The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

[摘 要] 目的：探讨miR-216b-5p对食管癌Eca109细胞顺铂（DDP）耐药性的影响及其作用机制。方法:采用qPCR法检测miR-216b-5p在食管癌细胞TE-1、KYSE-150、Eca109和耐药细胞Eca109/DDP中的表达水平。利用脂质体转染技术分别将miR-216b-5p mimic及mimic NC、自噬相关蛋白5（ATG5）过表达质粒转染到Eca109/DDP细胞中，用CCK-8、EdU法和FCM分别检测转染后细胞的增殖和凋亡；mRFP-eGFP-LC3双荧光标记实验检测mRFP-eGFP-LC3慢病毒感染后各组细胞自噬发生情况，WB法检测自噬相关蛋白LC3、Beclin 1和P62表达。用荧光素酶报告基因实验验证miR-216b-5p与ATG5的靶向关系，WB法检测ATG5的表达。建立裸鼠Eca109/DDP细胞移植瘤模型，观察miR-216b-5p过表达对移植瘤生长的影响。结果：miR-216b-5p在TE-1、KYSE-150、Eca109和Eca109/DDP细胞中均呈低表达（均P<0.05）。过表达miR-216b-5p可显著抑制Eca109/DDP细胞的增殖并诱导凋亡（均P<0.05），减少细胞中自噬小体数量（P<0.05），下调LC3Ⅱ/LC3Ⅰ比值和Beclin 1蛋白水平、上调P62蛋白水平（均P<0.05）。双荧光素酶报告基因实验证实miR-216b-5p靶向并负调控ATG5的表达（P<0.05），过表达ATG5可使miR-216b-5p mimic对Eca109/DDP细胞增殖、自噬的抑制作用和凋亡的诱导作用明显减弱（均P<0.05），自噬相关蛋白P62表达降低、LC3Ⅱ/LC3Ⅰ比值和Beclin 1表达升高（均P<0.05）。荷瘤实验结果表明，miR-216b-5p过表达可显著抑制裸鼠移植瘤的生长（P<0.05）。结论：miR-216b-5p过表达可逆转食管癌Eca109/DDP细胞对DDP的耐药性，其机制可能与靶向负调控ATG5表达并影响细胞自噬有关。

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimina-tion of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.

Purpose: Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. Materials and Methods: Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. Results: A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. Conclusion Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Objective:To investigate the influencing factors of post-dialysis hypertension in maintenance hemodialysis (MHD) patients.Methods:This study was a cross-sectional and retrospective study. The patients receiving hemodialysis from January 9, 2017 to January 14, 2017 in 5 hemodialysis centers of Beijing area were selected. Post-dialysis hypertension was defined as an event characterized by an average increase of more than 15 mmHg in post-dialysis mean artery pressure (MAP) compared to intradialytic 3 h MAP during 3 consecutive hemodialysis sessions. Post-dialysis stable blood pressure was defined as an event characterized by an increase of less than 15 mmHg or a decrease of less than 10 mmHg in post-dialysis MAP compared to intradialytic 3 h MAP, with the exception of patients with post-dialysis hypertension and post-dialysis hypotension. The patients were divided into hypertension group and stable blood pressure group based on whether they had post-dialysis hypertension, and the differences of clinical data between the two groups were compared. The influencing factors of post-dialysis hypertension were analyzed by multivariate unconditional logistic regression.Results:A total of 491 MHD patients were enrolled in this study, including 65 patients (13.2%) in the hypertension group, 406 patients (82.7%) in the stable blood pressure group and 20 patients (4.1%) in the hypotension group. The age, blood calcium before dialysis and the proportion of patients using 1.75 mmol/L Ca 2+ dialysate in the hypertension group were higher than those of the stable blood pressure group, and pre-dialysis serum intact parathyroid hormone and pre-dialysis serum uric acid in the post hypertension group were lower than those of the stable blood pressure group (all P<0.05). The age, pre-dialysis serum intact parathyroid hormone, pre-dialysis serum calcium, pre-dialysis serum uric acid, dialysate Ca 2+ concentration of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and post-dialysis serum calcium, pre-dialysis total serum cholesterol, application of β receptor blocker, gender of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. Multivariate logistic regression analysis showed that using 1.75 mmol/L Ca 2+ dialysate was the independent influencing factor of post-dialysis hypertension (with using 1.50 mmol/L Ca 2+ dialysate as reference, OR=2.930, 95% CI 1.282-6.694, P=0.011). The age and pre-dialysis serum calcium of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and pre-dialysis serum sodium and pre-dialysis serum uric acid of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. The older age ( OR=1.046, 95% CI 1.000-1.093, P=0.049) and higher pre-dialysis serum calcium ( OR=21.847, 95% CI 2.111-226.075, P=0.010) were the independent influencing factors of post-dialysis hypertension when the 1.50 mmol/L Ca 2+ dialysate was used. Conclusions:The independent influencing factor of post-dialysis hypertension is using 1.75 mmol/L Ca 2+ dialysate, while the independent influencing factors of post-dialysis hypertension are the older age and the higher pre-dialysis serum calcium level when the dialysate Ca 2+ concentration was 1.50 mmol/L.

Objective:To investigate the clinical effect of the anterolateral thigh perforator chimeric flap in the treatment of the wound of diabetic foot ulcer (DFU) .Methods:From January, 2018 to December, 2019, 14 cases wound of DFU of type II diabetic were treated by anterolateral thigh chimeric perforator flap. The patients were 10 males and 4 females, at 49 to 58 years old. Of the 14 patients, 10 with simple peripheral neuropathy, 4 with peripheral neuropathy complicated with vascular disease, and none with single vascular disease. With strict control of patients' blood glucose, antibiotics blended bone cement was applied or filled onto grade 2 or higher grade Wagner's DFU after debridement. In addition, the anterolateral thigh chimeric perforator flap was transferred 2 to 3 weeks later. The size of flap was 8 cm×3 cm-27 cm×7 cm. Regular followed-up were made after surgery.Results:Thirteen flaps survived in one stage after surgery. The other 1 flap had venous vascular crisis, and survived completely after active exploration. The patients were followed-up for 6-12 months. All the flaps survived well in good shape and texture. The donor and recipient areas healed well. The functional recoveries of the DF were satisfactory.Conclusion:Application of anterolateral thigh perforator chimeric flap in repair of the refractory wound of DF achieves a good clinical outcome and effectively improves the life quality of patients.

Chronic subdural hematoma (cSDH) occurs in acute subdural hemorrhage after head trauma or converts from effusion. Traditional treatment is based on conservative treatment and surgical drainage. The effective rate of conservative treatment is only 3%-18%; even with drilling drainage treatment, the recurrence rate is as high as 33%. Recently, the middle meningeal artery embolization technique based on pathological analysis can greatly reduce the recurrence rate, and the operation is simple and curative effect is exact. This article reviews the pathogenesis of cSDH and progress of interventional therapy.