and mRNA in lung tissues among the four groups ( P>0.05). Experiment Ⅱ Compared with C group, the cell viability was significantly decreased, the expression of PPARγ and co-expression of PPARγ-SUMO1 was up-regulated, the levels of M1 and M2 macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was up-regulated, and the expression of IL-10 mRNA was down-regulated in the other three groups, and PIAS2 expression was significantly up-regulated in L group and L+ C group ( P<0.05). Compared with L group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and PPARγ-SUMO1 co-expression were down-regulated, the M1 macrophage level and M1/M2 ratio were increased, TNF-α mRNA expression was up-regulated, and the expression of IL-10 mRNA was down-regulated in L+ P group ( P<0.05), and no significant change was found in the parameters mentioned above in L+ C group ( P>0.05). Compared with L+ C group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and co-expression of PPARγ-SUMO1 were down-regulated, the level of M1 alveolar macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was down-regulated, and the expression of IL-10 mRNA was up-regulated in L+ P group ( P<0.05). Conclusions:PIAS2-regulated SUMOylation of PPARγ is the endogenous protective mechanism against endotoxin-induced ALI in mice, which may be related to inhibition of macrophage polarization into M1 type and alleviation of inflammatory responses.

Role of succinate dehydrogenase in hypoxic postconditioning-induced reduction of hypoxia-reoxygenation injury in myocardial cells of rats and the relationship with mito-K ATP / 中华麻醉学杂志

Objective:To evaluate the role of succinate dehydrogenase (SDH) in hypoxic postconditioning (HPC)-induced reduction of hypoxia-reoxygenation (H/R) injury in myocardial cells of rats and the relationship with mitochondrial ATP-sensitive potassium channels (mito-K ATP). Methods:Myocardial cells isolated from adult male Sprague-Dawley rats were cultured for 48 h and then divided into 7 groups ( n=24 each) using a random number table method: blank control group (Nor group), H/R group, SDHA-siRNA adenovirus+ H/R group (siRNA+ H/R group), HPC group, SDHA-siRNA adenovirus+ HPC group (siRNA+ HPC group), 5-HD+ HPC group, and SDHA-siRNA adenovirus+ 5-HD+ HPC group (siRNA+ 5-HD+ HPC group). Nor group was continuously cultured for 195 min under normoxic conditions. The H/R injury model was prepared by exposing the cells to hypoxia for 45 min in 5% CO 2 + 1% O 2 + 94% N 2, followed by reoxygenation for 150 min. The HPC method involved three cycles of 5 min reoxygenation/5 min hypoxia at the end of 45 min ischemia before 120 min reoxygenation. The mito-K ATP blocker 5-HD administration method involved adding 5-HD at a final concentration of 100 μmol/L at 30 min of hypoxia. The myocardial cells in each siRNA group were successfully transfected with SDHA-siRNA adenovirus to silence SDHA expression. The cell viability, calcium ion level, SDH activity, ATP content, degree of mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential (MMP) were measured at the end of reoxygenation. Results:Compared with Nor group, the cell viability, ATP content and MMP were significantly decreased, and the degree of mPTP opening, level of calcium ion and activity of SDH were increased in H/R group ( P<0.05). Compared with H/R group, the cell viability, ATP content and MMP were significantly increased, and the degree of mPTP opening, calcium ion level and SDH activity were decreased in siRNA+ H/R group and HPC group ( P<0.05). Compared with HPC group, the cell viability, ATP content and MMP were significantly decreased, and the degree of mPTP opening, calcium ion level and SDH activity were increased in 5-HD+ HPC group ( P<0.05), and the cell viability, ATP content and MMP were significantly increased, and the degree of mPTP opening, calcium ion level and SDH activity were decreased in siRNA+ HPC group ( P<0.05). Compared with siRNA+ HPC group, the cell viability, ATP content and MMP were significantly decreased, the opening degree of mPTP and calcium ion level were increased ( P<0.05), and no significant change was found in the SDH activity in siRNA+ 5-HD+ HPC group ( P>0.05). Compared with 5-HD+ HPC group, the SDH activity was significantly decreased, and no significant change was found in the other parameters in siRNA+ 5-HD+ HPC group ( P>0.05). Conclusions:HPC alleviates H/R injury probably by reducing SDH activity and opening mito-K ATP in myocardial cells of rats.

Characteristics, cellular and molecular mechanisms of renal aging and nutritional intervention strategies / 中华老年医学杂志

Renal aging is a gradual process of degenerative changes in tissue structure and physiological function and is closely related to the occurrence and development of acute kidney injury(AKI)and chronic kidney disease(CKD). The cellular and molecular mechanisms of renal aging mainly include cellular senescence and reduced autophagy, and are regulated by nutritional factors.Promoting reasonable and moderate energy-and protein-restricted diets, strengthening the supervision of food additives and preservatives, cultivating safety awareness of residents, and strictly controlling the daily salt intake are potential nutritional intervention strategies to prevent and delay renal aging.Given the limited number of studies, there is an urgent need to further explore the effectiveness of the above strategies to provide a new evidence-based approach to formulating precise and feasible personalized nutritional intervention programs.

Value of machine learning model based on 18F-FDG PET/CT radiomics features in differential diagnosis between gastric cancer and primary gastric lymphoma / 中华核医学与分子影像杂志

Objective:To investigate the value of machine learning model based on 18F-FDG PET/CT radiomics features in preoperative differential diagnosis of gastric cancer (GC) and primary gastric lymphoma (PGL). Methods:A total of 155 patients with GC (104 males, 51 females; age (59.3±12.8) years) and 82 patients with PGL (40 males, 42 females; age (56.8±14.6) years) who underwent 18F-FDG PET/CT imaging before treatment from January 2012 to December 2020 in Tianjin Medical University Cancer Institute and Hospital were included in this retrospective study. Patients were randomly divided into training set and test set by using Python3.7.1 software. Volumes of interest (VOIs) in PET and CT images were drawn and two-dimensional and three-dimensional radiomics features were extracted. Two machine learning models, including multi-layer perceptron (MLP) and support vector machine (SVM), were established based on CT radiomics features alone, PET radiomics features alone and PET/CT radiomics features to differentiate GC and PGL, respectively. The predictive performance of each model was evaluated by ROC curve analysis. Results:There were 166 patients in training set and 71 patients in test set. Generally, SVM machine learning model based on PET/CT radiomics features showed a trend to be superior to MLP machine learning model in the differential diagnosis of GC and PGL (PET-SVM: AUC=0.88, 95% CI: 0.83-0.94); PET/CT-MLP: AUC=0.80, 95% CI: 0.73-0.87; z=1.15, P=0.337). The AUC of PET/CT-SVM machine learning model was significantly higher than that of CT-SVM machine learning model (CT-SVM: AUC=0.74, 95% CI: 0.67-0.81; z=2.28, P=0.022). Conclusion:Machine learning model based on 18F-FDG PET/CT radiomics features is expected to be a non-invasive, effective tool for preoperative differential diagnosis of GC and PGL.

Predictive value of 18F-FDG PET/CT radiomic fusion features combined with XGBoost model for HER2 expression status in breast cancer / 中华核医学与分子影像杂志

Objective:To evaluate the value of radiomic fusion features combined with extreme gradient boosting (XGBoost) machine learning models based on 18F-FDG PET/CT images in the prediction of human epidermal growth factor receptor 2 (HER2) expression status in breast cancer. Methods:18F-FDG PET/CT images of 210 patients with primary breast cancer (all females; age 52(46, 60) years; 95 HER2-positive and 115 HER2-negative) in Tianjin Medical University Cancer Institute and Hospital between January 2012 and December 2019 were retrospectively analyzed. About 70% of the HER2-positive and HER2-negative groups were randomly selected using Python 3.7.1 software as a training set ( n=147; 67 HER2-positive and 80 HER2-negative, age: 52(46, 60) years vs 55(45, 62) years) and 30% as a test set ( n=63; 28 HER2-positive and 35 HER2-negative, age: 54(43, 65) years vs 52(45, 61) years). After tumor segmentation on CT and PET images being finished, CT and PET radiomic features were extracted respectively. PET/CT fusion features (including PET/CT splicing features and PET/CT mean features) were obtained through post-processing. The support vector machine (SVM) model and XGBoost model were established. The selected features were input to predict the expression status of HER2 in primary breast cancer lesions, and the prediction efficiency of the model was evaluated by ROC curve. The Delong test was used to compare the predictive effectiveness of different models and radiomic features, and the calibration curve of the machine learning model with the highest prediction efficiency was plotted. Results:Compared with SVM model, XGBoost model had better prediction performance ( z values: 2.26-3.54, P values: 0.016-0.040) when four kinds of radiomic features (CT features, PET features, PET/CT splicing features and PET/CT mean features) were input. ROC curve analysis showed that PET/CT mean features with XGBoost machine learning model had the best performance in predicting the expression status of HER2, and the maximum AUC was 0.83 (95% CI: 0.73-0.93), which was superior to CT features (0.75(95% CI: 0.63-0.88); z=3.57, P=0.027), PET features (0.73(95% CI: 0.60-0.86); z=2.64, P=0.034) and PET/CT splicing features (0.74(95% CI: 0.60-0.87); z=2.49, P=0.037). Conclusion:XGBoost machine learning model based on PET/CT radiomics fusion features is expected to predict HER2 expression status in patients with breast cancer.

Evaluation and analysis on diagnostic criteria for common occupational radiation-induced diseases among radiation workers in some provinces and cities of China / 中华放射医学与防护杂志

Objective:To investigate the application of diagnostic criteria for common occupational radiation-induced diseases to radiation workers, in order to provide a basis for the revision, publicity and standardization of the standards.Methods:Radiation workers were selected from 1 city, 7 provinces and 1 corporation by using cluster random sampling method from January 2021 to May 2021. Awareness of the criteria and the effects of ionizing radiation, and the suggestions for diagnostic works were investigated and analyzed.Results:A total of 2 839 radiation workers were investigated. There were differences in the awareness of different diagnostic criteria, the inclusions in complex diagnostic criteria, the materials required for applying for diagnosis, and the ways of knowing the diagnostic criteria( χ2=416.06, 2 924.14, 83.45, 895.67, 815.94, P<0.001). The correct understanding rates of deterministic effects and stochastic effects were 80.63% and 43.64%, respectively. The acceptance rates in applicable materials were 96.79% for occupational exposure history, 94.72% for occupational health monitoring records and 93.55% for individual monitoring of occupational exposure, respectively. Pre-employment training rate was 80.20%, on-job training rate was 81.19%, and untrained rate was 3.77%. The suggestions to the diagnosis of occupational radiation-induced diseases are to strengthen training, pay attention to individual monitoring, occupational health examination, and strengthen health supervision and law enforcement. Conclusions:Radiation workers have a low awareness rate of certain diagnostic standards and a high awareness rate of diagnostic procedures. Publicity and training of health effects of ionizing radiation and diagnostic criteria of occupational radiation-induced diseases should be strengthened. Diagnostic procedure should be optimized.