2021年 · 第134卷第03期

Tissue engineering (TE), which represents the technique of reconstituting or repairing organs and tissues byin vitroculture or construction using biologically active substances, has become one of the most commonly used approaches for tissue reconstruction and regeneration. It is an excellent, available biomaterial that is not only biocompatible and degradable, but can also efficiently transport cells and growth factors to the damaged tissue and provide support to the newly formed tissue until it matures.

Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease that occurs in middle age, and it causes significant social and economic problems. The treatment effects of current modern western medicine on MS have increased. However, there are some serious side effects, such as progressive multifocal leukoencephalopathy and serious infections, which can result from universal immunosuppression.^[1,2,3]

Conventional pressure support ventilation (PS_P) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PS_N) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PS_N and PS_P in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.

Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.

Total AI of PS_N was consistently lower than that of PS_P in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PS_P but not during PS_N in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PS_N than during PS_P in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PS_N and PS_P.

PS_N improves patient-ventilator synchrony and generates a respiratory pattern similar to PS_P independently of any level of support in patients with different respiratory system mechanical properties. PS_N, which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PS_P.

ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.

Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.

In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs.

There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.

Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

The development of the technique has improved the success rate of percutaneous coronary intervention (PCI) for instent chronic total occlusion (IS-CTO). However, long-term outcomes remain unclear. The present study sought to investigate long-term outcomes of PCI for IS-CTO.

A total of 474 IS-CTO patients were enrolled at two cardiac centers from 2015 to 2018 retrospectively. These patients were allocated into either successful or failed IS-CTO PCI groups. The primary endpoint (major adverse cardiac events [MACE]) consisted of recurrent angina pectoris (RAP), target-vessel myocardial infarction (MI), heart failure, cardiac death, or ischemia-driven target-vessel revascularization (TVR) at follow-up. Multivariable Cox regression analysis was used to investigate the association between treatment appropriateness and clinical outcomes.

A total of 367 patients were successfully treated with IS-CTO PCI while 107 patients had failed recanalization. After a median follow-up of 30 months (interquartile range: 17-42 months), no significant difference was observed between the two groups for the following parameters: cardiac death (successful PCI vs. failed PCI: 0.9% vs. 2.7%; adjusted hazard ratio [HR]: 1.442; 95% confidence interval [CI]: 0.21-9.887; P = 0.709), RAP (successful PCI vs. failed PCI: 40.8% vs. 40.0%; adjusted HR: 1.025; 95% CI: 0.683-1.538; P = 0.905), heart failure (successful PCI vs. failed PCI: 6.1% vs. 2.7%; adjusted HR: 0.281; 95% CI: 0.065-1.206; P = 0.088), target-vessel related MI (successful PCI vs. failed PCI: 1.5% vs. 2.7%; adjusted HR: 1.150; 95% CI: 0.221-5.995; P = 0.868), MACE (successful PCI vs. failed PCI: 44.2% vs. 45.3%; adjusted HR: 1.052; 95% CI: 0.717-1.543; P = 0.797). More patients were free of angina in the successful IS-CTO PCI group compared with failed PCI in the first (80.4% vs. 60%, P < 0.01) and second years (73.3% vs. 60.0%, P = 0.02) following up. Successful IS-CTO PCI had a lower incidence of MACE in the first and second years (20.2% vs. 40.0%, P < 0.01; 27.9% vs. 41.3%, P = 0.023) compared with failed PCI. After a median follow-up of 30 months, the reocclusion rate was 28.5% and TVR was 26.1% in the successful IS-CTO PCI group. Receiving >18 months of dual antiplatelet therapy (DAPT) was an independent predictor of decreased risk of TVR (HR: 2.682; 95% CI: 1.295-5.578; P = 0.008) or MACE (without TVR) (HR: 1.898; 95% CI: 1.036-3.479; P = 0.038) in successful IS-CTO PCI.

After a median follow-up of 30 months, the successful IS-CTO PCI group had MACE similar to that of the failed PCI group. However, the successful IS-CTO PCI group had improved angina symptoms and were free from requiring coronary artery bypass grafting in the first or second years. To decrease MACE, DAPT was found to be essential and recommended for at least 18 months for IS-CTO PCI.

Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.

Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.

Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.

Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.

We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.

Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ² = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ² = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ² = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).

Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.

Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.

ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3′,5′-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).

ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB.

Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.

The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4⁺ and CD8⁺ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.

Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups.

Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests.

Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed.

ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.

Psittacosis is a zoonosis caused byChlamydia psittaci, a Gram-negative intracellular bacterium. This condition is caused by the ingestion of contaminated fecal matter and nasal secretions from infected birds. The severity of human psittacosis varies from mild flu-like symptoms to lifethreatening severe pneumonia.^[1]Given thatC. psittaciis not a part of the traditional microbiological diagnosis' human psittacosis is often underreported, misdiagnosed, and inadequately diagnosed. In this study, the clinical data ofC. psittacipneumonia patients were retrospectively analyzed.

Chronic fluid overload (FO) is a well-known factor which contributes to the high morbidity and mortality of patients undergoing hemodialysis (HD).^[1]Higher blood pressure (BP) is commonly associated with overload volume.^[1,2,3,4]Thus, the measurement time point (eg,pre-dialysis and post-dialysis) and volume status may affect the prognostic value of BP in HD patients. This study aimed to examine the correlation between fluid volume and BP, as well as their prognostic effects in HD patients who were free of coronary artery disease (CAD).

Pulmonary embolism (PE) patients have a high recurrence rate of venous thromboembolism (VTE) and recurrences are more often fatal. Recurrence can be effectively prevented by prolonged anticoagulation treatment, but the risk of bleeding also increases. Consequently, risk assessment of VTE recurrence is important in PE patients, as high-risk patients will benefit from long-term anticoagulation treatment, whereas low-risk patients will unnecessarily be exposed to an increased bleeding risk. Several risk factors for VTE recurrence have been identified in non-Asian populations, including male gender, advanced age, thrombophilia, obesity, persistent elevation of D-dimer one month after discontinuation of anticoagulation and residual thrombosis. However, risk factors for VTE recurrence have not been clearly evaluated in Chinese and Asian populations. A recent study found that the European Society of Cardiology (ESC) risk stratification for PE patients (2008 version), which is used to assess the disease severity of acute PE patients, was associated with VTE recurrence.^[1]The simplified pulmonary embolism severity index (sPESI) is also widely validated for the assessment of disease severity of PE, has good prognostic value for early and even long-term mortality. It is less clear whether the model predicts VTE recurrence. The aim of this prospective study was to investigate the short-term and long-term incidence of recurrent VTE after a first episode of acute PE and associated risk factors of recurrent VTE. The association between VTE recurrence and disease severity assessed by sPESI was also evaluated.

To the Editor:Lower respiratory tract infections (LRTIs) are among the deadliest diseases and remain one of the leading causes of death over the last 15 years, especially in low-income countries, and are of great concern to immunosuppressed individuals. Infections located in the peripheral lung field (PLF) are located within the outer-third elliptical regions around the hilum on computed-tomography (CT) scans.^[1]They are surrounded by normal lung parenchyma and are unlikely to be visualized and accurately diagnosed by bronchoscopy. Recent studies have demonstrated the value of virtual bronchoscopic navigation (VBN)-assisted bronchoscopy as a diagnostic tool for small peripheral pulmonary lesions. Metagenomics next-generation sequencing (mNGS) is a new sequencing method comparable to first-generation DNA-sequencing technology. Using mNGS, we can perform high-throughput sequencing on clinical samples to analyze microbial communities. mNGS only requires a small amount of DNA directly taken from the sample, in order to screen for pathogens, as well as a bioinformatics tool, which identifies pathogens by linking sequencing reads to an accurate reference genome (or marker) database. The purpose of the present study was to explore the value of VBN combined with mNGS as a potential diagnostic tool in adults hospitalized with LRTIs.

To the Editor:Chinese Thoracic Society (CTS) updated the Chinese clinical practice guideline for community-acquired pneumonia (CAP) in adults in 2016,^[1]and launched a series of guideline training programs around the nation in 2016 to 2017. To measure the achievements of guideline training programs and identify the problems of CAP management, we performed a national electronic questionnaire survey towards physicians in charge of the management of CAP between March and July 2018.

To the Editor:Hypertrophic cardiomyopathy (HCM) has an increased risk of developing ischemic stroke (5%-10% in unselected HCM patients), whereas hemorrhagic stroke only accounts for no more than 0.6% of HCM patients.^[1]We present a rare case of HCM complicated with hemorrhagic stroke that caused by underlying moyamoya disease.

To the Editor:Alveolar rhabdomyosarcoma (ARMS) of nasal wing with distant metastasis has a very poor prognosis. Because it is difficult to achieve complete surgical excision of the primary site of the nasal wing, distant metastasis is not easy to control. Here, we present an unusual case of a 29-month-old boy with ARMS in the left nasal wing accompanied by bone metastasis who was treated with systemic chemotherapy as well as¹²⁵I interstitial brachytherapy, and this special multidisciplinary management resulted in a perfect prognosis and mild long-term side effects.

To the Editor: A 59-year-old Chinese man who presented with a severe cough and short of breath was admitted into hospital in October, 2018. Computed tomography scan showed a 4.0 cm × 2.0 cm tumor located on the lower lobe of right lung [Figure 1A] and multi-bone lesions, core needle biopsy was performed and adenocarcinoma was confirmed by pathologists. Diagnosis of metastatic lung adenocarcinoma with T4N3M1c in stage IVB was made by oncologists and pathologists. Next generation sequencing (NGS) with the biopsied tumor was done, and epidermal growth factor receptor (EGFR)exon 21 L858R mutation with mutant allele fractions (MAF) of 24.8% was found. Icotinib (Betta Pharmaceuticals Co., Ltd, Hangzhou, China), a first-generation EGFR tyrosine kinase inhibitor (TKI), at a dose of 125 mg orally, three times a day was administered. The patient got a partial response (PR) after 5 months according to the Response Evaluation Criteria in Solid Tumors 1.1 [Figure 1B]. He was found multi-brain metastasis on magnetic resonance imaging and the right lung tumor was enlarged [Figure 1C] after 9 months of icotinib treatment. NGS was done with the new biopsied progressed lung tissue, which indicated that T790M mutation was negative and the MAF ofEGFRexon 21 L858R decreased from 24.8% to 1.83%. Taking into account of the patient’s refusal of recommended chemotherapy, osimertinib (80 mg once daily) was administrated to the patient. The lung tumor progressed after 1 month [Figure 1D]. Systemic therapy with carboplatin and pemetrexed was performed and a stable disease was reached after 2 months of the treatment. However, disease progressed after 4 months [Figure 1E], and the patient’s Eastern Cooperative Oncology Group (ECOG) performance status (PS) decreased to grade 4. NGS with serum was done and the MAF ofEGFRexon 21 L858R mutation increased to 5.5%;METamplification with a copy number of 3.1 was also found. Considering the patient’s critical ill condition, re-biopsy was unavailable andMETamplification was not re-confirmed by immunohistochemistry or fluorescencein situhybridization. A combinatorial treatment, consisting of crizotinib (250 mg twice daily) with first-generationEGFR-TKI erlotinib (150 mg once daily), was administrated. The patient’s ECOG score improved to 2; and the primary lung tumor decreased by 51% in length [Figure 1F]. The patient also obtained significant improvement in symptoms such as cough, dyspnea, and appetite. His disease was under control for 2 months at the last follow-up visit. The side effect was mild acne and anorexia. No diarrhea, pneumonitis, or transaminitis happened.

To the Editor:With the advancement of laparoscopic techniques, minimally invasive surgery is more widely applied in various conditions. The guidelines, published by the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) in 2017, considered that laparoscopic surgery could be safely performed at any stage of pregnancy, although best in mid-term.^[1]Since 2004, our team has carried out more than 150 laparoscopic procedures in pregnant patients who wanted to preserve their pregnancy. However, only six of these cases were in the late-term. Here we report a case of right ovarian cyst torsion successfully treated by laparoscopic oophorocystectomy in a patient at 35 weeks gestation. Following this operation, a healthy female of 3000 g was delivered at 40⁺²weeks gestation.

Following the original article’s publication,^[1]the authors informed us of the following errors.