Volume 103 ·  Issue 02 ·  2023

In August 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) jointly issued the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension, which updated the hemodynamic diagnostic criteria for pulmonary hypertension, causing widespread debate among experts. How should we respond to the updated diagnostic criteria for pulmonary hypertension? This paper analyzes the origin of the diagnostic criteria for pulmonary hypertension, how to understand the newly revised diagnostic criteria for hemodynamics, the definition of the new criteria for exercise pulmonary hypertension, and the important impact of the new diagnostic criteria on clinical practice, and puts forward countermeasures.

Early comprehensive assessment and early intervention of vascular disease, and the life-time maintenance of vascular health are the key to effectively preventing death and disability in end-stage of heart, brain, kidney and peripheral vascular events. Based on this concept, it is necessary to establish a professional clinical discipline of "vascular medicine" which is based on the systemic vascular bed, with measures on prevention, treatment, rehabilitation and intellectualized and digital vascular health management throughout the life cycle for different vascular lesions and different degree of vascular injury. The aim of the establishment of Beijing Vascular Health Stratification (BVHS) is to give a comprehensive and dynamic assessment of vascular health based on the concept of vascular medicine, to conduct individualized analysis of the results, to classify the degree of injury on vascular structure and function, to carry out individualized intervention, and eventually achieve targeted precise prevention and management, establish newly intellectualized and digital vascular health management medical model in China, for effectively reducing the incidence of cardiovascular events.

Androgen deprivation therapy is widely regarded as the first-line therapy for advanced prostate cancer. Although the initial efficacy is significant, clinical complications that arise after the therapy can reduce the patient′s life quality, affect the efficacy, and even endanger their health or life due to the progression to castration-resistant prostate cancer (CRPC). The gut microbiota is associated not only with local diseases of the intestinal tract but also with systemic diseases such as liver or neurological diseases, but its relationship with prostate cancer is less frequently studied. Androgen deprivation therapy for prostate cancer affects the gut microbiota of prostate cancer patients, thereby inducing relevant complications and promoting CRPC formation. In this review, we present the microecological effects of androgen deprivation therapy for prostate cancer on gut microbiota from the perspectives of gut microbiota diversity, intestinal microbiota structure, and functional pathways. We also propose corresponding countermeasures, such as fecal microbiota transplantation, oral antibiotics, and oral probiotics, to improve the efficacy and outcome of androgen deprivation therapy for prostate cancer by regulating gut microbiota, and provide new ideas for the diagnosis and treatment of advanced prostate cancer.

Cranio-orbital bone defects caused by various reasons may affect patients′ appearance, and even lead to severe complications. Herein, based on the clinical evidence level classification and recommendation level of the Evidence-based Medicine Center of Oxford University, domestic experts majoring in neurosurgery and ophthalmology learned from guidelines abroad and relevant evidence-based medicine, and repeatedly discussed the formulation of repair strategies and material selection for cranio-orbital defects caused by different reasons, covering the performance of various reconstruction materials, the selection and application of materials in different diseases and circumstances, material-related complications and other issues. Finally, the modified Delphi method was used to recruit experts′ suggestions, and 23 consensus recommendations were formulated in three aspects, thereby providing scientific and practical clinical guidance for the standardized diagnosis and treatment of cranio-orbital reconstruction and repair.

Recurrent implantation failure (RIF) is a challenging clinical problem. Although in vitro fertilization-embryo transfer technology has made remarkable advances, RIF remains a significant obstacle to achieving a successful pregnancy. A unified criterion of diagnosis and treatment for RIF has yet to be created. The etiology of RIF is complicated, including maternal, male, and embryonic factors. Maternal factors include dysimmunity, prethrombotic state, poor endometrial receptivity, infection, anatomical abnormalities, and endocrine disorders. The complexity and diversity of etiologies of RIF require clinicians to individualize the strategy of diagnosis and treatment for RIF patients. This consensus will provide the most relevant evidence to date for the examination, evaluation, and management of RIF, provide a reference for clinicians to make decisions, and standardize the diagnosis and treatment of RIF.

To investigate the efficacy of stent placement in the treatment of malignant tracheoesophageal fistula (MTEF) and the factors affecting the closure of the fistula.

Clinical, pathological, laboratory, and imaging data of 288 patients with MTEF admitted to Zhongda Hospital, Southeast University from 2015 to 2021were retrospectively analyzed. Among them, there were 208 males; the age was (63.6±10.5) years. A total of 94 patients received conservative treatment (conservative group), and 194 in the stent group (170 cases with esophageal stents and 24 cases with tracheal stents). Patients were followed-up at 2 weeks, 1 month, 3 months, and 6 months to evaluate the effect of stent implantation. Multivariable logistic regression was used to analyze factors affecting fistula closure.

Age, fistula size, leukocyte count before treatment, and fistula location were significantly different between the conservative group and the stent group (P<0.05). The Karnofsky functional status (KPS) score before treatment in the conservative group was lower than the stent group, (45.1±1.0) vs (51.8±0.7) scores, respectively (P<0.001). After 2 weeks and 1 month of treatment, improvement in KPS scores was significantly better in the stent group than in the conservative group (P<0.05). At 1 month, the pulmonary infection rate in the stent group was 33.5% (58/173), significantly lower than that in the conservative group [77.0% (47/61); P<0.001]. Among the 288 patients, the fistula was closed in 196 patients and unclosed in 92 patients. Fistula size (OR=3.429, 95%CI: 1.623-7.829, P=0.001), leukocyte count before treatment (OR=1.160, 95%CI: 1.027-1.317, P=0.018), KPS score before treatment (OR=0.898, 95%CI: 0.848-0.945, P<0.001) and the treatment method (conservative treatment as reference, esophageal stent OR=0.010, 95%CI: 0.004-0.030, P<0.001; tracheal stent OR=0.003, 95%CI: 0.000-0.042, P<0.001) were factors affecting fistula closure. In the 170 patients in the esophageal stent group, early complications (≤24 h) occurred in 71 patients, and late (>24 h) complications occurred in 11 patients. While in the 24 patients in the tracheal stent group, 9 had early complications and 2 had late complications.

Stent placement is an effective treatment for MTEF compared to conservative treatment. Stent treatment, small fistula size, low pre-treatment leukocyte count, and high pre-treatment KPS score are beneficial to fistula closure.

To investigate the efficacy of sacubitril/valsartan in peritoneal dialysis (PD) patients with heart failure with preserved ejection fraction (HFpEF) and its effect on residual renal function.

PD patients with HFpEF in Ningbo First Hospital from March 2018 to August 2021 were retrospectively enrolled and divided into study group with sacubitril/valsartan and control group with valsartan. The clinical baseline data before treatment and clinical indicators during follow-up (6 and 12 months after treatment) were collected and compared between the two groups, and the adverse reactions were also recorded.

A total of 99 patients were included in the study. There were 61 patients in the study group, including 44 males and 17 females, with a mean age of (52±13) years. Meanwhile, there were 38 patients in the control group, including 23 males and 15 females, with a mean age of (57±14) years. There was no statistically significant difference in clinical baseline data between the two groups (e.g., age, sex, body mass index, duration of dialysis) (all P>0.05). The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular end-systolic dimension (LVDs) were lower, but the left ventricular ejection fraction (LVEF) was higher in the study group than those in the control group at 6 and 12 months after treatment (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were lower than baseline values at 6 and 12 months after treatment respectively, with statistically significant differences (all P<0.05). However, there were no statistically significant differences in the decreases of SBP and DBP between the two groups at 6 and 12 months after treatment (all P>0.05). The decrease extents in residual estimated glomerular filtration rate (eGFR) [0.52 (-0.05, 1.19) vs 1.72 (0.97, 2.39) ml·min^-1·(1.73 m²)^-1, P<0.001]and 24-h residual urine volume [200 (-100, 300) vs 300 (137, 400) ml, P=0.018] at 12 months after treatment were lower in the study group than those in the control group. During the follow-up period, hyperkalemia occurred in 16 cases (26.2%) and 13 cases (34.2%) in the study group and the control group, and hypotension occurred in 3 cases (4.9%) and 1 case (2.6%) in the study group and the control group, respectively. There were no adverse reactions such as cough and angioneurotic edema in the two groups.

Sacubitril/valsartan can safely and effectively improve cardiac function and lower blood pressure in PD patients with HFpEF. Compared with valsartan, sacubitril/valsartan may be more beneficial to delay the loss of residual renal function in PD patients with HFpEF.

To investigate the incidence, risk factors, and outcomes of hyperlactatemia after pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest (DHCA).

From December 2016 to January 2022, patients receiving PEA in China-Japan Friendship Hospital were enrolled in the study. Arterial blood samples were analyzed intraoperatively. Multivariate logistic regression analysis was performed to identify the predictors of intraoperative lactate elevation as well as major factors influencing the clinical outcome of the surgery.

A total of 110 patients (69 males and 41 females) were enrolled, aged (50.6±12.8) years. Receiver operating characteristic curve yielded an optimal cut-off lactate level of 7 mmol/L for predicting major postoperative complications (re-operation, re-intubation, postoperative renal failure requiring renal replacement therapy, wound infection, stroke, atrial fibrillation, and perioperative extracorporeal membrane oxygenation usage within 48 hours after surgery). Thirty-nine patients (35.5%) had an intraoperative peak arterial lactate level of≥7 mmol/L. According to intraoperative peak arterial lactate level, the patients were divided into two groups (<7 mmol/L and≥7 mmol/L). There were no statistically significant differences in age, sex and body mass index between the two groups (all P>0.05). Intraoperative peak lactate level was associated with prolonged mechanical ventilation time (r=0.262, P=0.008) and intensive care unit length of stay (r=0.304, P=0.002). Multivariate logistic regression analysis identified three key variables associated with lactate level≥7 mmol/L: DHCA duration (OR=1.186, 95%CI: 1.027-1.370, P=0.020), nadir hematocrit (HCT) (OR=0.580, 95%CI: 0.341-0.988, P=0.045) and preoperative pulmonary vascular resistance (PVR) (OR=1.096, 95%CI: 1.020-1.177, P=0.012). Patients with lactate≥7 mmol/L carried a higher rate of major complications (P=0.001). For patients with lactate≥7 mmol/L, 41.0% (16 out of 39 cases) had major complications, while for patients with lactate<7 mmol/L, only 14.1% (10 out of 71) had major complications. There was no statistically significant difference in mortality (8.5% vs 10.3%, P=0.753) between patients with different lactate levels. Moreover, intraoperative peak lactate level was a predictor of postoperative combined morbidity (OR=1.625, 95%CI: 1.176-2.245, P=0.003).

High intraoperative lactate levels are associated with higher preoperative PVR, lower nadir HCT, and longer DHCA duration. Intraoperative lactate levels are independently associated with increased combined morbidity.

Pulmonary lymphangiomyomatosis (PLAM) is a low-grade malignant neoplastic disease that occurs in women of childbearing age. The lack of effective animal models has been the bottleneck of its mechanism research. Existing PLAM animal models include transplanted tumor mouse models injected with tuberous sclerosis complex gene 2 (TSC2) -deleted tumor cells, wherein the transplanted tumor mouse models include allogeneic transplanted tumors, humanized xenograft tumors, and rat-derived xenograft tumors, and transgenic mouse models include germline knockout and conditional knockout mice. Some PLAM animal models have PLAM-like lung lesions, which are mainly used to find new therapeutic targets of PLAM and sources of PLAM tumor cells, but they cannot fully represent the disease development of PLAM patients. This paper summarizes the characteristics and clinical application of all PLAM animal models at present, and analyzes the research progress in recent 6 years based on the author's research experience, so as to provide reference for scholars in this field.

Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by multiple etiologies and pathogenesis, with complex pathogenesis, and the gold standard for its diagnosis is the invasive manipulation of the right cardiac catheter. The non-invasive auxiliary diagnosis technology of artificial intelligence (AI) relies on image analysis, which is the first choice target for its application in the medical field. At present, it has made staged achievements in the research fields of diagnosis of PH such as chest X-ray, echocardiography, CT and MRI. The integration of AI and medicine has brought revolutionary changes to medical services and medical research, and is the future development direction of medicine. The application of AI in non-invasive auxiliary diagnosis of PH will surely improve the efficiency of diagnosis and treatment and reduce the economic burden of patients. Therefore, the purpose of this paper is to review recent research on AI in the field of pH-assisted diagnosis and promote its application in clinical diagnosis and scientific research.

Meibomian gland dysfunction (MGD) is a chronic, diffuse meibomian gland lesion characterized by obstruction of the meibomian gland terminal duct and/or abnormal quality or quantity of meibomian lipid secretion. At present, the conventional treatment methods of MGD have certain limitations. As a new macrolide antibacterial drug, azithromycin has the characteristics of long half-life, good intraocular permeability and wide antibacterial range. At present, a number of clinical trials have confirmed the advantages and effectiveness of topical azithromycin in the treatment of MGD. This article reviewed the drug characteristics, mechanism of action, efficacy and safety of azithromycin in topical application to MGD, and deeply understood the new progress of azithromycin in the treatment of MGD.

Lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by cystic lung destruction, progressive lung function decline, and lung failure. The pathology of LAM is characterized by the hyperproliferation of abnormal smooth muscle-like LAM cells in the lung, and the abnormal expression of multiple proteases [mainly matrix metalloproteinase-2 (MMP-2), MMP-9 and cathepsin K] in LAM cells, which may directly lead to lung structural destruction and cyst formation. Rapamycin is the primary treatment for patients with LAM, but the disease continues to progress after discontinuation. At present, pulmonary function tests [such as forced expiratory volume in the first second (FEV1)] are the standard method for monitoring the burden of disease and treatment response in patients with LAM. However, FEV1 levels are prone to technical variations and the response to treatment is slow, so quantitative, accurate and rapid-response biomarkers are urgently needed to monitor disease progression and treatment prognosis in patients with LAM. Activity-based nanosensors are emerging biosensors that detect dysregulated proteases in the body and release a reporter to provide urinary readings of disease. Due to the widespread dysregulation of protease regulation in LAM, this study developed a nanosensor panel containing 14 peptide substrates, which was tracheally instilled into the lungs of LAM model mice, and urine was collected for mass spectrometry to determine the nanosensor cleavage products, monitoring the response of LAM mice to rapamycin treatment, and distinguishing healthy from LAM mice, treated from untreated mice through machine learning. It was found that the multiactivity-based nanosensor PP03 (cleaved by MMP, aspartic acid and cysteine proteases) (P<0.001) and PP10 (cleaved by serine, aspartate and cysteine proteases) (PThe cleavage signal of =0.017) is significantly different between LAM mice and normal mice, and the machine learning model can be strongly classified. Within 2 d after rapamycin treatment, the cleavage signals of PP03 and PP10 returned to normal in LAM mice, and the machine learning model enabled accurate classification of treatment response [area under the curve (AUC) =0.94 in the untreated group].

Lymphangioleiomyomatosis is a multisystem disease that causes cystic changes in the lungs and respiratory failure. The loss of 1/2 gene function in tuberous sclerosis (TSC) leads to dysregulation of mammalian rapamycin target protein (mTOR) activity and hyperproliferation of abnormal smooth muscle cells (i.e., LAM cells). LAM cells interact with fibroblasts, lymphoendothelial cells, and various inflammatory cells to form LAM nodules similar to "cancer nests" in the lungs. In addition, mast cell aggregation was also found in LAM nodules, but its function and mechanism are still unclear. Mast cells are granular hematopoietic cells that reside in tissues and play a key role in the pathological processes of allergy, asthma, fibrosis and arthritis. Trypsins are serine proteases, which are one of the most secreted substances by mast cells and act as fibroblast mitogens in lung diseases. This study analyzed the interaction between LAM cells and LAM-associated fibroblasts (LAF), evaluated the relationship between LAM cells and mast cell migration through 3D spheroid co-culture, and constructed LAM mouse allogeneic transplantation tumor model to explore the effect of mast cells and their trypsin secreted on LAM. It was found that LAM cells/LAF co-culture induced LAF to secrete multiple CXC chemokines, and the number of trypsin-like mast cells expressing CXC chemokine receptors (CXCRs) in LAM lungs was significantly increased (P<0.05）。 LAM spheroids attract mast cells, a process inhibited by pharmacology of CXCR1 and CXCR2 and CRISPR/cas9 inhibition. LAM spheroids caused mast cell trypsin-like release, induced fibroblast proliferation, and increased LAM spheroid size (P=0.002）； Trypsin-like inhibitors APC366 and sodium tryptonate (SCG) inhibit mast cell-induced spheroid growth. In vivo, SCG reduced mast cell activation and lung tumor burden in LAM mice (P=0.004）。