Volume 101 ·  Issue 10 ·  2021

Diabetic kidney disease (DKD) has emerged as the primary cause of chronic kidney disease, posing a huge economic and social burden. Therefore, it is urgent to strengthen the prevention and treatment of DKD. However, due to the complex pathogenesis of DKD and the lack of specific and effective intervention targets, there is currently no breakthrough in treatment, thereby causing the continuous increase of end-stage DKD. This review examines several key nodes in the progress of DKD treatment, in order to standardize the clinical treatment, promote the research progress, and improve the prognosis of DKD.

Chronic kidney disease (CKD) in diabetes mellitus includes diabetic kidney disease (DKD), non-diabetic kidney disease (NDKD) or a combination of NDKD and DKD. The clinical and renal pathological manifestations of DKD in type 1 diabetes are different from those in type 2 diabetes. Renal biopsy histopathology is the gold standard for distinguishing DKD from NDKD. However, based on the same pathological diagnosis, DKD patients may still have different disease progression and prognosis due to individual differences in molecular biological mechanisms. Metabonomics, proteomics, transcriptomics and artificial intelligence offer hope for biomarkers to diagnose and predict the progress of DKD.

Diabetic kidney disease (DKD) is the most common chronic complication of diabetes mellitus and the major cause of end stage renal disease (ESRD). Prediction, early diagnosis and evaluation of disease progression are crucial to improve the prognosis of DKD. Estimated glomerular filtration rate (GFR) and urinary albumin excretion rate (AER) are the main diagnostic biomarkers of DKD. However, the sensitivity and specificity are insufficient. In recent years, more and more attention has been paid to the value of novel biomarkers of DKD. This article reviews the clinical studies of novel biomarkers of DKD, in order to provide reference for clinical diagnosis and prognosis evaluation of DKD.

COVID-19 is an important public health issue of great concern at home and abroad, and it is still in the state of global pandemic. During the normalization stage of prevention and control of the epidemic of COVID-19, China effectively controlled the outbreak and spread of the epidemic by adopting the strategy of "import of external prevention and rebound of internal prevention", and effectively reduced the occurrence of death cases. The social economy recovered quickly, and various measures were highly recognized by the public, and the positive trend of the epidemic continued to consolidate. At present, although the spread of the local epidemic has been basically stopped, the international epidemic continues to rise rapidly, and the pressure of "imported prevention and control" in China continues to increase. Considering the characteristics of the normalization of epidemic prevention and control and the particularity of the virus, the connotation of the normalization of epidemic prevention and control should be understood scientifically. The prevention and control goal of the epidemic in the normalization stage should be to maximize early detection, early treatment and early disposal, and resolutely prevent the continuous spread of the epidemic in communities, that is, to prevent the infection as much as possible, and resolutely prevent the rebound (sustained spread in communities), rather than "zero infection". The prevention and control policy of "timely detection, rapid disposal, precise management and control, and effective treatment" has been implemented in various localities, and a series of effective and regular experience in prevention and control has been formed in the practice of prevention and control. Winter and spring are the key periods for the prevention and control of the epidemic. We should continue to work together to prevent and control the epidemic, fulfill the responsibilities of all parties, and prevent and control the epidemic in a scientific and effective way.

The incidence and mortality of pancreatic cancer are increasing year by year worldwide, but the prevention and treatment effect is far from satisfactory. Surgical resection remains the main treatment for pancreatic cancer, but the advantages and disadvantages of surgery are clear. How to avoid the disadvantages and maximize the advantages of surgery to optimize the benefits of patients contributes the main criteria for judging whether the operation for pancreatic cancer is successful or not. In order to achieve the success of pancreatic cancer surgery, perioperative attention must be paid to the comprehensive factors including tumor, host and surgical team, especially to fully understand the limitation of TNM staging,and to emphasize the individualized comprehensive diagnosis and treatment protocol under the guidance of standardized multidisciplinary team (MDT) mode, with long-term survival as the ultimate goal of being a qualified surgical oncologist.

In recent years, more and more attention has been paid on the role of neoadjuvant therapy in the comprehensive treatment of pancreatic cancer. There is increasing evidence indicates that neoadjuvant therapy improves the R0 resection rate and patient′s prognosis. However, the indication, therapy selection and efficacy evaluation of neoadjuvant therapy in patients with pancreatic cancer are still controversial, thus its clinical application is not very mature. This article aims to analyze the clinical implementation dilemma of neoadjuvant therapy for pancreatic cancer, and discuss the scientific and reasonable neoadjuvant treatment mode for pancreatic cancer patients.

Pancreatic cancer is one of the most malignant digestive tract tumors with a 5-year survival rate of less than 10%. Surgery remains the basis of long-term survival of pancreatic cancer patients. With the progress of chemotherapy, neoadjuvant therapy has been gradually carried out in pancreatic cancer. There are more and more studies on the effects of neoadjuvant therapy on perioperative complications of pancreatic cancer, but the results are not consistent. This article reviews the recent studies on neoadjuvant therapy for pancreatic cancer and analyzes the impact of some key factors on perioperative complications.

Pancreatic cancer is considered to be the most malignant digestive tract tumor due to its high invasiveness, metastasis and recurrence rate. In recent years, neoadjuvant therapy has brought new insights to the treatment of pancreatic cancer. To date, the value of neoadjuvant therapy in pancreatic cancer has been widely recognized, but there is a lack of specific regimens. The superiority and inferiority of various regimens are still uncertain, therefore, the efficacy of neoadjuvant therapy can be evaluated combined with imaging, functional and biological markers.

Pancreatic cancer has a high degree of malignancy, with a poor prognosis. Although surgical resection remains the only way to cure pancreatic cancer at present, the treatment mode has changed from "surgery priority" to "multidisciplinary cooperation" with the development of adjuvant therapy. Neoadjuvant therapy has been documented to increase the R0 resection rate of borderline resectable and locally advanced pancreatic cancer and improve the prognosis of the patients, and there has been a consensus on neoadjuvant therapy for these patients. However, there is still much controversy in the choice of neoadjuvant chemotherapy, the status of radiotherapy, imaging and pathological evaluation after neoadjuvant therapy for pancreatic cancer.

To explore the relationship between platelet/lymphocyte ratio (PLR) and cognitive impairment (CI) in diabetic patients treated with maintenance hemodialysis (MHD).

The data of age, gender, underlying diseases, medication history, mini-mental state examination (MMSE) and biochemical indexes of diabetic MHD patients who were treated in 18 hemodialysis center in Guizhou Province between May and August 2019 were collected. According to whether they had CI or not, the patients were divided into CI group and control group, and the clinical characteristics between the two groups were compared. In addition, the patients were divided into four groups according to the quartile of PLR (PLR Q1, Q2, Q3 and Q4 group). Multivariate logistic regression models were used to analyze the relationship between PLR level and CI in diabetic MHD patients. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of PLR in detecting CI in diabetic MHD patients.

Totally, 586 diabetic MHD patients (389 males) were included, with a mean age of (63±11) years. Multivariate logistic regression analysis showed that PLR was associated with the risk of CI in diabetic MHD patients, and the risk of CI in PLR Q4 group was 3.022 times of that of PLR Q1 Group (95%CI: 1.866-4.895, P<0.001). After adjusting for gender, age, dialysis age and education level, the risk of CI in PLR Q4 group was 2.529 times of that in PLR Q1 Group (95%CI: 1.536-4.164, P<0.001). After further adjusting for hemoglobin, albumin, creatinine, leukocyte and blood glucose, the risk of CI in PLR Q4 group was 2.281 times of that in PLR Q1 group (95%CI: 1.203-4.326, P=0.012). ROC curve analysis showed that the optimal threshold for PLR to predict CI in diabetic MHD patients was 155.3, with a sensitivity of 57.2% and a specificity of 60.8%, and the area under the curve was 0.608 (95%CI: 0.561-0.644, P<0.001).

PLR is associated with CI in diabetic MHD patients.

To explore the effects and mechanisms of Xuezhikang on preventing contrast-induced nephropathy (CIN) in diabetic rats.

Streptozotocin (65 mg/kg) was injected intraperitoneally to establish a diabetes model in 7-week-old male Sprague-Dawley (SD) rats. After 4 weeks of modeling, 24 diabetic rats were randomly divided into 4 groups: sham group, CIN group, CIN+vehicle (Veh) group and Xuezhikang group. All animals were sacrificed at 24 hours after administration of contrast. Blood and kidney tissues were collected to detect biochemical, inflammation-related, oxidative stress-related and pathological indicators.

After administration of contrast agent, the renal function-related indicators were decreased in Xuezhikang group compared with CIN+Veh group [serum creatinine (SCr): (59.3±3.3) μmol/L vs (73.2±4.1) μmol/L; blood urea nitrogen (BUN): (13.8±0.5) mmol/L vs (16.3±0.6) mmol/L; serum neutrophil gelatinase-associated lipocalin (sNGAL): (41.4±2.0) ng/ml vs (54.9±4.4) ng/ml; urinary kidney injury moleculer-1 (uKIM-1): (11.1±0.5) ng/ml vs (16.6±0.5) ng/ml] (all P<0.05). Histological analysis showed that the severity of renal tubule dilatation, brush border loss and renal tubular cell necrosis in Xuezhikang group was better than that of CIN+Veh group. Additionally, the oxidative stress-related indicators of Xuezhikang group improved compared with those of CIN+Veh group [malondialdehyde (MDA): (12.1±0.7) nmol/mg vs (15.5±0.8) nmol/mg, superoxide dismutase (SOD): (35.0±2.2) U/mg vs (23.7±3.4) U/mg, renal nitrite: (1.7±0.1) nmol/mg vs (1.2±0.1) nmol/mg, allP<0.05]. Meanwhile, Xuezhikang pretreatment downregulated the mRNA and protein expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (bothP<0.05).

The current study suggests that Xuezhikang protects against CIN in diabetic rats by inhibiting oxidative stress and inflammation.

To uncover the role and mechanism of non-coding RNA-activated by DNA damage (NORAD) in proliferation and apoptosis of mouse mesangial cells induced by high glucose.

SV40-MES-13 cells were divided into high glucose group and low glucose group according to the concentration of glucose in the culture medium. After 24 hours of treatment, SV40-MES-13 cells were transfected with si-NORAD and si-Toll-like receptor (TLR4), and real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of NORAD and TLR4. NORAD, TLR4 overexpression plasmids and small interfering RNA were transfected into SV40-MES-13 cells respectively. Cell counting kit (CCK-8) assay, 5-ethynyl-2′-deoxyuridine (EdU) assay and flow cytometry were performed to determine the results of cell proliferation and apoptosis. Luciferase activity and their mRNA levels were detected after cotransfection of pGL3-NORAD WT and miR-520h mimics or pGL3-TLR4 WT and miR-520h mimics. After cotransfection of si-NORAD and miR-520h inhibitors, TLR4 overexpression plasmids and miR-520h mimics, and cotransfection of si-TLR4 and miR-520h inhibitors, the levels of NORAD, miR-520h and TLR4, as well as cell proliferation were detected to verify the regulatory relationship among them.

NORAD and TLR4 were upregulated in SV40-MES-13 cells in high glucose group (1.65±0.08 vs 1.00±0.06, P=0.003; 1.96±0.09 vs 1.01±0.07, P=0.001). Overexpression of NORAD and TLR4 promoted the proliferative ability (1.34±0.04 vs 0.85±0.04, P=0.001; 1.33±0.02 vs 0.82±0.03, P<0.001) and inhibited the apoptosis in SV40-MES-13 cells (0.45±0.03 vs 0.94±0.06,P=0.001; 0.51±0.05 vs 0.99±0.03, P=0.001). The dual-luciferase reporter gene assay showed that miR-520h was confirmed to bind to NORAD and TLR4. The expression of NORAD and miR-520h affected each other, and miR-520h mimics reduced the expression of TLR4. The expression of TLR4 in cotransfected NORAD small interference RNA and miR-520h inhibitor was higher than that in NORAD small interference RNA alone (0.74±0.03 vs 0.55±0.03, P=0.014). Cotransfection of miR-520h mimics and TLR4 overexpression plasmids increased cell proliferation compared with miR-520h mimics alone (0.73±0.01 vs 0.61±0.02, P=0.007). Cotransfection of miR-520h inhibitors and TLR4 small interference RNA reduced cell proliferation compared with miR-520h inhibitors alone (1.31±0.04 vs 1.55±0.04, P=0.013).

The regulatory loop NORAD/miR-520h/TLR4 promotes the proliferative ability and inhibits apoptosis in glomerular mesangial cells induced by high glucose.

To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD).

The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire.

A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P<0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation.

The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

Infectious pancreatic necrosis with gastrointestinal fistula is one of the serious complications secondary to severe acute pancreatitis. For patients with infected pancreatic necrosis complicated with duodenal fistula, the author used the relative position relationship between the gastric cavity puncture point and the duodenal fistula to perform intra-lesion irrigation and "postural drainage", which helped to reduce the number of endoscopic debridement and shorten the hospital stay, and achieved success.

Helicobacter pylori infection and its related diseases are important global health problems, and a large number of patients need eradication treatment in clinic. However, with the obvious increase of the resistance rate of commonly used antibiotics, the efficacy of existing eradication programs has decreased significantly, and the situation of eradication treatment has become increasingly severe. It is urgent to develop new programs that are safe, efficient and can be widely used. Recently, the double regimen of proton pump inhibitor and amoxicillin administered 4 times/d has attracted widespread attention from domestic and foreign scholars for its good efficacy, safety and compliance. This article summarizes its history, mechanism of action, research status, advantages and disadvantages, etc., which is beneficial to guide future related research and clinical application.

Diabetic nephropathy (DKD) is one of the serious complications of diabetes and a major cause of end-stage renal insufficiency. The pathogenesis of this disease is complex, and it is generally believed that DKD is the result of the combined action of genetic factors and various environmental factors, but the detailed cellular molecular biological mechanism has not been fully elucidated. Recent studies have found that subcellular organelles and their interactions play an important role in cell biological activities, and mitochondria, endoplasmic reticulum and their tight junctions, namely mitochondria-associated endoplasmic reticulum membrane (MAM) abnormalities play an important role in renal tissue damage in DKD. This paper will briefly introduce the role of mitochondria, endoplasmic reticulum and MAM in the pathogenesis of DKD and its research progress based on the relevant literature at home and abroad and the author's research results.

Currently, there is a lack of effective therapeutic drugs for the treatment of novel coronavirus pneumonia (COVID-19). The convalescent plasma (CP) of COVID-19 recovered patients contains neutralizing antibodies against COVID-19 and has been approved for the treatment of COVID-19 in many countries, but its efficacy still lacks the validation of large-scale randomized controlled trial (RCT) studies. A recent randomized double-blind controlled study confirmed that high-titer convalescent plasma therapy can reduce the risk of developing severe illness in elderly COVID-19 patients.

The inflammatory storm plays an important role in the pathogenesis of severe and critical novel coronavirus pneumonia (hereinafter referred to as COVID-19). Studies confirm that interleukin-6 (IL-6) can be used as a biomarker to warn of inflammatory storms in COVID-19 patients, and that elevated IL-6 levels are associated with poor prognosis in COVID-19. tocilizumab, an IL-6 receptor antagonist, has been used in the treatment of many autoinflammatory diseases such as rheumatoid arthritis. In order to evaluate the efficacy and safety of tocilizumab in the treatment of COVID-19, Mount Sinai Hospital and other hospitals in the United States jointly conducted a global multicenter phase 3 clinical trial. Enrollment criteria were: confirmed cases of COVID-19 hospitalized and aged ≥18 years; Patients who had received either non-invasive positive pressure ventilation or invasive mechanical ventilation were excluded. The study randomized (in a 2:1 ratio) hospitalized patients with COVID-19 who did not receive mechanical ventilation to receive one or two doses of tocilizumab (dose: 8 mg/kg) or placebo, with clinical outcomes including mechanical ventilation and death within 28 days.