OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.

Objective:To evaluate the safety and clinical efficacy of hypofractionated radiotherapy (HFRT) at 36.5 Gy in 10 fractions for the chest wall and reginal lymph nodes following modified radical mastectomy for breast cancer.Methods:This was a prospective, single-arm, phase Ⅱ clinical study. A total of 85 patients who received HFRT at 36.5 Gy in 10 fractions to the chest wall ± supraclavicular region following modified radical mastectomy for locally advanced breast cancer from March 2014 to December 2015 were included. The primary endpoint was radiotherapy toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS), and overall survival (OS).Results:The median follow-up period was 98 (94.0-109.0) months. Radiotherapy toxicities were mild. The incidence rates of grade 1 acute cutaneous and pulmonary toxicities were 52.9% and 40%, and those of grade 1 late cutaneous, pulmonary, and cardiac toxicities and upper extremity edema were 10.6%, 29.4%, 2.4%, and 21.2%, respectively. Only 1 (1.2%) patient suffered from grade 2 radiation-induced brachial plexus injury. Of the 85 patients, one patient had regional recurrence (supraclavicular lymph nodes), six patients had distant metastasis, and six patients died of breast cancer. The 9-year LRFFS, DFS, and OS were 97.7%, 91.8%, and 92.8%, respectively.Conclusions:HFRT at 36.5 Gy in 10 fractions following modified radical mastectomy for breast cancer is associated with mild toxicities. A phase Ⅲ study is necessary for validating HFRT's clinical efficacy.

Objective:To compare the short-term clinical effect of gastrointestinal or enterointestinal dominant channels after radical proximal gastrectomy combined with dual-channel anastomosis for upper gastric cancer.Methods:A total of 72 patients in Hefei Second People's Hospital from Jan 2017 to Jul 2021 were retrospectively analyzed, including 29 patients in the total gastrectomy group, and 43 patients in the group of radical proximal gastrectomy+dual-channel anastomosis, and by imaging results it was futher stratified into gastrointestinal dominant channel sub-group (26 cases) and intestinal dominant channel sub-group (17 cases).Results:The number of lymph node dissection in the total gastrectomy group was more than that in the proximal stomach group (27.9±3.2 vs. 25.4±2.9, t=3.441, P<0.05). While the 12 months post operation albumin [(36.1±2.4) g/L vs. (34.1 ± 2.3) g/L, t=3.526, P=0.001], hemoglobin [(122.9 ± 6.9) g/L vs. (115.9 ± 6.0) g/L, t=4.444, P=0.000], vitamin B12 [(349.0±21.7) pmol/ml vs. (77.9±8.5) pmol/ml, t=63.931, P=0.000] level, and the body mass index [(23.01±0.78) kg/m 2vs. (21.95±0.67) kg/m 2, t=5.978, P=0.000] decline level was unfavored ( P<0.05). The 12 months post operation vitamin B12 level, body mass index, albumin and hemoglobin level had no statistical difference in the two subgroups of proximal gastrectomy (all P>0.05). Conclusions:Laparoscopic proximal gastrectomy with double tract reconstruction for proximal gastric cancer is safe and reliable, which can effectively improve the postoperative nutritional status, prevent postoperative anemia.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.
Spliceosomes/metabolism* ; Introns/genetics* ; RNA Splicing ; RNA, Messenger/genetics* ; Cell Nucleus/metabolism*

Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.

Background: Blackened intestines in slaughtered pigs have been commonly observed in China in recent years. However, no cause has been reported. Objectives: We attempted to determine whether the blackening of the pig intestine was related to an excess of copper (Cu) in their feed. Methods: In this study, we observed and collected porcine intestines in small- and large-scale pig slaughterhouses in Shandong province from May to October 2018. Twelve types of metal ions were detected in the black intestinal samples. Results: The Cu level in the intestine samples was mostly higher than the Chinese national limit for food. Further study showed that Cu supplementation in most commercial porcine feed also exceeded the national standard. An animal model (mouse) that could mimic the intestinal blackening in pigs was established. Compared to control mice, Cu accumulated in the liver and intestines of mice fed an excessive Cu level, confirming the excessive Cu in the feed may be considered the major cause of blackened porcine intestines. Microscopic examination revealed that black intestines had many particles containing Cu in the lamina propria of the intestinal mucosa, and the intestinal mucosal epithelial cells showed degeneration and necrosis. Conclusions In conclusion, overuse of Cu in animal feed can lead to animal poisoning and Cu accumulation in animal products. Such overuse not only harms the health of livestock but can also affect public health.

In recent years, immunotherapy has become the hottest topic in the field of oncology. Both the Keynote189 study and the Keynote407 study have confirmed that progression-free survival is significantly prolonged in patients who have been benefited from immune checkpoint blockades in lung cancer. In an article published in The New England Journal of Medicine in 2012, a case report of radiation abscopal effects caused by immunization combined with conventional radiotherapy has attracted great attention in the field of oncology. The Pacific study, published in 2017, expanded the indications for immunotherapy from advanced to locally-advanced non-small cell lung cancer. The second analysis of Keynote001, published in the Lancet Oncology in the same year, suggested that radiation therapy may mediate the immune memory effects, whereas the mechanism and time window are still unclear. With the publication of PEMBRO-RT study and several pieces of work by our team in recent years, various details of radiotherapy combined with immunotherapy (iRT) have become more mature. In clinical practice, iRT is involved in the full treatment of lung cancer. However, iRT is not a hodgepodge or stew that needs further refinement and sorting. In this article, the principles, efficacy in clinical practice, and exploration of the details of iRT were discussed.

Background: Blackened intestines in slaughtered pigs have been commonly observed in China in recent years. However, no cause has been reported. Objectives: We attempted to determine whether the blackening of the pig intestine was related to an excess of copper (Cu) in their feed. Methods: In this study, we observed and collected porcine intestines in small- and large-scale pig slaughterhouses in Shandong province from May to October 2018. Twelve types of metal ions were detected in the black intestinal samples. Results: The Cu level in the intestine samples was mostly higher than the Chinese national limit for food. Further study showed that Cu supplementation in most commercial porcine feed also exceeded the national standard. An animal model (mouse) that could mimic the intestinal blackening in pigs was established. Compared to control mice, Cu accumulated in the liver and intestines of mice fed an excessive Cu level, confirming the excessive Cu in the feed may be considered the major cause of blackened porcine intestines. Microscopic examination revealed that black intestines had many particles containing Cu in the lamina propria of the intestinal mucosa, and the intestinal mucosal epithelial cells showed degeneration and necrosis. Conclusions In conclusion, overuse of Cu in animal feed can lead to animal poisoning and Cu accumulation in animal products. Such overuse not only harms the health of livestock but can also affect public health.

Objective:To investigate and analyze the epidemiological and clinical characteristics of 46 patients with corona virus disease 2019 (COVID-19) in Beijing City.Methods:A retrospective study was conducted to analyze the data of 46 patients with COVID-19 in Beijing from 20th January 2020 to 8th February 2020 at the Fifth Medical Center of the PLA General Hospital in Beijing City. Twelve, 23 and 11 patients were assigned to the mild group, common group and severe group, respectively. The epidemiological history, clinical characteristics, laboratory tests and imaging inspections were analyzed. Statistical analysis used Fisher exact test. If P<0.05, post- hoc test was used for pairwise comparison, and the statistics were corrected by Bonferroni test. Results:Among the 46 patients included in this study, 27 were male and 19 were female. The age range was between 3-79 years old, and the age was (41.8±16.3) years old. The average incubation period was (4.85±3.00) days. A total of 26 cases (56.5%) were clustered patients, and 26 cases had a history of staying in Wuhan, 10 cases had contact with Wuhan personnel. Fever (39 cases, 84.8%), cough (27 cases, 58.7%), and fatigue (25 cases, 54.3%) were the main clinical symptoms for these patients. The decrease in white blood cell counts occurred in 12 patients, four had the decrease in T lymphocyte percentage, 17 had the decrease in CD4 + T lymphocyte counts, seven had the decrease in CD8 + T lymphocyte counts, 21 had the increase level of C reactive protein (45.7%), and interleukin-6 (IL-6) level increased in 32 cases (69.6%), erythrocyte sedimentation rate (ESR) increased in 23 cases (50.0%), serum ferritin level increased in 26 cases (56.5%), and blood lactic acid level increased in nine cases. There were statistically significant differences in the proportion of cases with decreased absolute value of CD8 + T lymphocytes and T lymphocytes counts among the mild, common and severe groups (all P<0.05). Comparing the proportion of cases in the three groups with elevated C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels, the differences were statistically significant (all P<0.05). The proportion of cases with elevated C reactive protein levels in severe group was higher than those in mild and common groups. The proportion of cases with elevated IL-6, ESR, and serum ferritin levels in severe and common group were higher than those in mild group. The proportion of cases with elevated blood lactic acid levels in severe group was higher than those in mild group. The differences between the above groups were statistically significant (all adjusted P<0.017). Analysis of chest X-rays results showed that 34 patients (73.9%) had inflammation in the lungs. Conclusions:The epidemiological characteristics of patients with COVID-19 in Beijing City are mainly imported cases and clustered cases. The clinical manifestations are mainly fever, fatigue and cough. C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels are higher in severe patients.