Volume 101 ·  Issue 20 ·  2021

Interstitial lung disease (ILD), consisting of more than 200 subtypes of diseases, is a large group of heterogeneous diseases characterized by varying degrees of alveolitis and pulmonary parenchymal fibrosis. There are many challenges in its diagnosis and treatment. In recent years, new understanding of the clinical classification, disease behavior, early diagnosis, and treatment of ILD has been obtained. The anti-fibrotic drugs have been expanded successfully from treatment of idiopathic pulmonary fibrosis (IPF) to progressive-fibrosing interstitial lung diseases (PF-ILD). A new international clinical practice guideline categorized hypersensitivity pneumonitis (HP) into two clinical phenotypes, namely nonfibrotic and fibrotic HP. The clinical classification of ILD according to disease behavior and a progressing fibrotic phenotype is of important value for the establishment of treatment strategies for patients with ILD. Interstitial pulmonary abnormalities (ILA) may represent the subclinical stages of different types of ILD, and long-term follow-up of ILA is key to improving the early diagnosis of ILD. Interstitial pneumonia with autoimmune features (IPAF) may represent an early phase or prodromal state of a connective tissue disease (CTD), and patients with IPAF need to be under longitudinal surveillance for evolution to CTD.

Since the discovery of Epstein-Barr (EB) virus from the cultured cells in Burkitt lymphoma tissue in African children in 1964, we have gradually taken in its oncogenicity and the link between this virus and multiple mucocutaneous diseases. This review exhibits the process of EB virus infection and summarizes the clinical manifestations and varied prognosis of EB virus-associated skin diseases. The cases of common skin diseases including psoriasis, dermatomyositis, pemphigus, pemphigoid, parapsoriasis, atopic dermatitis, urticaria, systemic lupus erythematosus, scleroderma, panniculitis,erythema multiforme and vasculitis coinciding with EB virus infection were collected for the analysis of their EB virus-associated complications, treatments and outcomes.

This guide was jointly prepared by a writing committee composed of nephrology and blood purification experts. It systematically introduces the etiology and pathogenesis, diagnosis and disease assessment, treatment principles, targets and specific programs, treatment of hyporesponsiveness and diagnosis and treatment of anemia in patients with special kidney diseases. This guide aims at six main clinical problems, such as how to standardize the diagnosis of renal anemia, the timing and target of erythropoiesis stimulator (ESAs) application, how to evaluate iron status and the timing and target of iron application, the anemia treatment plan of non-dialysis, hemodialysis and peritoneal dialysis patients, the anemia treatment plan of kidney transplant, children, elderly and diabetic patients, and how to standardize the application of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). The aim is to guide and standardize the diagnosis of renal anemia and the rational application of ESAs, iron and HIF-PHI, so as to improve the diagnosis and treatment level of renal anemia.

Because dopamine drugs can effectively increase cardiac output, increase blood pressure and increase blood perfusion of internal organs such as kidneys, they are often widely used as first-line emergency drugs in the treatment of various types of shock, heart failure and acute kidney injury in China, as well as the maintenance of perioperative blood pressure. In order to help the majority of clinical workers use dopamine reasonably and standardizedly, the author wrote this expert consensus according to the latest clinical research results at home and abroad, referring to relevant guidelines, combining with China's national conditions and clinical practice. The pharmacological characteristics, clinical research evidence, indications, clinical use methods and adverse drug reactions of dopamine were comprehensively introduced.

To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism.

From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared.

All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients.

Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

To investigate the changes of interleukin-35 (IL-35) level and CD14⁺monocytes function in patients with chronic heart failure (CHF).

A total of 74 patients with CHF who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Zhengzhou University between July 2018 and June 2019 as well as 29 healthy controls (HC) were continuously enrolled. 20 ml fasting anticoagulant peripheral blood was collected in the morning, and plasma was separated. IL-35 level was measured by ELISA. Peripheral CD14⁺monocytes were purified, and the IL-35 receptor subunits (IL-12Rβ2 and gp130 mRNA) relative levels were semi-quantified by real-time PCR. CD14⁺monocytes were stimulated with IL-35, and were cultured in direct contact or indirect contact with human umbilical vein endothelial cells (HUVEC). Cytokines and granzyme B secretion in the supernatants was measured by ELISA. The percentage of HUVEC death was calculated by measuring lactate dehydrogenase level. The difference of the above indicators were compared between the CHF group and the HC group.

The age for the CHF group was (59.4±12.1) years, and 58.1% (43 cases) of them were males. The age for the HC group was (53.9±9.8) years, and 65.5% (19 cases) of them were males. The plasma IL-35 level was higher in the CHF group than the HC group ((22.89±7.58) mg/L vs (16.42±5.47) mg/L, P<0.001). The gp130 mRNA relative level was also higher in the CHF group than the HC group (1.07±0.19 vs 0.98±0.15, P=0.022). CD14⁺monocytes induced HUVEC death in the CHF group was lower in both direct contact and indirect contact culture system than the HC group (both P<0.001). The granzyme B secretion was also lower in the CHF group than the HC group (P<0.001). The CD14⁺monocytes induced HUVEC death was down-regulated in response to granzyme B inhibition (P=0.011). Both the CD14⁺monocytes induced HUVEC death and the granzyme B secretion were reduced in response to IL-35 stimulation (both P<0.001).

CHF patients have the elevated IL-35 expression. IL-35 induces CD14⁺monocytes dysfunction via the inhibition of granzyme B secretion. This process promoted the progression of heart failure.

To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease.

We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected.

PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) μmol/L、(10.0±1.0) μmol/L、(11.7±1.0) μmol/L vs (4.2±1.8) μmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) μg/L、(1.64±0.27) μg/L、(1.20±0.14) μg/L vs (2.62±0.12) μg/L, allP<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(allP<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) μg/L vs (3.03±0.10) μg/L、(2.06±0.05) μg/L vs (2.31±0.06) μg/L、(1.83±0.07) μg/L vs (1.96±0.11) μg/L、(1.20±0.06) μg/L vs (1.39±0.09) μg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) μg/L vs (0.59±0.09) μg/L、(0.62±0.04) μg/L vs (0.53±0.05) μg/L、(0.55±0.14) μg/L vs (0.51±0.12) μg/L、(0.48±0.12) μg/L vs (0.35±0.08) μg/L] in response to different treatments in cultured H9c2 cardiomyocytes (allP<0.05).

PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.

To investigate effect of Bimatoprost (BimP) on growth of reconstructed hair follicles in recipient nude mice.

Primary epidermal and dermal cells were isolated from newborn C57BL/6J mice (1-day-old) skins, and the reconstructed hair follicles was implanted in the dorsal skin of Balb/c-nu nude mice using a silicon chamber protocol, then, the 18 nude mice were randomly divided into control group, BimP group and minoxidil group, with 6 mice in each group. After 2 weeks, topical treatment was applied to the grafted area of the nude mice by 2% minoxidil 100 μl, 0.03% BimP 100 μl and saline 100 μl, respectively, once daily for 2 weeks. At day 14 after treatment, the mice were euthanized to measure the length of dorsal hair, and the number and hair cycle of the reconstructed follicles was observed histologically. The total mRNA and proteins expression of Wnt3a, LEF1, β-catenin and Frizzled7 were determined by qPCR and Western Blotting. The distribution and expression of β-catenin in the reconstructed follicles was detected by immunofluorescence staining.

As compared to the control group, the BimP group had thicker and longer hair [(0.57±0.07) vs (0.36±0.05) cm, P<0.01], no significant difference was seen between the BimP and minoxidil group. The mRNA expression levels of Wnt3a (2.73±0.17 vs 1.00±0.14,P<0.01)、LEF1(1.71±0.12 vs 1.00±0.19,P<0.01)、β-catenin (2.37±0.21vs 1.00±0.11,P<0.01) and Frizzled7 (2.62±0.15vs 1.00±0.18,P<0.01) were significantly increased in BimP group compared with the control group. Western Blotting showed the same results, the protein expression levels of Wnt3a (1.44±0.21vs 1.00±0.13,P<0.05)、LEF1 (1.36±0.15 vs 1.00±0.09,P<0.05)、β-catenin (1.60±0.13 vs 1.00±0.16,P<0.01) and Frizzled7 (1.52±0.15 vs 1.00±0.21,P<0.05) in BimP group were higher than those in control group, and the difference was statistically significant. Immunofluorescence staining showed that β-catenin was strongly expressed in hair bulb cells and sebaceous gland cells of reconstructed hair follicles in BimP group and minoxidil group, whereas barely seen in the control group.

BimP directly promotes growth of reconstructed hair follicles in mice by activating canonical Wnt/β-catenin signaling pathway.

Reports1A case of neurofibromatosis type I complicated with primary neuroendocrine tumor of the liver. The patient was a 47-year-old male with a history of type I neurofibromatosis for more than 20 years. The patient was unexpectedly found to occupy the liver two years ago, and during the follow-up, the mass gradually increased. CT examination showed low-density masses in liver IV and VIII segments; MRI showed a slightly longer T₁Non-uniform length T₂Signal and enhancement scan showed progressive continuous obvious enhancement; The final pathological diagnosis was a neuroendocrine tumor of the liver.

The identification of medical fault is the core element of the establishment of medical tort liability. Common medical faults include medical ethics faults, medical technology faults, medical record writing/keeping faults and organization and coordination faults, and it is necessary to discuss them in a typical manner. In practice, there are deviations in the judicial application of medical fault determination rules, which are mainly reflected in: vague medical level determination standards, absolute application of diagnosis and treatment norms, disputes over the exemption reasons for medical fault, and judicial excessive reliance on medical damage identification opinions, etc. The following paths should be followed to improve the rules for determining medical fault: clarify the standard of "rational doctor" for judging medical level; Restrict the scope of legal diagnosis and treatment norms and exclude their absolute applicability; Standardizing the reasons for exemption of medical fault, recognizing the exemption of emergency medical measures, and paying attention to the individual differences of patients; Treat medical damage appraisal opinions prudently, and make it clear that they can only be used as auxiliary evidence for case judgment.

Thyroid autoimmunity is characterized by positive thyroid autoantibodies and is a common disease in women of childbearing age. In recent years, the results of studies on thyroid autoimmunity and pregnancy outcomes have been controversial. Therefore, this article reviews the effects of thyroid autoimmunity on the pathophysiology of female reproductive system, adverse pregnancy outcomes, assisted reproductive outcomes, and whether levothyroxine supplementation can improve pregnancy outcomes in infertile women with thyroid autoimmunity.

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive tumor derived from mesenchymal tissue. At present, the efficacy of chemotherapy and immunotherapy for MPM is not good. It has become one of the hot spots in the research field of MPM therapy to explore immune markers that can effectively and accurately guide the treatment and predict the prognosis, and explore potential new immunotherapy targets. Recent studies have found that MPM has a suppressive tumor immune microenvironment. Tumor infiltrating lymphocytes (TIL), as an important component of tumor immune microenvironment, also participate in immune regulation. However, the current research conclusions on the effect of TIL on the therapeutic effect and prognosis of MPM are not uniform. Therefore, this article reviews the effect of TIL on chemotherapy and immunotherapy effects of MPM, and the effect of TIL on the prognosis of MPM patients.

It has been speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support this speculation. The study hypothesized that balanced anesthesia combined with dexmedetomidine reduced postoperative opioid-related adverse events compared to balanced anesthesia with remifentanil. In this single-blind randomized controlled study, patients undergoing medium to large non-cardiac surgery from 10 centers in France were randomly assigned to remifentanil plus morphine (remifentanil) and dexmedetomidine (opioid-free). All patients received intraoperative analgesia with propofol, desflurane, dexamethasone, lidocaine, ketamine and muscle relaxants, and postoperative analgesia with lidocaine, paracetamol, nefopam and patient-controlled morphine. The primary outcome measure was the occurrence of opioid-related adverse events (hypoxemia, intestinal obstruction, or cognitive dysfunction) within 48 h after extubation. Secondary measures included postoperative opioid consumption, pain, and the occurrence of nausea and vomiting. The results showed that the study was discontinued prematurely due to severe bradycardia in 5 patients in the opioid-free group. Compared with 105 of 156 patients (67%) in the remifentanil group, the primary outcome event occurred in 122 of the opioid-free patients (78%) (RR=1.16，95%CI：1.01~1.33，P=0.031)。 The incidence of hypoxemia was 72% (110/152) in the opioid-free group and 61% (94/155) in the remifentanil group (RR=1.19，95%CI：1.02~1.40，P=0.030)。 There was no significant difference between the two groups in terms of intestinal obstruction or cognitive dysfunction. Cumulative morphine dosage [11 (5, 21) mg vs. 6 (0, 17) mg] and incidence of nausea and vomiting (37% vs. 24%,RR=0.64，95%CI: 0.45~0.90) were both less, but the analgesic effects were similar in the two groups. Patients in the opioid-free group had a longer delay in extubation and a longer stay in the recovery room after anesthesia. Opioid-free balanced anesthesia with dexmedetomidine did not reduce the occurrence of postoperative opioid-related adverse events compared with remifentanil. On the contrary, it results in a higher incidence of serious adverse events, particularly hypoxemia and bradycardia.

A formula based on serum creatinine (Scr) is commonly used to estimate glomerular filtration rate (eGFR) in daily clinical practice. The most commonly used formulas are the Childhood Chronic Kidney Disease Study (CKiD) formula, and the Adult Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, both of which are currently recommended by authoritative guidelines in the field of kidney disease. However, both formulas have certain limitations, and when patients transition from adolescence to adulthood, applying these two formulas at the same time will lead to large differences in the estimated eGFR results. The full-age spectrum (FAS) formula overcomes this problem, but will overestimate the eGFR of patients with low Scr values and chronic kidney disease. Based on the above status quo, the overall goal of this study is to develop and validate a new SCR-based formula that can be applied to all ages and different renal functions, combining the characteristics of FAS and CKD-EPI formulas. The investigators used 19 629 patient data from 13 cohorts for formula development and internal and external validation. Seven of these cohorts (n=11 251) were randomized to develop (n=8 473) and internal validation (n=2 778) dataset, and the remaining 6 cohorts (n=8 378) for external verification. After absorbing the advantages of the FAS and CKD-EPI formulas, the basic form of the new formula was firstly determined: eGFR = A × (Scr/Q)^B× [C^(Age-AgeCO)if Age>AgeCO]. Where a, B, C are unknown parameters, where B is in Scr/Q<Take different values when 1 and ≥1, respectively, C^{(Age-AgeCO) is}The age term in the formula, AgeCO represents the cut-off value of age. The Q value (median of Scr) in the formula was taken from a recent study. Multivariate linear regression was used to compare the results from 3 European hospitals (n=83 157, aged 2 to 40 years), and the relationship between Q and Age can be obtained: Men aged 2 to 25 years: ln (Q) =3.200+0.259× Age-0.543× ln (Age) -0.007 63× Age²+0.000 079× Age³； Females 2-25 years old: ln (Q) =3.080+0.177× Age-0.223× ln (Age) -0.005 96× Age²+0.000 068 6× Age³； Male>25 years old: Q =80 μ mol/L; Women>25 years old: Q =62 μ mol/L. The basic form of the new formula is logarithmically transformed and fitted by least squares linear regression method to obtain the unknown parameters in the formula. The study retained a =107.3 and AgeCO =40 in the FAS formula, and then pooled the development and internal validation datasets to determine the final new formula, which was named the EKFC formula: age 2~40 years, Scr/Q<At 1, eGFR =107.3× (SCr/Q)^-0.322When Scr/Q ≥1, eGFR =107.3× (Scr/Q)^-1.132； Age>40 years, Scr/Q<At 1, eGFR =107.3× (SCr/Q)^-0.322×0.990^(Age-40)When Scr/Q ≥1, eGFR =107.3× (Scr/Q)^-1.132×0.990^(Age-40)。 The study proposes a new formula that combines the advantages of the FAS and CKD-EPI formulas, thereby generally reducing bias in different age and renal function populations, and the EKFC formula has higher accuracy and precision than the currently recommended formulas, enabling continuity across the entire age range, avoiding transition problems between adolescent and adult eGFR.