Effects of immune cells and related cytokines in the pathogenesis and treatment of osteoarthritis / 中国组织工程研究

BACKGROUND:The occurrence and development of osteoarthritis is strongly associated with immune abnormalities,and the importance of various immune cells and immune mediators in the pathogenesis of osteoarthritis has been continuously elucidated. OBJECTIVE:To review the role of immune cells and related cytokines in osteoarthritis disease,and provide new ideas for future research and prevention of osteoarthritis. METHODS:Taking"osteoarthritis,knee,macrophages,T cells,B cells,natural killer cells,dendritic cells,cytokines,inflammatory factors,immune cells"as search terms,relevant published literature was searched on CNKI,WanFang,VIP,PubMed and Web of Science databases.After reading the title and abstract for preliminary screening,98 articles were selected for review after reading the full text again. RESULTS AND CONCLUSION:In the past,it was believed that the pathogenesis of osteoarthritis was associated with cartilage wear.In recent years,studies have suggested that osteoarthritis is a chronic inflammatory state in which immune cells are widely involved.With the in-depth study of the pathogenesis of osteoarthritis,scholars believe that the pathogenesis of osteoarthritis is driven by early innate immune response,which will gradually catalyze degenerative changes and eventually lead to changes in the joint microenvironment.Various immune cells and cytokines are the key factors affecting the repair of osteoarthritis.Macrophages and natural killer cells participate in synovial inflammatory reaction,and T cell immune reaction participates in the degradation of osteoarthritis cartilage and aggravates the condition of osteoarthritis.Interleukin-1β secreted by immune cells,interleukin-6,tumor necrosis factor α,interleukin-17 and interleukin-37 play an important role in the pathophysiology of osteoarthritis,among which interleukin-1β is the most important inflammatory factor causing articular cartilage damage.Assessing immunological risk factors at the early stage of osteoarthritis can effectively treat the disease at an early stage,which can significantly reduce disability,morbidity and costs associated with osteoarthritis.At present,the immunomodulatory effect of stem cells and their derived secretions and biomaterials on the treatment of osteoarthritis has been confirmed in different experimental models,but there is still a lot of research to be done before they are used in clinical practice.With the discovery of new therapeutic targets,targeted treatment will bring new hope for the repair of clinical osteoarthritis.

Paclitaxel drug-coated balloons combined with bare metal stents vs. bare metal stents for the treatment of superficial femoral atherosclerosis obliterans / 中华普通外科杂志

Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Observational study on perioperative outcomes of pelvic exenteration / 中华胃肠外科杂志

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.

Effects of G-CSF on proliferation and fibrosis of lens epithelial cells / 西安交通大学学报(医学版)

【Objective】 In recent years, granulocyte colony stimulating growth factor (G-CSF) has been proved to be expressed in the posterior capsule of the lens of posterior capsular opacification (PCO), but its specific role remains unclear. The purpose of this study was to explore whether G-CSF plays a role in PCO. 【Methods】 First, human lens epithelial cells (HLEC-B3) were treated with different concentration of recombinant G-CSF protein and screened for effective appropriate concentration. Then, Western blotting was used to detect the effects of extracellular matrix (ECM) synthesis and epithelial mesenchymal transdifferentiation (EMT) marker genes after G-CSF treatment on HLEC-B3 cells. Finally, the effects of G-CSF treatment on the migration and invasion of HLEC-B3 cells were detected by scratch experiment and Transwell test. 【Results】 G-CSF at 80 μg/L could promote the proliferation of HLEC-B3 cells. After G-CSF was treated for 48 h, the expressions of EMT and ECM synthesis marker genes in HLEC-B3 cells were significantly upregulated with time. G-CSF could significantly promote HLEC-B3 cell invasion after 48 h induction. Similarly, G-CSF could also significantly induce cell migration compared to the CTRL group. 【Conclusion】 G-CSF can promote the proliferation, migration and invasion of HLEC-B3 cells, as well as EMT and ECM synthesis, which might be involved in the occurrence of PCO. Inhibiting the expression of G-CSF may be a new strategy for PCO prevention.

Advances and challenges in clinical research on hepatic hydrothorax / 临床肝胆病杂志

Hepatic hydrothorax (HH) is a challenging complication of liver cirrhosis associated with portal hypertension, and its pathogenesis and therapeutic measures remain unknown. This article summarizes and reviews the advances and challenges in the research on the pathogenesis, clinical manifestations, diagnosis, and treatment of HH and proposes a multidisciplinary treatment strategy, including reducing the production of ascites, preventing effusion from entering the thoracic cavity, removing pleural effusion, occluding the pleural cavity, and performing liver transplantation, so as to provide a reference for more clinicians.

Epidemiological analysis of incidence rate, surgical rate and spontaneous cure of indirect inguinal hernia in children of Xinjiang region / 中华消化外科杂志

Objective:To investigate the incidence rate, surgical rate and spontaneous cure of indirect inguinal hernia in children of Xinjiang region.Methods:Children, aged from 4?14 years, coming from 24 kindergartens, 18 primary schools and 9 junior middle schools of 3 countries and 5 cities in Xinjiang Uygur Autonomous Region were recruited to participate as respondents. The survey time for baseline data collection was from May 2013 to June 2014 and the retrospective cross-sectional survey was conducted. Parents of children were investigated by questionnaire, and children were examined on site. Observation indicators: (1) results of questionnaire survey; (2) illness and treatment of children involved in the study; (3) follow-up. Follow-up was conducted using telephone interview. Children who had been diagnosed and not been treated surgically at the time of questionnaire survey were followed up to detect disease progression and treatment in the past 5 years. If the symptoms of a child had disappeared during follow-up, parents of the child should accompany the child to hospital for physical examination and B-ultrasound examination to confirm the diagnosis, and then follow-up was conducted by telephone interview. The follow-up was up to January 2020. Count data were described as absolute numbers and percentages, and compari-son between groups was conducted using the chi-square test. Odds ratio and 95% confidence interval were calculated. Results:(1) Results of questionnaire survey. A total of 19 132 question-naires were distributed, and 19 132 complete questionnaires were recovered. Of the 19 132 children who completed the questionnaire survey, there were 9 670 males and 9 462 females. (2) Illness and treatment of children involved in the study. ① Incidence of indirect inguinal hernia in children with different sexes. Of the 19 132 children, 498 cases were diagnosed as indirect inguinal hernia, including 368 boys and 130 girls, with the prevalence as 3.806%(368/9 670) and 1.374%(130/9 462), respectively. There was a significant difference in the prevalence of indirect inguinal hernia between boys and girls ( χ2=111.54, P<0.05). The proportion of boys and girls in children with indirect inguinal hernia was 73.896%(368/498) and 26.104%(130/498), respectively, with the ratio of 2.8:1. The prevalence of boys was higher than girls ( odds ratio=2.84, 95% confidence interval as 2.32?3.48).② Age of children at first onset. Of the 498 children with indirect inguinal hernia, 59 cases were aged 1?4 years at first onset including 54 boys and 5 girls, 264 cases were aged 5?8 years including 196 boys and 68 girls, 148 cases were aged 9?12 years including 104 boys and 44 girls, 27 cases were aged 13?14 years including 14 boys and 13 girls. There was a significant difference in the age of children at first onset between boys and girls ( χ2=17.33, P<0.05). ③ Pathogenic factors in children with indirect inguinal hernia. Of the 498 children with indirect inguinal hernia, 457 cases had complete family history and crying history, and 41 cases were missing. Family history: of the 457 children with indirect inguinal hernia who had complete family history, there were 175 cases with the family history of indirect inguinal hernia and 282 cases without the family history. Of the 478 healthy children surveyed in the same period, there were 25 cases with the family history and 453 cases without the family history. There was a significant difference in the family history between the 457 children with indirect inguinal hernia and the 478 healthy children ( χ2=515.89, P<0.05). Crying history: of the 457 children with indirect inguinal hernia who had complete crying history, there were 194 cases with obvious crying history and 263 cases without obvious crying history. Of the 496 healthy children surveyed in the same period, there were 99 cases with obvious crying history and 397 cases without obvious crying history. There was a significant difference in the crying history between the 457 children with indirect inguinal hernia and the 496 healthy children ( χ2=56.51, P<0.05). ④ Surgical treatment. Of the 498 children with indirect inguinal hernia, 233 cases underwent surgical treatment including 217 boys and 16 girls, 265 cases were followed up without surgical treatment including 151 boys and 114 girls. The surgical rate for indirect inguinal hernia in boys and girls was 58.967%(217/368) and 12.308%(16/130), respectively, showing a significant difference between them ( χ2=84.01, P<0.05). The operation ratio of boys and girls was 13.6:1, and the surgical rate of boys was higher than girls ( odds ratio=10.24, 95% confidence interval as 5.83?17.98). (3) Follow-up. All the 265 children without surgical treatment for indirect inguinal hernia were followed up for 5 years. During the follow-up, there were 142 of 151 boys with surgical treatment and 9 boys without surgical treatments, showing negative in spontaneous cure. There were 27 of 114 girls with surgical treatment and 87 girls without surgical treatment, showing 55 cases positive in spontaneous cure and 32 cases still with indirect inguinal hernia. There was a significant difference in spontaneous cure between the 151 boys and the 114 girls ( χ2=143.79, P<0.05). Conclusion:In Xinjiang region, the incidence rate and surgical rate of indirect inguinal hernia are lower in girls compared with boys, and the spontaneous cure rate is higher in girls compared with boys.

Drug-coated balloon for in-stent restenosis in femoropopliteal segment: 1-year clinical outcomes from a multicenter study in China / 中华普通外科杂志

Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.

Modified Xiaoyao Erxian Decoction in Treatment of Mood Disorders in Perimenopausal Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Xiaoyao Erxian decoction in the treatment of mood disorders among perimenopausal syndrome due to kidney deficiency and liver depression and its effects on monoamine neurotransmitters and brain-derived neurotrophic factor （BDNF）. Method:According to the random number table， 108 patients were divided into a control group （54 cases） and an observation group （54 cases）. Control group were treated with Shugan Jieyu capsule orally， two capsules per time， two times per day， while those in the observation group received the modified Xiaoyao Erxian decoction， one bag per day， for 12 consecutive weeks. Before and after treatment， the Hamilton Anxiety Scale （HAMA）， 17-item Hamilton Depression Rating Scale （HAMD-17）， modified Kupperman Index （KI）， Pittsburgh Sleep Quality Index （PSQI）， Menopause-specific Quality of Life （MENQOL） and kidney deficiency and liver depression syndrome scores were calculated. The levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， BDNF， 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA） were detected， followed by safety evaluation. Result:The HAMA， HAMD-17， KI， kidney deficiency and liver depression syndrome， PSQI， and MENQOL scores of the observation group were lower than those of the control group （<italic>P</italic><0.01）， whereas the 5-HT， E₂， DA， NE， and BDNF levels in the observation group were higher （<italic>P</italic><0.01）. The clinical efficacy of the observation group was superior to that in the control group （<italic>Z</italic>=2.184， <italic>P</italic><0.05）. No adverse reactions occurred after the oral administration of Chinese medicinal preparations. Conclusion:The modified Xiaoyao Erxian decoction effectively alleviates the mood disorders and other related symptoms of perimenopausal syndrome due to kidney deficiency and liver depression by regulating the monoamine neurotransmitters， BDNF， and E₂， without inducing obvious side effects.

Efficacy of Modified Huanglian Wendantang and Shaofu Zhuyutang Against Ovulation Disorder in Combined Phlegm and Stasis-Induced Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huanglian Wendantang and Shaofu Zhuyutang in the treatment of ovulation disorder in patients with polycystic ovary syndrome （PCOS） due to the combined phlegm and stasis-induced and its influence on chronic inflammation. Method:According to the random number table， 100 patients were divided into a control group （50 cases） and an observation group （50 cases）. Apart from lifestyle intervention and oral administration of clomiphene citrate （CC） capsules to induce ovulation， patients in the control group further received Guizhi Fulingwan， 6 g/time， 2 times/day， while those in the observation group were treated with the modified Huanglian Wendantang and Shaofu Zhuyutang， 1 dose/day， for six menstrual cycles. The ovulation， endometrial thickness， proportion of type A endometrium， as well as the pulsatility index （PI） and resistance index （RI） of uterine artery were monitored before and after treatment. The fasting blood glucose （FBG）， fasting insulin （FINS）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， high-sensitivity C-reactive protein （hs-CRP）， adiponectin （APN）， and interleukin-6 （IL-6） levels before and after treatment were detected， followed by the calculation of homeostasis model assessment-insulin resistance （HOMA-IR） value and the evaluation of ovarian volume and combined phlegm and stasis-induced syndrome score. Result:The overall response rate of the observation group was （44/47） 93.62%， which was higher than （36/46） 78.26% of the control group （<italic>χ</italic>²=4.802， <italic>P</italic><0.05）. The ovulation rate in the observation group was （199/264） 75.38%， higher than （173/272） 63.60% in the control group （<italic>χ</italic>²=8.714， <italic>P</italic><0.01）. The clinical pregnancy rate of the observation group was （11/47） 23.40%， higher than （5/46） 10.87% of the control group， but the difference was not statistically significant （<italic>χ</italic>²=2.564， <italic>P</italic>>0.05）. Compared with the control group， the observation group exhibited reduced PI， RI， LH， T， DHEAS， FINS， FPG， HOMA-IR， TNF-<italic>α</italic>， hs-CRP， and IL-6 （<italic>P</italic><0.01）， but elevated E₂， FSH， and APN （<italic>P</italic><0.01）. Besides， the bilateral ovarian volume and combined phlegm and stasis-induced syndrome score of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， while the endometrial thickness and proportion of type A endometrium were higher （<italic>P</italic><0.01）. Conclusion:On the basis of CC treatment， the modified Huanglian Wendantang and Shaofu Zhuyutang alleviates the ovulation disorder in PCOS patients of combined phlegm and stasis-induced syndrome and regulates IR and chronic inflammation， thus creating a favorable condition for clinical pregnancy， which is worthy of further research.

Generalized Pooling for Robust Object Tracking.

Feature pooling in a majority of sparse coding-based tracking algorithms computes final feature vectors only by low-order statistics or extreme responses of sparse codes. The high-order statistics and the correlations between responses to different dictionary items are neglected. We present a more generalized feature pooling method for visual tracking by utilizing the probabilistic function to model the statistical distribution of sparse codes. Since immediate matching between two distributions usually requires high computational costs, we introduce the Fisher vector to derive a more compact and discriminative representation for sparse codes of the visual target. We encode target patches by local coordinate coding, utilize Gaussian mixture model to compute Fisher vectors, and finally train semi-supervised linear kernel classifiers for visual tracking. In order to handle the drifting problem during the tracking process, these classifiers are updated online with current tracking results. The experimental results on two challenging tracking benchmarks demonstrate that the proposed approach achieves a better performance than the state-of-the-art tracking algorithms.

The role of DUSP6 in TGF-β2-induced epithelial-mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells / 西安交通大学学报(医学版)

【Objective】 To investigate the role of dual-specific phosphatase 6 （DUSP6） in the regulation of human lens epithelial cells （HLECs） epithelial-mesenchymal transition （EMT） and extracellular matrix （ECM） synthesis induced by transforming growth factor β2 （TGF-β2）. 【Methods】 Human lens epithelial B3 （HLE-B3） cells were treated with 10 μg/L of TGF-β2 for 0 h，12 h， 24 h and 48 h. Then we detected the expressions of α-smooth muscle actin （α-SMA） and fibronectin （Fn） by real-time fluorescent quantitative PCR （RT-qPCR） and Western blotting. The overexpression vector of DUSP6 was constructed and transfected into HLE-B3 cell line and divided into three groups： TGF-β2， empty vector （EV）+TGF-β2， and DUSP6+TGF-β2. RT-qPCR and Western blotting were used to detect the effect of overexpression of DUSP6 on the expressions of α-SMA and Fn. Scratch test and Transwell migration test were used to evaluate the effect of DUSP6 overexpression on cell migration. 【Results】 Compared with the control group， the expressions of DUSP6 mRNA and protein decreased after 10 μg/L of TGF-β2 treatment for 24 h （P<0.05）. Compared with EV+TGF-β2 group， DUSP6+TGF-β2 group inhibited the migration of HLE-B3 cells and the expressions of α-SMA and Fn （P<0.05）. 【Conclusion】 DUSP6 could inhibit EMT and ECM synthesis in lens epithelial cells induced by TGF-β2， which might provide a potential therapeutic strategy for posterior capsule opacification.

Research advances in primary biliary cholangitis with hyperlipidemia / 临床肝胆病杂志

Dyslipidemia is one of the most common complications of primary biliary cholangitis (PBC). This article reviews the latest research on lipid profile, the risk of cardiovascular diseases, and treatment of PBC with hyperlipidemia. Different from other liver diseases, PBC with hyperlipidemia has a unique lipid profile, which changes dynamically with disease progression. It is generally not considered that there are increased risks of atherosclerosis and cardiovascular disease. For those who have indications for treatment, statins are recommended as the first choice. In the future, more in-depth systematic studies are needed to clarify its diagnosis, treatment, and management processes.

The whole process management principles of chimeric antigen receptor T-cell therapy for lymphoma at Peking University Cancer Hospital / 白血病·淋巴瘤

Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Application of lymphocytes test in peripheral blood of patients with systemic sclerosis during the treatment / 北京大学学报(医学版)

OBJECTIVE@#To explore the significance of lymphocytes in systemic sclerosis (SSc), by detecting the levels of T lymphocytes, B lymphocytes and natural killer (NK) cells, and analyzing the correlation between the lymphocytes and clinical laboratory indexes.@*METHODS@#The numbers and proportion of T, CD4+T, CD8+T, B, and NK cells were detected by flow cytometry in peripheral blood of 32 SSc patients who had taken immunosuppressive drugs and 30 healthy controls (HC). The comparison of the lymphocyte subsets in SSc with them in the HC groups, and the correlation between the lymphocytes and other clinical and laboratory indicators were analyzed by the relevant statistical analysis.@*RESULTS@#Compared with the HC group, the numbers of T, CD4+T, CD8+T, and NK cells in peripheral blood of SSc group, who had taken immunosuppressive drugs, were significantly decreased (P < 0.05). More-over, the proportion of NK cells in peripheral blood of the SSc group was also significantly lower than that in the HC group (P=0.004). In addition, all the lymphocyte subsets were decreased in peripheral blood of more than 65% of the SSc patients who had taken immunosuppressive drugs. Compared with CD4+T normal group, the positivity of Raynaud's phenomenon, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was significantly increased in CD4+T reduction group, respectively (P＝0.024, P < 0.001, P=0.018). ESR was higher in CD8+T reduction group than CD8+T normal group (P＝0.022). The prevalence of fingertip ulcer was significantly increased in B cell decrease group (P=0.019). Compared with NK cell normal group, the prevalence of fingertip ulcer was significantly increased in NK cell lower group (P=0.033), IgM was remarkablely decreased yet (P=0.049). The correlation analysis showed that ESR was negatively correlated with the counts of T lymphocytes (r＝－0.455, P＝0.009), CD4+T lymphocytes (r＝－0.416, P＝0.018), CD8+T lymphocytes (r＝－0.430, P=0.014), B cells (r＝－0.366, P＝0.039).@*CONCLUSION@#The number of CD4+T, CD8+T, B, and NK cells significantly decreased in peripheral blood of SSc patients who had used immunosuppressive drugs, some lymphocyte subsets might be related with Raynaud's phenomenon and fingertip ulcer, and reflected the disease activity by negatively correlated with ESR and CRP; the numbers of lymphocyte subsets in peripheral blood should be detected regularly in SSc patients who had taken immunosuppressive drugs.

Three-dimensional reconstruction and anatomy of human epididymal duct / 解剖学报

Objective Based on the techniques of continual tissue slices, the human epididymis was rebuilt for understanding the anatomical and histological features of the epididymal ducts. Methods Continuous tissue slices of one human epididymis were performed and digital slice images were obtained through scanning with Leica-Aperio AT2; the pipe wall of epididymal duct was aligned in sequence with Photoshop CC 2018 software and VGStudio MAX V3.0 software was used for three-dimensional synthesis. Finally, the later modification was carried out with Materialise Magics V22.0 software. Another human epididymis was used for electron microscopy. The histological features of epididymal ducts were analysed by combining slices and three-dimensional reconstruction. Results A total of 4331 and 543 slices in transverse and sagittal section respectively were prepared with a thickness of 7 |ira. According to the three-dimensional structure, regional distribution of human epididymal duct could be found obviously and the caput, corpus and cauda of epididymis could be clearly divided into 7, 9 and 4 subregions respectively. There were tissue intervals among adjacent subregions and epididymal ducts were disordered within each subregion, but differences were existed in tubular diameter and epithelial structure, and adjacent subregions were connected by single epididymal duct in the corpus and cauda. Conclusion The human epididymal duct can be successfully reconstructed by continual tissue slices technique. The human epididymal duct has regional distribution in space obviously and there are differences between different subregions.

Establishment and gene expression analysis of drug-resistant cell lines in hepatocellular carcinoma induced by sorafenib / 北京大学学报(医学版)

OBJECTIVE@#To establish the drug-resistant cell lines of hepatocellular carcinoma (HCC) induced by sorafenib, and to screen out the high expression genes in drug-resistant cell lines of HCC induced by sorafenib, then to explore the genes related to sorafenib resistance in hepatocellular carcinoma.@*METHODS@#The human PLC and Huh7 cell lines were obtained, then the PLC and Huh7 drug-resistant cell lines were induced with sorafenib by using intermittent induction in vitro. CCK8 assay was used to detect the IC50 value of sorafenib for evaluation of drug sensitivity of hepatocellular carcinoma cell lines in PLC and Huh7. All the up regulated genes in PLC and Huh7 drug-resistant cell lines induced by sorafenib were screened out using high-throughput cDNA sequencing (RNA-Seq), Ualcan database was used to analyze the correlations between the up regulated genes in PLC and Huh7 drug-resistant cell lines induced and four clinical biological characteristics of hepatocellular carcinoma, including the gene expressions between normal samples and tumor samples, tumor stage, tumor grade, and patient overall survival, to find the genes that might be involved in the mechanism of sorafenib resistance of hepatocellular carcinoma.@*RESULTS@#All the up regulated genes detected by the using high-throughput cDNA sequencing (RNA-Seq) in PLC and Huh7 drug-resistant cell lines were further screened out by following conditions:(1) genes co-expressed in PLC and Huh7 drug-resistant cells induced by sorafenib, (2) the fold change was more than 4 times and the difference was statistically significant (P <0.05), the top 12 up regulated genes in PLC and Huh7 drug-resistant cell lines were found, which were TPSG1, CBX4, CLC, CLEC18C, LGI4, F2RL1, S100A6, HABP2, C15ORF48, ZG16, FOLH1, and EPCAM. Compared with the correlations between the twelve genes and the clinical biological characteristics by Ualcan database, the potentially significant gene CBX4 was screened out.@*CONCLUSION@#The human PLC and Huh7 drug-resistant cell lines of hepatocellular carcinoma induced by sorafenib were successfully established. CBX4, the gene related to sorafenib resistance in hepatocellular carcinoma, was screened out by the high-throughput cDNA sequencing (RNA-Seq) and further analysis using Ualcan database, which is providing a powerful basis for further research on the mechanism of sorafenib resistance of hepatocellular carcinoma.

CD133 overexpression correlates with clinicopathological features of gastric cancer patients and its impact on survival: a systematic review and meta-analysis.

BACKGROUND: CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CD133 in gastric cancer remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to elucidate the correlation of CD133 overexpression with prognosis and clinicopathological features of GC patients. METHODS: A search in the Cochrane Library, PubMed, Medline, Web of Knowledge and Chinese CNKI, CBM (up to Jun 30, 2015) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2.0 software was used for meta-analysis. RESULTS: A total of 603 gastric cancer patients from 8 studies were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons: gastric cancer tissues vs. normal esophageal tissue (OR = 3.49, 95% CI [2.48, 490], P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 2.75, 95% CI [1.99, 3.81], P < 0.00001), distant metastasis vs. non-distant metastasis (OR = 2.38, 95%CI [1.47, 3.85], P < 0.0004), clinical stages III~IV vs. clinical stages I~II (OR = 2.83, 95% CI [2.13, 3.76], P < 0.00001), as well as the accumulative 5-year overall survival rates of CD133-positive vs. CD133-negative patients (OR = 0.23, 95% CI [0.16, 0.33], P < 0.00001). CONCLUSION: Overexpression of CD133 is associated with lymph node metastasis, distant metastasis, poor TNM stage. Additionally, CD133-positive gastric cancer patients had worse prognosis. Our results indicate that CD133 may be involved in the carcinogenesis of gastric cancer. Evaluation of cytoplasmic CD133 overexpression in gastric cancer tissue sections may be useful in the future as a novel prognostic factor. Nevertheless, due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.