Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a "turning point". The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

Talents and science-technology pave the way to precise management of chronic diseases——Reflection and endeavor from The First Affiliated Hospital of Sun Yat-sen University / 中华内分泌代谢杂志

Chronic disease management is a challenging issue in China. To address the needs of talents and mature innovation ecosystem related to chronic disease management, The First Affiliated Hospital of Sun Yat-sen University(FAH-SYSU) actively responds to the national strategy to promote the high-quality development of the hospital through strengthening strategic planning, top-level design, and systematic consideration. Precise management of chronic diseases was taken as key measure for the construction of a national medical center. With continuous exploration in establishing talent pool, innovation center and application platform, and chronic disease management system that focuses on core elements of talent and innovation, the FAH-SYSU Model for the precise management of chronic diseases has been initially formed.

Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 AU/ml to 8.8 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly "non-responders" but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.

Training and reployment of non-specialists is an effective solution for the shortage of health care workers in the COVID-19 pandemic

ImportanceIn the COVID-19 pandemic many countries encounter problems arising from shortage of specialists. Short intensive training and reployment of non-specialists is an option but the effectiveness is unknown. ObjectiveTo investigate whether there was difference in in-hospital mortality rates between COVID-19 patients managed by a mixed team (including non-specialists who had short intensive training and operated to a strict protocol) and those managed by a specialist team of health care workers. DesignCohort study, from January 26, 2020 to April 7, 2020, follow up to April 7, 2020. SettingMulticenter - Wuhan Hankou Hospital and Wuhan Xiehe Hospital, Wuhan, China. Participants261 HCWs deployed to Wuhan from Guangdong emergency rescue team and the 269 COVID-19 patients they treated. ExposureAmong 261 health care workers, 130 were in the specialist team and included 33 physicians, 32 of whom (97.0%) of whom were from relevant specialties. Each physician was in charge of 25-27 beds, with a 6-hour shift time. The mixed team included 131 health care workers, with 7 of the 28 physicians (25.0%) from relevant specialties. Each physician managed 12-13 beds, with a 4-hour shift time. Non-specialists received short-term intensive training and then followed strict management protocols. Specialists practiced as normal. Main Outcomes and MeasuresMain outcome was in-hospital mortality of COVID-19 patients. Another outcome was rate of SARS-CoV-2 infection in health care workers. ResultsA total of 269 patients were included (144 male). In-hospital mortality rate of patients treated by the specialist teams and the mixed teams was 12.6% (20/159) and 12.7% (14/110) respectively (Difference = -0.1%, 95% CI -8.2% to 7.9%, p=.97). None of the health care workers were infected. Conclusions and RelevanceTraining and reployment of non-specialists is an effective solution for the shortage of health care workers in the COVID-19 pandemic. Key PointsO_ST_ABSQuestionC_ST_ABSWas there difference in mortality rates between COVID-19 patients managed by a mixed team (including non-specialists who had short intensive training and operated to a strict protocol) and those managed by a specialist team of health care workers (HCWs)? FindingsIn-hospital mortality rate among patients managed by specialist team (130 HCWs, 159 patients) and mixed team (131 HCWs, 110 patients) was 12.6% (20/159) and 12.7% (14/110) respectively (Difference = -0.1%, 95% CI -8.2% to 7.9%, p=.97). MeaningWith shortage of specialist HCWs, training and reployment of non-specialists is an effective option in the management of COVID-19 patients.

Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study

BackgroundSystemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. MethodsFrom December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. ResultsCorticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p<0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. ConclusionsCorticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.

Exendin-4 does not modify growth or apoptosis of human colon cancer cells.

AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of ß cells as well as colon cancer cells. So, clarifying the effects and mechanisms of GLP-1R agonists on colon cancer cells has important clinical implications. MATERIALS AND METHODS: We investigated GLP-1R expression in human colon cancer tissue samples with immunohistochemisty analysis and explored the effects of exendin-4, a GLP-1 receptor agonist, on colon cancer cells in vitro and in vivo. RESULTS: The results showed lack of GLP-1R expression in both human colon cancer tissues and colon cancer cell lines. Exendin-4 did not enhance the proliferation and migration of colon cancer cell lines in vitro, and nor did it inhibit apoptosis induced by cytotoxic agents such as 5-fluorouracil (5-FU) or irinotecan. In addition, exendin-4 did not promote the propagation of colon cancer cells in vivo. CONCLUSION: Our study suggests that GLP-1R agonists do not modify the growth or survival of human colon cancer cells and may be safe for diabetic patients with colon cancer.

Circulating RNA in thyroid cancer / 中国癌症杂志

Thyroid cancer is the most common endocrine gland malignanct tumor. Numerous studies have found that the content of peripheral blood circulating RNA in various cancer types is aberrantly expressed, which could be a potential biological diagnostic marker and therapeutic target. Tissue-speciifc messenger RNA has a dysregulated expression and may be used for the diagnosis and residual/metastatic detection of thyroid cancer. Recent studies have showed that non-coding RNA (ncRNA) could act as oncogene or tumor suppressor gene in bacteria, fungi and mam-mals. It plays a regulatory role in occurrence and development of tumors and stably exists in peripheral blood. It is hopeful that it will become a new marker for diagnosis of tumors. This review introduces some latest research progress on circulating RNA associated with thyroid cancer; and emphatically discuss the role of mRNA, microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA) in thyroid tumorigenesis and metastasis.

Changes in the endocrine system with aging / 中华内分泌代谢杂志

The endocrine system with the normal aging is characterized by a progressive loss of reserve capacity,resulting in a decreased ability to adapt to environmental demands.This loss of homeostatic regulation reflects important alterations in hormonal synthesis,metabolism,and action.However,these changes may have no significant clinical manifestations,especially under non-stress conditions.This review discusses the endocrine system in the elderly in general.

Practice and reflection on the application of information technology in improving medical education teaching / 中华医学教育探索杂志

This paper elaborates on the importance and necessity of implementing information technology in medical education,the application of information technology in the whole process of medical education,the conceptual construction of medical students' life-long education,the construction of practical teaching resources and the cultivation of information capacity both in teachers and students,etc.In the meantime,this paper introduces the basic framework of medical network and remote education center of Sun Yat-sen University under construction.

Clinical analysis for 51 cases of primary hyperparathyroidism / 中华全科医师杂志

Objective To study clinical characteristics,causes of misdignosis and diagnostic and therapeutic methods for primary hyperparathyroidism (PHPT).Methods Retrospective analysis was done for 51 patients of PHPT,47 confirmed by biopsy after surgical operation and 4 without operation diagnosed based on their serum levels of calcium,alkaline phosphatase ( ALP),intact parathyroid hormone ( iPTH ),and computed tomography (CT) or 99mtechnetium sestamibi (99mTcMIB1) imaging at the First Affiliated Hospital of Sun Yat-sen University,Guangzhou during June 1997 to November 2010.Results Bone-related complications were the most common clinical manifestation,accounting for 51％ (26/51 ) of the cases,and adenoma,a benign,enlarged and hyperactive parathyroid gland,in 34 of 47 cases ( 72％ ).In orthotopic lesions,the right inferior was affected in 19 of 46 cases (41％),followed by the left inferior in 13 cases (28％),while 5 of 51 cases (10％) with ectopic parathyroid gland.PHPT was easily misdiagnosed as urolithiasis,rheumatic disease,primary osteoporosis,etc,accounting for 92％ of the cases in our study.Preoperative serum levels of calcium,ALP and iPTH in the patients varied with their clinical type and pathological classification,the highest in patients with urolithiasis-bone-related complications [ (3.22 ±0.35) mmol/L,(1455 ± 1091 ) U/L and (1669 ± 515 ) ng/L,respectively ] and in patients with parathyroid carcinoma [ (3.46 ± 0.40) mmol/L,( 1410 ± 426) U/L and ( 1861 ± 768) ng/L,respectively ].Sensibility of preoperative localization diagnosis using ultrasonography,CT and 99mTcMIBI was 88％ (35/40),97％ (30/31) and 97％ (31/32),respectively.Conclusions PHPT is frequently misdiagnosed as other diseases.Measurement of serum calcium should be included in routine physical examinations,supplemented with measurement of serum ALP and iPTH,as well as medical imaging,which can help avoid misdiagnosis.CT combined with 99mTcMIBI imaging can improve accuracy of preoperative localization diagnosis.

The changes of insulin secretion in type A insulin resistance syndrome: a 7-year follow up / 中华内科杂志

Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.

The effect of smoking on resting energy expenditure in patients with early diabetic kidney disease / 中华内科杂志

Objective To study the effect of smoking on resting energy expenditure ( REE ) and the relationships among REE, smoking , inflammation and oxidative stress in patients with diabetic kidney disease. Methods A case control study of 31 smokers and 40 non-smokers with early stage of diabetic kidney disease( stage Ⅲ ) were performed to evaluate the chronic effect of smoking on REE. REE/fat free mass( FFM ), biomarkers of oxidative stress malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and inflammation high-sensitivity C-reactive protein (hs-CRP), adiponectin, TNFα were also measured in these subjects. Data were analyzed by Pearson correlation analysis. Results Compared with non-smokers, REE/FFM in smokers group was significantly increased by 15.96% ( P =0.001 ). Pearson analysis showed that smoking was significantly correlated with REE/FFM ( t = 0.395, P = 0.001 ). There were significantly different between smokers and non-smokers in MDA, SOD and hs-CRP ( P＜0.05 ). But no difference between two groups in adiponectin and TNFα ( P ＞ 0.05 ). No significant relationships between REE/FFM and MDA, SOD, hs-CRP, adiponectin, TNFα was found ( P ＞ 0.05 ). Conclusion Chronic smoking can lead to increased REE, arouse oxidative stress and inflammatory in patients with early stage of diabetic kidney disease. However, there is no relationship between increased REE due to smoking and oxidative stress and inflammatory.

Perspective on Metabolic Syndrome in China / 中山大学学报(医学科学版)

Metabolic syndrome is on the rise in China. An improved understanding of the criteria for the diagnosis of this syndrome will lead to important questions for the population in China. The progression of this syndrome to type 2 diabetes mellitus(DM) is a dreaded outcome that may be prevented. Once DM is established,knowledge of the current therapeutic approaches is required.

Investigation on Medical Students' Participation in Series of Lectures by Famous Professors in Multiple Fields / 中华医学教育探索杂志

We analyzed the minus of present medical education,basing on questionnaires of 1773 medical students,including the students' participation rates in lectures of multiple fields and their demands on future lectures.We gave some pieces of advice to solve the problems as well as some references to boost our lectures.

Concomitant Graves' disease and primary hyperparathyroidism: the first case report in mainland of China and literature review / 中华医学杂志(英文版)

Concurrent Graves' disease and primary hyperparathyroidism in the same patient is rare, probably accounts for hypercalcemia in no more than 1 percent of thyrotoxic patients. Hypercalcemia may be noted during the course of hyperthyroidism in as many as 22 percent of cases. The cause of hypercalcemia in a thyrotoxic patient might be due to the activation of osteoclastic bone resorption by the excess thyroid hormone, as the severity of hyperthyroidism correlates positively with osteoclastic activity in trabecular and cortical bone. In 1936, Noble JF et al reported the first case in the world. To our knowledge, only 49 such cases have been described in the literature until the year of 1989. No case has been reported again afterward. The occurrence of hypercalcemia in a patient with hyperthyroidism may present a challenging diagnostic problem. In this communication, we described the first case in mainland of China with hypercalcemia caused by concurrent hyperthyroidism and primary hyperparathyroidism, and the clinical and laboratory characteristics were studied before and after therapy with anti-thyroid medication.

Measuring diameters of thyroid arteries in Graves disease by improving theurapentic effect of intervention radiology / 中华显微外科杂志

Objective In order to select appropriate size of embolizing granules and to achieve complete embolization and good therapeutic effect, the diameters of thyroid arteries in Graves disease was measured. Methods Multiple slides of embolized thyroid tissues from superior pole, body and inferior pole of resected thyroid glands were made. After being embeded and stained, diameters of arteries in various parts of thyroid glands were measured with microscope calipers (Olympus). Results Average diameter capillary network of the thyroid body gland adjacent to superior, infreior artery was 0. 12-0. 25 mm, and the smallest one was 0. 04-0. 11 mm. The diameter of isthmus was 0. 130. 15 mm. The average diameter of superior and inferior artery was 2- 5. 5 mm and 3. 0- 3. 75 mm measured by using interventional angiography Conclusion According to the diameters of arteries which were measured, complete embolization and good therapeutic effect can be achieved.

The relationships of urinary albmnin excretion rate to ambulatory blood pressure and erythrocyte sodium-lithium countertransport in NIDDM / 中华肾脏病杂志

Objective To investigate the potential association among urinary albumin excretion rate(U_(AER)), 24h ambulatory blood pressure(ABP) and erythrocyte sodium-lithium countertransport(SLC) in non-insulin dependent diabetes mellitus (NIDDM). Methods U_(AER), SLC were determined with radioimmunoassay and modified method of Canessa respectively, and 24h ABP profiles were recorded in 69 NIDDM subjects. Results NIDDM patients with increased U_(AER) had higher prevalence of hypertension and higher prevalence of abnormal circadian rhythm of blood pressure. Blood pressure(BP), particularly nighttime systolic BP was also significantly increased. U_(AER) was positively correlated to mean nighttime BP, mean daytime and 24h systolic BP, while inversely related to day-night dip in systolic BP. However, there was no significant difference in SLC between NIDDM subjects with and without increased U_(AER). Futhermore, neither U_(AER) nor all ABP indices were correlated to SLC. Conclusion Close association exists among diabetic nephropathy and increased BP and abnormal diumal BP rhythm, while either SLC and U_(AER) or SLC and BP is significantly correleted. Increased rate of SLC is not likely a marker for diabetic nephropathy in NIDDM, and it seems not to be involved in the pathogenesis of diabetic hypertension.

Pathological evaluation of thyroid glands in Graves' disease after thyroid arteries embolization / 介入放射学杂志

Objective To study the pathological morphology of thyroid specimen after thyroid arteries embolization. In order to select appropriate size of embolizing granules, the diameters of thyroid arteries in Graves' disease were measured. Methods Multiple slides of embolized thyroid tissues from superior pole, body and inferior pole of the resected thyroid glands were made. After being embedded and stained, pathological morphology was observed and diameters of arteries in various parts of thyroid glands were measured under microscopy. Results Pathological examination of thyroid glands showed that superior and inferior thyroid arteries and most of their branches were embolized with ischemic necrosis and fibrosis in the embolized thyroid tissue. Follicular epithelium appeared as flat or cubic shapes with colloid reduction. Average diameter of main branches of superior artery was 440～550?m and that of inferior artery was 300～375?m. The diameters of capillary network in the thyroid body was 120～250?m, and the non embolized ones was 40～110?m. The diameter of isthmus was 130～150?m. Conclusions Pathological morphology of Graves' disease after thyroid arteries embolization showed that the excretion of thyroid glands would be decreased and equivalents to subtotal thyroidectomy.