Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Interpretation and consideration of “Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” in General Texts of European Pharmacopoeia Potency is a critical quality attribute for controlling relevant biological properties and batch consistency of vaccines.The methods can be divided into in vivo and in vitro methods according to whether animals are used.The in vivo methods are large consuming of animals and time,as well as have large variant detection results.In contrast,the in vitro alternative methods have been the hotspot of research due to their simple operations,in line with 3Rs principles,and more stable results.However,owing to the complexity of experimental design and the lack of corresponding guidance,the research progress of alternative methods is slow.Recently,“Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” was adopted in the European Pharmacopoeia(10th Edition),which clarifies the critical points of consideration for substitution.This paper interprets the chapter and puts forward some thoughts on that in China,which is expected to speed up the alternative methods research and improve the ability of vaccine quality control and supervision in China.

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3^rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB₁, vitaminB₂, vitaminB₆, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.
Humans ; Male ; Acidosis, Lactic ; Brain ; Brain Stem ; Dystonia ; Dystonic Disorders ; Mitochondrial Diseases ; Infant

Objective:To understand the current status of kidney transplant patient empowerment and explore the factors affecting kidney transplant patient empowerment.Methods:This study was a cross-sectional survey. From September to November 2022, convenience sampling was used to select 201 patients who were followed up by the Renal Transplantation Department of Shanghai General Hospital as the study subject. A survey was conducted using the Patient General Information Questionnaire, Client Empowerment Scale (CES), General Self-Efficacy Scale (GSES), Nurse-Patient Trust Scale, and Chinese Version of Chronic Illness Resource Survey (CV-CIRS). Multiple linear regression analysis was used to explore the influencing factors of empowerment levels in kidney transplant patients.Results:A total of 201 questionnaires were distributed and 197 valid questionnaires were collected, with an effective recovery rate of 98.01% (197/201). The total empowerment score of 197 kidney transplant patients was (161.85±13.08). Multiple linear regression analysis showed that willingness to participate in health decision-making, general self-efficacy, and chronic disease resource support were the influencing factors for kidney transplant patient empowerment ( P<0.05) . Conclusions:The empowerment of kidney transplant patients is at a moderate to upper level. The willingness of patients to participate in health decision-making, general self-efficacy, and chronic disease resource support are influencing factors for kidney transplant patient empowerment.

Photoimmunotherapy (PIT) is an emerging tumor-targeted phototherapy that combines the tumor specificity of monoclonal antibodies with the phototoxicity of light absorbers to rapidly and selectively induce the immunogenic death of target tumor cells. PIT has minimal side effects due to its high specificity. The immunogenic cell death induced by PIT results in rapid maturation of immature dendritic cells proximal to dying tumor cells. Subsequently, the mature dendritic cells present the tumor antigens to CD8+ T cells and induce their activation and proliferation, thus enhancing the antitumor immune response of the host. PIT can also improve the anticancer efficacy by enhancing the penetration of nanomedicines into tumor tissues. In view of the excellent application prospects of PIT, this review summarizes the advances in the immune activation mechanism of PIT, the superenhanced permeability and retention effect, and the new strategies for combinatory therapy, providing references for future research and clinical translation.
Antibodies, Monoclonal/therapeutic use* ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Photosensitizing Agents ; Phototherapy

With the development of precision medicine and individualized treatment, tissue biopsy in cancer patients diagnosis and therapy has been broadly used. However, because it’s hard to collect enough samples for biliary tract tumors, liquid biopsy was broadly applied for the diagnosis. In liquid biopsy, circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes carrying tumor-specific information are released from tumor tissue into blood, bile, and other body fluids, which makes tumor biopsy samples easily to be obtained in a non-invasive way. At the same time, through a series of morphological and molecular measurements as well as genetic characterization, liquid biopsy can be used to look for the new early diagnostic markers, and therapeutic targets, monitoring progression and prognosis of diseases. This article outlined the current technology used to detect circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes, and summarizes the latest advances in the clinical application of liquid biopsy in biliary tract cancers.

Objective:To compare and observe the changes in choroidal thickness between healthy pregnant women and healthy non-pregnant women.Methods:A prospective clinical study. From January 2019 to August 2019, healthy pregnant women (pregnant women group) and healthy non-pregnant women age-matched were enrolled during the same period (the normal group) in the obstetrics of Zhuji People's Hospital. All patients were enrolled with their right eyes. Frequency-domain OCT-enhanced depth imaging technology was used to measure the subfoveal macular and 1000 μm above, below, nasal, and temporal choroidal thickness and foveal retinal thickness (CMT). The choroidal thickness and CMT of the pregnant women group and the normal group were compared by t test, and the choroidal thickness and CMT of the normal group and the eyes of different gestational weeks were compared by one-way analysis of variance. Results:The pregnant women group and the normal group included 161 patients (161 eyes) and 40 patients (40 eyes). According to the different gestational weeks, the pregnant women were divided into the first trimester group, the second trimester group, and the third trimester group, with 47 patients (47 eyes), 66 patients (66 eyes), and 48 patients (48 eyes) respectively. There was no significant difference in age, axial length, intraocular pressure, and CMT between the different gestational week groups and the normal group ( F=1.433, 1.558, 0.416, 2.288; P>0.05). The subfoveal choroidal thickness (SFCT) of the pregnant women group and normal group were 317.7±73.9 μm and 279.7±44.1 μm, respectively, and the difference was statistically significant ( t=3.113, P=0.002). Compared with the normal group, the choroid at the upper, lower, nasal, and temporal sides of the pregnant group 1000 μm from the fovea was thickened. The difference between the upper, nasal and temporal sides was statistically significant ( t=2.699, 3.474, 2.595; P<0.05). The SFCT of the eyes in the first trimester group, the middle group, and the late group were 305.8±72.3, 327.7±69.8, 315.8±80.5 μm, respectively. Compared with the normal group, the difference was statistically significant ( F=4.180, P=0.007). Pairwise comparison between the two groups, the second trimester group was significantly different from the normal group ( P=0.003). There was no significant difference among the first trimester group、the third trimester group and the other groups ( P>0.05). Conclusion:The choroidal thickness of pregnant women is thicker than normal, and the choroidal thickness in the second trimester reaches the maximum value; while the macular CMT during pregnancy has no significant change.

Peptides have been extensively used in the fields of gene/drug delivery and disease targeting therapy. However, natural peptides are sensitive to protease digestion with short circulatory half-lives in vivo. Many studies on structural modifications of peptides have been reported to improve the delivery or therapeutic effect. In this review we focus on the recent literature on peptide stability in accordance with different structural modifications and summarize the methods and influential factors that are involved in the improvement of stability and half-life in vivo. This review will provide the scientific basis and theoretical references for further investigations and applications in vivo.

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome