2021年 · 第134卷第16期

Hyperplasia of the mammary glands (HMG) is a non-inflammatory and non-tumorous lesion.^[1]It is a structural disorder of the mammary glands due to different degrees of hyperplasia and subinvolution of the mammary parenchyma and stroma. In the literature, HMG is also called mastopathy, fibroadenosis, fibrocystic breast disease, mastalgia, fibrocystic change, benign mammary dysplasia, or sclerosing adenosis.

To standardize the clinical application of implantable intravenous (IV) ports, the Chinese Society of Breast Surgery (CSBrS) of the Chinese Medical Association has identified the key clinical issues through literature research and expert discussion and evaluated the relevant evidence with reference to the grading of recommendations assessment, development, and evaluation. The CSBrS formulated the clinical practice guidelines to provide a reference for physicians specializing in breast cancer and other fields.

The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.

Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.

Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk.

COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is still a threat to global public health, with around 38 million people living with HIV by the end of 2019 (http://www.unaids.org). Until now, there is not a routine cure therapy available for HIV/AIDS.^[1]Anti-HIV inhibitors, such as reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry inhibitors, were all applied in HIV/AIDS patients.^[1]Combined antiretroviral therapy (cART) can effectively control HIV replication, but cannot eradicate the HIV reservoir.^[1]HIV reservoir is the major barrier for HIV cure and is the major cause for HIV rebound after anti-HIV treatment interruption.^[1,2]HIV reservoir, here defined as resting CD4⁺cells that harbor replication-competent HIV, is established in 2 to 3 days of HIV primary infection.^[2]HIV remains quiescent in long-lived memory CD4⁺cells, and therefore is not sensitive to cART.^[1,2]

Colorectal cancer (CRC) is the fourth cause of cancer death in China. We aimed to provide national and subnational estimates and changes of CRC premature mortality burden during 2005-2020.

Data from multi-source on the basis of the national surveillance mortality system were used to estimate mortality and years of life lost (YLL) of CRC in the Chinese population during 2005-2020. Estimates were generated and compared for 31 provincial-level administrative divisions in China.

Estimated CRC deaths increased from 111.41 thousand in 2005 to 178.02 thousand in 2020; age-standardized mortality rate decreased from 10.01 per 100,000 in 2005 to 9.68 per 100,000 in 2020. Substantial reduction in CRC premature mortality burden, as measured by age-standardized YLL rate, was observed with a reduction of 10.20% nationwide. Marked differences were observed in the geographical patterns of provincial units, and they appeared to be obvious in areas with higher economic development. Population aging was the dominant driver which contributed to the increase in CRC deaths, followed by population growth and age-specific mortality change.

Substantial discrepancies were observed in the premature mortality burden of CRC across China. Targeted considerations were needed to promote a healthy lifestyle, expand cost-effective CRC early screening and diagnosis, and improve medical treatment to reduce CRC mortality among high-risk populations and regions with inadequate healthcare resources.

Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC.

We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression.

CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system.

Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.

Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).

A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219-0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m²; OR= 0.489, 95% CI = 0.329-0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700-5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028-2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594-10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661-11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711-6.368), 1.839 (95% CI = 1.028-3.288), and 2.752 (95% CI = 1.197-6.326).

Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.

Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China.

Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates.

The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/10⁵; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/10⁵ and 220.96/10⁵, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/10⁵; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/10⁵ and 93.42/10⁵, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest).

Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.

A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.

V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95% CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.

The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.

http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx? proj=124702).

Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient’s physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.

This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.

A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).

Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

Scoliosis secondary to neurofibromatosis type 1 (NF1) in children aged <10 years is an important etiology of early-onset scoliosis (EOS). This study was performed to investigate the curve evolution of patients with EOS secondary to NF1 undergoing bracing treatment and to analyze high-risk indicators of rapid curve progression.

Children with EOS due to NF1 who underwent bracing treatment from 2010 to 2017 were retrospectively reviewed. The angle velocity (AV) at each visit was calculated, and patients with rapid curve progression (AV of >10°/year) were identified. The age at modulation and the AV before and after modulation were obtained. Patients with (n = 18) and without rapid curve progression (n = 10) were statistically compared.

Twenty-eight patients with a mean age of 6.5 ± 1.9 years at the initial visit were reviewed. The mean Cobb angle of the main curve was 41.7° ± 2.4° at the initial visit and increased to 67.1° ± 8.6° during a mean follow-up of 44.1 ± 8.5 months. The overall AV was 6.6° ± 2.4°/year for all patients. At the last follow-up, all patients presented curve progression of >5°, and 20 (71%) patients had progressed by >20°. Rapid curve progression was observed in 18 (64%) patients and was associated with younger age at the initial visit and a higher incidence of modulation change during follow-up (t = 2.868, P = 0.008 and <0.001, respectively). The mean AV was 4.4° ± 1.2°/year before modulation and 11.8° ± 2.7°/year after modulation (t = 11.477, P < 0.010).

Curve progression of >10°/year is associated with younger age at the initial visit, and modulation change indicated the occurrence of the rapid curve progression phase.

Treatment of unprotected left main coronary artery (ULMCA) disease with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) has developed rapidly during the past decades. The optimal revascularization strategy has been a subject of debate, with several randomized controlled trials and meta-analyses comparing outcomes of CABG and PCI.^[1]However, patients with prior cerebrovascular events (CVEs) were often excluded from coronary revascularization trials. There is a strong association between coronary artery disease (CAD) and prior CVEs.^[2]Approximately one in eight patients with CAD has a history of CVEs, and that particular patient is at higher risk of worse outcomes after coronary revascularization than patients with CAD alone.^[3]The reason for the co-occurrence of CAD and CVEs might be that atherosclerosis is a diffuse process that may affect different vascular beds including coronary artery and cerebral artery. To date, there are no guidelines providing advice on the optimum modality of revascularization for patients with prior CVEs. It gradually became clear that CABG is the standard care for patients with complex lesions, and PCI with drug-eluting stents (DES) is an acceptable option for patients with less complicated diseases. Thus, CABG seems like a better choice for patients with prior CVEs. But it is also pointed out by trials that more strokes occurred after CABG than PCI.^[4]Currently, no study has assessed the impact of prior CVEs and compared outcomes in real-world patients with ULMCA disease and CVEs treated with PCIvs. CABG. We conducted a real-world, single-center, retrospective study of patients with ULMCA disease including prior CVEs to facilitate this comparison.

Multiple myeloma (MM) is a plasmocytic malignancy which accounts for approximately 10% of all hematologic malignancies. In 2016, over 16,500 new cases were diagnosed in China, and approximately 10,300 patients died of the disease.^[1]In novel-agent era, some patients had a poor prognosis with a median overall survival (OS) of <2 years although they received the therapy regimen containing novel agents and autologous peripheral blood stem cell transplantation (APBSCT) as front-line therapy.

To the Editor:Symptomatic urinary stone events have been reported to impact between 1/200 and 1/2000 pregnancies worldwide. Conservative treatment is the first line of treatment for uncomplicated cases.^[1]About one-third of cases ultimately require active management such as ureteral stent insertion (USI), nephrostomy, and definitive stone treatment.^[2,3]

To the Editor:As acute coronary syndromes (ACS) is common causes of morbidity and mortality in China, they serve as an important case example to assess the impact of these health reforms on the quality, safety, and efficiency of healthcare.^[1]

To the Editor: The sinus node artery (SNA) can be occluded during the percutaneous coronary intervention (PCI), which produces bradycardia. Previous studies showed a high incidence of SNA occlusion (SNO). Improvements in stent design and anti-thrombotic strategies have decreased branch occlusion. Here, we investigated the results of this procedure in our center. The incidence of SNO was 7.0%. The percentage of diameter stenosis of the SNA, SNA originating at a diseased right coronary artery (RCA), and larger RCA/SNA diameter ratio were independent predictors of SNO. Bradycardia occurred in SNO, but only one temporary pacemaker was implanted. SNO and the consequent bradycardia were not rare during PCI for severe RCA in current practice, yet they led to a benign clinical course with few temporary pacemakers. Permanent pacemaker implantation seems to be unnecessary.

To the Editor: Revascularization, regardless of whether it is percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), is still the dominant treatment of severe coronary heart disease (CHD). The long-term clinical outcome of revascularization is unpredictable because of the progression of atherosclerosis continuing after surgery.^[1]Many studies and trials have proven that optimal medical therapy (OMT) with or without revascularization is critical for decreasing the incidence of adverse events and improving quality of life.

To the Editor:Since the first IgE monoclonal antibody was approved by the Food and Drug Administration in the USA in 2003, at least 14 kinds of targeted drugs are in the clinical application or pre-clinical trials. The two monoclonal antibodies targeting IgE are omalizumab and ligelizumab. Four drugs targeting interleukin 4 (IL-4) or IL-4R are pascolizumab, pitrakinra, altrakincept, and dupilumab. Three monoclonal antibodies targeting IL-5/IL-5R are mepolizumab, reslizumab, and benralizumab. Two monoclonal antibodies targeting IL-13 are lebrikizumab and tralokinumab. The monoclonal antibody targeting thymic stromal lymphopoietin (TSLP) is tezepelumab. Th2 cytokine inhibitor is mesylate. These targeted drugs have achieved good results, but most of them are still in the pre-clinical stage. This article reviews the history, marketing situation, indications, contraindications, efficacy, and safety of these targeted drugs.

To the Editor: Transmuscular quadratus lumborum block (TQLB) is known to provide visceral analgesia by blocking sympathetic fibers by spreading into the thoracic paravertebral spaces.^[1]It is relatively safer than other conventional methods of analgesia. However, to our knowledge, there have been no reports of hoarseness associated with TQLB. Herein, we report two cases of hoarseness and discomfort to the throat after TQLB.

To the Editor:Pilomatrixoma is a benign tumor that arises from hair follicle matrix cells and has a low recurrence rate.^[1]Dermatofibrosarcoma protuberans (DFSP) is a low-grade, slowly growing fibroblastic sarcoma with a high local recurrence rate and a low propensity for metastasis.^[2]We report a case that was clinically suspected to be DFSP, but the surgical biopsy confirmed a diagnosis of pilomatrixoma.

To the Editor: With great interest, we read the article by Zhouet al^[1]entitled "Application of bilateral supraclavicular artery island flaps in the repair of hypopharyngeal and cervical skin defects: a case report." The authors explored the potential of bilateral supraclavicular artery island (SAI) flaps for reconstructing through-and-through defects between the hypopharyngeal mucosa and the neck skin resulting from salvage surgery for recurrent laryngeal cancer. Although we congratulate the authors on their successful surgical results, we think they should present more details about the surgical method, especially regarding the pre-operative imaging of the SAI flap, which was of crucial importance to the success of the surgery. We would like to take the opportunity to offer some comments and further expand on the topic by presenting our current work involving the SAI flap.