Objective To observe the changes to,and possible mechanism of,intestinal permeability in pigs without direct injury after an abdominal-and intestinal-penetrating injury from firearms in cold environment at high altitudes.Methods Fifty-five experimental pigs were divided into two groups:high-altitude cold group(HC)and low-altitude normal temperature group(LN).According to the observation time,each group was divided into five experimental subgroups:0h,2h,4 h,8h,and 24 h.There were six pigs in each HC subgroup and five pigs in each LN subgroup.After euthanasia,intestinal tissues were taken,and the levels of the inflammatory factors TNF-α,and IL-6 in intestinal homogenate and the concentrations of intestinal permeability-related proteins DAO and D-lactate acid in blood were detected by ELISA method.The intestinal tissues of experimental pigs were taken at 0 h and 8 h for LN and 8 h for HC,and intestinal pathological changes were observed and scored after HE staining.The concentrations of Occludin,ZO-1,Claudin-3,TLR4,NF-κB,and MLCK(proteins related to intestinal permeability)were detected by Western blot to explore the effect of a cold environment at high altitude on secondary intestinal permeability changes after injury and the possible mechanisms.Results Both the HC group and LN group experienced typical abdominal intestinal penetrating injuries,and there were no significant differences in their abdominal infection scores or intestinal adhesion(P＞0.05).The levels of DAO and D-LA in the serum of experimental pigs in the HC and LN groups gradually increased over time.The levels of DAO and D-LA in the HC group were significantly higher than those in the LN group at all time points(P＜0.01 or P＜0.001).The fastest increase in DAO and D-LA in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The pathological score of intestinal tissue in the HC group was significantly higher than that in the LN group of experimental pigs(P＜0.01).The inflammatory factors TNF-α and IL-6 both increased over time in the intestinal tissue of LN and HC groups.The most significant time point for a increase of inflammatory factors in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The intestinal tissue IL-6 and TNF-α levels of experimental pigs in the HC group were higher than those in the LN group the entire time(P＜0.05,P＜0.01,or P＜0.001).The levels of occludin and ZO-1 in the HC group at 8 h decreased significantly compared to those of the LN group at the 8 h time point(P＜0.05),while claudin-3 showed a significant decrease in LN(P＜0.001).In the HC group,TLR4,NF-κB,and MLCK were both higher than those in the LN group at 8 h,and the difference was statistically significant(P＜0.05).Conclusions A high-altitude cold environment can lead to a secondary increase in intestinal permeability after abdominal-penetrating firearm injury,and its mechanism may be related to the TLR4/NF-κB/MLCK pathway.

Objective:To explore the mechanism by which GSDME promoter methylation regulates the chemotherapy sensitivity of breast cancer (BC) cells through pyrolysis.Methods:Tissues of 54 cases with BC treated with chemotherapy were collected and divided into chemotherapy resistant group and sensitive group. Docetaxel (DTX) was used to treat BC cells to establish drug-resistant BC cells. CCK8 was used to detect cell resistance.qRT-PCR was used to detect the expression of GSDME in tissues and cells. Then sulfite sequencing method was utilized to determine the methylation level of the GSDME promoter methylation site. The expression level of GSDME in DTX-treated BC cells was intervened, and qRT-PCR was used to detect the expression level of Caspase-1, Caspase-4, IL-1β, and IL-18 in cells to assess the degree of cell pyrolysis.Results:Compared with the chemotherapy sensitive group, the expression of GSDME was down-regulated in the chemotherapy resistant group ( t=6.54, P<0.001) . Compared with MCF-10A cells, Caspase-1 ( t=9.14, P<0.001) , Caspase-4 ( t=9.35, P<0.001) , IL-1β ( t=6.13, P=0.004) , and IL-18 ( t=5.49, P=0.005) expression level in MCF-10A/DTX cells were decreased, however, the above indicators were up-regulated after overexpression of GSDME in MCF-10A/DTX cells. Hypermethylation in GSDME promoter region led to a decrease in mRNA expression ( t=12.56, P<0.001) . In tolerance tissues, the methylation level in the GSDME promoter region was negatively correlated with the mRNA level ( r=-0.57, P=0.010) . After treating MCF-10A/DTX cells with 5-azacytidine, a methylation inhibitor,Caspase-1, Caspase-4, IL-1β, IL-18 levels were significantly increased, and GSDME level were up-regulated. Conclusion:Hypermethylation in the promoter region of GSDME leads to decreased mRNA expression, inhibits pyrolysis of BC cells, and reduces the sensitivity of DTX chemotherapy.

Background::This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice.Methods::The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.Results::A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups ( P = 0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the +exemestane group, 9.7 months (95% CI 6.3–13.1) in the +letrozole group, 7.8 months (95% CI 5.5–10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2–11.3) in the +toremifene group, and 6.1 months (95% CI 1.2–11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-na?ve group (50.0% vs. 82.2%, P < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-na?ve group (3.4 months vs. 8.8 months, P = 0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-na?ve patients (6.1 months, 95% CI 4.7–7.5, P = 0.439). Conclusions::Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus.

The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

Objective:To investigate the anxiety and depression of cancer patients undergoing radiotherapy during the epidemic of COVID-19.Methods:By using self-rating anxiety scale and self-rating depression scale, a cross-sectional survey was conducted during the COVID-19 epidemic period.Results:During the COVID-19 epidemic period, the incidence of anxiety and depression in cancer patients undergoing radiotherapy was 15.8% and 27.7% respectively, of which 12.9% suffered from both anxiety and depression. The average scores of anxiety and depression were 49.4(25/76) and 46.4(25/83), respectively, which were higher than those of the domestic norm. Age is a contributing factor for anxiety, and patients living in urban are more likely to experience depression.Conclusions:The prevalence of anxiety and depression of cancer patients undergoing radiotherapy are higher than healthy people during the COVID-19 outbreak. We should pay more attention to the psychological states of the cancer patients.

Objective: To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy. Methods: The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency. Results: Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210. Conclusions The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

Objective To investigate the quality of life, sexual quality of life and its influencing factors in cervical cancer patients undergoing radiotherapy. Methods Pre-menopausal patients of 87 cases were diagnosed with cervical cancer treated with radiotherapy at Peking Union Medical College Hospital from December 2013 to December 2018 were recruited in this study. The functional assessment of cancer therapy-cervix ( FACT-Cx V4. 0) and the female sexual function index ( FSFI) were evaluated. Demographic and treatment data were collected. The influencing factors were analyzed by multiple linear regression analysis. Results The total score of quality of life was 114( 100-126) , 19( 16-21) for physiology, 21( 18-24) for social/family, 19( 17-21 ) for emotion, 19 ( 14-22 ) for function and 39 ( 34-43 ) for additional attention, respectively. The end time of radiotherapy was the influencing factor of the total score ( P= 0.034 ) , physiology ( P=0) and function ( P=0.008) . Family was the influencing factor of social family dimension ( P=0.010) . The total score of FSFI was 8.0( 5.0-20.5) , 1.8( 1.2-3.0) for sexual desire, 1.5( 0-2.7) for sexual arousal, 0.3( 0-3.6) for vaginal lubrication, 0( 0-3.6) for orgasm, 3.2( 2-4) for satisfaction and 0( 0-3.6) for sexual pain, respectively. The total score was less than 27 in 97%( 84/87) of the patients and had sexual dysfunction. Age was the influencing factor of sexual arousal ( P=0.005) and vaginal lubrication ( P=0.039) . Occupation was the influencing factor of sexual pain ( P=0.004) . Conclusions The quality of life of premenopausal patients with cervical cancer is affected by multiple factors. Radiotherapy-related complications should be actively treated to improve the quality of life and sexual life of patients.

OBJECTIVE： To study the improving effects of echinacoside （ECH） on spatial cognitive function in mice under hypobaric hypoxia environment and its mechanism. METHODS： Totally 60 mice were randomly divided into blank group （normal saline）， model group （normal saline）， positive group （Ginkgo leaf extract tablet，100 mg/kg） and ECH low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 10 mice in each group. Except for blank group， other groups were cultured in hypobaric oxygen chamber to simulate hypobaric hypoxia； they were given relevant medicine intragastrically once a day， for consecutive 7 d （Placing into hypobaric oxygen chamber immediately after medication）. Using the times of horizontal and vertical activities of mice in 2 min as index， negative emotions and spatial cognitive function were evaluated. Histopathological changes of hippocampus in mice were observed by microscopy after HE staining. The levels of SOD， CAT， GSH-Px and MDA in hippocampal tissue of mice were detected. RESULTS： Compared with blank group， the times of horizontal activities， MDA level were increased significantly in model group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were decreased significantly （P＜0.05）； the pyramidal cells in the CA1 area of the hippocampal tissue were arranged loosely， and many pyramidal cells were compressed and stained deeply. Compared with model group， the times of horizontal activities and MDA level were decreased significantly in positive group and ECH high-dose group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were increased significantly （P＜0.05）； the pyramidal cells in the CA1 region of the hippocampal tissue were abundant and closely arranged， and a few of them are constricted and deeply stained. CONCLUSIONS： ECH can improve spatial cognitive impairment of mice under hypobaric hypoxia environment， the mechanism of which may be associated with up-regulation of SOD， CAT and GSH-Px， down-regulation of MDA in the hippocampal tissue.

Objective To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti?programmed cell death protein?1 ( PD?1) antibody, SHR?1210 therapy. Methods The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR?1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone ( ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune?related adrenal insufficiency. Results Until December 14th, 2018, no SHR?1210 related primary adrenal insufficiency occurred, and the incidence of immune?related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3?4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR?1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR?1210. Conclusions The incidence of SHR?1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

Objective To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti?programmed cell death protein?1 ( PD?1) antibody, SHR?1210 therapy. Methods The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR?1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone ( ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune?related adrenal insufficiency. Results Until December 14th, 2018, no SHR?1210 related primary adrenal insufficiency occurred, and the incidence of immune?related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3?4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR?1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR?1210. Conclusions The incidence of SHR?1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.