Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVES: To characterize the biological properties of double-negative T (DNT) cells isolated from leukoreduction filter residues. METHODS: Leukoreduction filters containing residues from 400 mL whole blood units (n=6) were collected from a blood center. Filters were back-flushed with normal saline, and the eluate was concentrated to obtain leukoreduction filter residues. Leukocytes in the residues were counted by dual-fluorescence staining. DNT cells were then isolated from the residues using antibody-mediated adsorption and density gradient centrifugation. Both cryopreserved and fresh unstimulated DNT cells derived from the residues were subjected to in vitro culture. Following culture, cells were assessed for expansion fold, viability, immunophenotype, differentiation status, and cytotoxicity against target cells using dual-fluorescence staining and flow cytometry, with comparisons made to DNT cells derived from whole blood. RESULTS: The leukocyte recovery rate achieved through reverse flushing of the leukocyte reduction filter was (41.9±14.7)%. Compared to whole blood, the DNT cell starting material obtained from filter residues showed no significant difference in total T-cell content (P>0.05). However, the viability and purity of the resulting DNT cell starting materials were significantly lower (both P<0.05). After 17 days of culture, DNT cells from filter residues and whole blood showed no significant differences in expansion fold, immunophenotype, differentiation status, or cytotoxicity toward target cells (all P>0.05). However, the viability of DNT cells from residues was significantly lower than that of whole blood-derived DNT cells [(86.0±4.2)% vs. (92.2±1.2)%, P<0.05]. After thawing (post 3 or 15 days of cryopreservation) and 17 days of culture, DNT cell starting materials from residues showed comparable immunophenotype, expansion fold, and differentiation status to their non-cryopreserved counterparts from the same source (all P>0.05). However, the viability of DNT cells cryopreserved for 3 days [92.4% (91.8%, 92.8%)] and the cytotoxicity against target cells of those cryopreserved for 15 days [91.3% (89.4%, 95.1%)] were significantly higher than those of non-cryopreserved DNT cells [87.8% (82.0%, 89.0%) and 70.9% (67.3%, 80.2%), respectively] (P<0.05). CONCLUSIONS DNT cells derived from leukoreduction filter residues exhibited highly comparable characteristics to those from whole blood in terms of expansion, purity, differentiation, and biological potency. Furthermore, their biological activity post-cryopreservation and revival remained largely similar to non-cryopreserved cells. These findings suggest that leukoreduction filter residues represent a promising alternative source of starting material for manufacturing off-the-shelf, allogeneic DNT cell therapeutics.

The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

A middle-aged female with abnormal liver function indicators was admitted to hospital with obstructive jaundice. Urine protein of the patient was positive, and the color turned green during the retest with sulfosalicylic acid, which was relatively rare. According to the laboratory examination and other auxiliary diagnosis of the patient, the cause of the discoloration was found to be obstructive jaundice induced by choledochal adenocarcinoma, which impeded the excretion of copper ions through the bile of the patient. Copper enters the urine through the circulation of the bile, causing an increase in urinary copper. This provides a theoretical basis for the discovery of this phenomenon in clinical tests.

Objective:To investigate the clinicopathological characteristics of early-onset colorectal cancer.Methods:The retrospective and descriptive study was conducted. The clincopatholo-gical data of 59 206 patients with colorectal cancer in the Surveillance, Epidemiology, and End Results Program of the United States of America From January 1,2010 to December 31,2019 were collected. There were 33 213 males, 25 993 males, aged (50±7)years. Observation indicators: (1) demographic and oncological characteristics of colorectal cancer patients; (2) comparison of clinico-pathological characteristics between early-onset and late-onset colorectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison among groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers, and comparison among groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter H test. Patients with early-onset colorectal cancer were segmented by age, and missing data for categorical variables is set as unknown. Results:(1) Demographic and oncological characteristics of colorectal cancer patients. Of 59 206 patients, there were 23 104 cases with early-onset colorectal cancer and 36 102 cases with late-onset colorectal cancer, and cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years, cases aged 55-59 years were 1 041, 1 740, 3 288, 6 050, 10 985, 15 303,20 799, respectively. (2) Comparison of clinicopathological charac-teristics between early-onset and late-onset colorectal cancer. ① There were significant differences in gender, tumor location, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, tumor M staging, preoperative carcinoembryonic antigen (CEA), perineural invasion, cancer nodule, tumor diameter between patients with early-onset and late-onset colorectal cancer ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, transverse colon were 2 329, 2 139, 579, 1 303 in the 6 350 patients with early-onset right colon cancer. The above indicators were 4 563, 3 945, 902, 1 951 in the 11 361 patients with late-onset right colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=114.27, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 553, 1 354, 6 404, 2 431 in the 10 742 patients with early-onset left colon cancer. The above indicators were 865, 1 798, 9 668, 3 610 in the 15 941 patients with late-onset left colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=35.60, P<0.01). ②Of 23 104 patients with early-onset colorectal cancer, cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years were 1 041, 1 740, 3 288, 6 050, 10 985, respectively. There were significant differences in gender, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, pre-operative CEA, perineural invasion, cancer nodule, tumor diameter among patients of different age groups ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, and transverse colon were 91, 117, 45, 69 in the 6 350 early-onset right colorectal cancer patients aged 13-29 years. The above indicators were 165, 136, 47, 115, 304, 313, 93,201, 614, 535, 151, 330, 1 155, 1 038, 243, 588 in early-onset right colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=36.63, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 32, 83, 260, 95 in the 10 742 early-onset left colorectal cancer patients aged 13-29 years. The above indica-tors were 53, 112, 452, 171, 95, 230, 867, 342, 149, 337, 1 702, 665, 224, 592, 3 123, 1 158 in the 10 742 early-onset left colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=47.84, P<0.01). Conclusions:Compared with late-onset colorectal cancer, early-onset colorectal cancer are more likely to occur in the left colon and rectum, with poorly differentiated and undifferentiated tumors, histological type of mucinous adenocarcinoma, TNM staging of stage Ⅲ and Ⅳ, higher proportion of nerve infiltration and cancer nodules, and larger tumor diameter. There are significant differences in clinicopathological characteristics of tumors among patients with early-onset colorectal cancer of different age groups.

Objective:To explore the coverage of influenza and pneumonia vaccination and factors influencing the vaccination in children.Methods:A cross-sectional questionnaire survey was conducted in children's parents in Beijing and Gansu by using two-stage cluster-sampling to investigate the influenza and pneumonia vaccination rates and influencing factors in children.Results:A total of 2 377 parents were included in the study, and the results indicated that the influenza vaccination coverage was 35.93% and the pneumonia vaccination coverage was 16.58% in children in survey areas, the vaccination rate of both vaccines was 11.65%. The top three reasons for vaccination for both vaccines were being aware of severity of the diseases (influenza vaccine: 36.02%; pneumonia vaccine: 49.61%), being required by school or organization (influenza vaccine: 28.76%; pneumonia vaccine: 25.45%) and being aware of the susceptibility of the diseases (influenza vaccine: 26.41%; pneumonia vaccine: 13.88%). The top three reasons for having no vaccinations were personal unwillingness, concern about vaccine and vaccine accessibility. Families with multi children, living in rural areas and lower family income were the negative factors for both types of vaccinations.Conclusions:The influenza and pneumonia vaccination coverage in children need further improvement, and rural families and families with multi children are the key concern groups for expanding vaccination coverage. Health education about influenza and pneumonia vaccinations, coordinating vaccine supply and decreasing vaccine prices play an important role in improving influenza and pneumonia vaccination coverage.

IntroductionTo validate the effect of ethylene oxide sterilization of disposable electronic analgesia infusion pumps and determine the residual amount. MethodsAccording to ISO 11135：2014 Sterilization of Healthcare Products⁃Ethylene Oxide⁃Requirements for the Development， Validation and Routine Control of Sterilization Process for Medical Devices， qualification of physical cycle performance and microbial cycle performance were conducted on disposable electronic analgesia infusion pumps， and sterilization effect was then validated by using sterility test. According to ISO 10993⁃7：2008 Biological Evaluation of Medical Devices—Part 7： ethylene oxide sterilization residuals， the residual amount of ethylene oxide were further measured. ResultsThe sterilization effect fulfilled the requirements under the physical conditions of 38.0‒45.4 ℃ and 46%‒81% humidity. When the temperature was lower than 35 ℃ and the humidity was higher than 71%， the bacterial tablets remained fully activated after the sterilization with ethylene oxide. The shortest survival time without biological indicator after exposure to ethylene oxide was 8h. Furthermore， the residual amount of ethylene oxide after the sterilization was lower than the minimum detection limit. ConclusionAll tested products are sterilized. Sterilization equipment and sterilization process fulfilled the requirements of ISO 11135：2014. Additionally， the sterilization residual amount conforms to the limit values of ISO 10993⁃7：2008.

Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.