Volume 100 ·  Issue 34 ·  2020

Postoperative pain is nociceptive pain that occurs immediately after surgery, and it is also the most common and urgent event in clinic. Poor postoperative analgesia can inhibit immunity, increase the incidence of cardiovascular and cerebrovascular events, prolong the hospital stay, and even further develop into chronic postoperative pain, which affects the prognosis and quality of life of patients^[1]。 With the development of surgery and anesthesia technology, more and more elderly patients are treated by surgery, and a considerable part of them are major surgery, which makes the need for postoperative analgesia in elderly patients stronger than in general patients. However, the particularity of elderly patients increases the difficulty of postoperative analgesia. Common influencing factors include: concomitant diseases and medication, age-related physiological and pharmacological changes, and difficulty in pain assessment.

To analyze the risk factors of postoperative intestinal obstruction (POI) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP).

The clinical data of 573 patients receiving RARP from January to December 2019 in Nanjing Drum Tower Hospital were analyzed retrospectively. According to the occurrence of POI, the cases were divided into the occurrence group and the non-occurrence group. The clinical data of the two groups were compared and the risk factors of POI were investigated by multivariate logistic regression.

Forty-five of 573 patients (7.9%) had POI. Between the two groups, preoperative underlying diseases (cardiopathy, COPD, hypoalbuminemia), preoperative chemotherapy, preoperative WBC, operation time, blood loss, blood transfusion rate, postoperative early fever, length of stay were statistically significant (P<0.05). Multivariable logistic regression analysis showed that heart disease (OR=2.331, P=0.036), COPD (OR=4.285, P=0.001), hypoalbuminemia(OR=2.142, P=0.026), blood loss (≥4.26 ml/kg) (OR=2.388, P=0.010), operative time (≥225 min) (OR=4.200, P<0.001), and postoperative early fever (OR=2.773, P=0.004) were independent risk factors for POI after RARP.

The incidence of POI following RARP is related to multiple perioperative factors. Improving the preoperative heart and lung function, correcting hypoalbuminemia, reducing intraoperative bleeding, shortening the operation time, and preventing early postoperative infection may be important measures to reduce the risk of POI in RARP patients.

To investigate the feasibility and safety of minimally invasive radical prostatectomy for prostate cancer patients without preoperative prostate biopsy in the new era of the continuous development of comprehensive new imaging diagnostic mode and minimally invasive surgery technology.

From August 2018 to October 2019, 17 patients with prostate cancer were enrolled in this study in the Cancer Hospital, Chinese Academy of Medical Sciences. All patients were highly suspected of prostate cancer by PSMA-PET/CT-based imaging diagnostic techniques and underwent 3D laparoscopic radical prostatectomy without prostate biopsy. The perioperative data, postoperative pathology, postoperative complications and follow-up results were recorded and analyzed.

The average age of 17 patients with prostate cancer was (65±7) years. The body mass index (BMI) average was (24.4±3.0) kg/m². The American Society of Anesthesiologists (ASA) score was 1 (1-2) and the Charlson comorbidity index (CCI) score was 1 (0-4). The preoperative value of PSA was (19±11) μg/L. The PSMA PET/CT showed abnormally high expression foci and the great possibility of prostate cancer for all the 17 patients. Prostate puncture biopsy: the results of prostate biopsy were negative in 3 cases. The digital rectal examination found that the prostate volume was Ⅰ or Ⅱ degree large, 10 cases touched hard and the nodule was touched in two cases. Three patients had undergone a previous prostate biopsy, but prostate cancer was not found. All the 17 operations were successfully performed without conversion to open surgery. The surgery time was (85±21) (range from 45 to 120) min, the estimated blood loss was (25±18) (range from5 to 100) ml, the time of intake of liquid diet was (14.3±4.4) h, the intestinal recovery time was (23±10) h, the postoperative activity time was (22±7) h, the drainage duration was (3.7±0.8) d, the postoperative hospital stay was (4.9±1.2) days, and the catheter removal time was (7.4±1.5) days. In the early postoperative period (within 30 days after surgery), no obvious complications occurred. The postoperative final pathology confirmed that all the 17 specimens were prostate cancer. After a median follow-up of 6.5 months, the patient′s urinary control rate reached 81.3% at postoperative 1 month, 92.3% at postoperative 3 months after surgery, and the urinary control rate reached 100% at postoperative 6 months. Postoperative PSA value was (0.08±0.08) μg/L, significantly lower than preoperative PSA level ( P<0.001). There was significant difference between the preoperative and postoperative QOL (Quality of life) score (57±5 and 47±5 respectively,P<0.001) which indicated that the patients′ postoperative quality of life was greatly improved.

It is safe and feasible to perform minimally invasive radical prostatectomy without preoperative prostate biopsy for patients with highly suspected prostate cancer by comprehensive diagnostic mode based on modern new imaging technology.

To explore the correlation between prostate imaging report and data system (PI-RADS) score and international society of uological pathology (ISUP) grade of prostate cancer (PCa) and the role of PI-RADS score in predicting the pathological features of clinically significant PCa (csPCa), positive surgical margin and pathological upgrade.

The pathologically positive patients with multi-parameter magnetic resonance image (mpMRI) were included in this study. The patients with prostate specific antigen (PSA)<100 μg/L were divided into two groups: biopsy group (n=523) and RP group (n=215). The correlation between PI-RADS score and ISUP grade and the accuracy of predicting csPCa in the two groups were evaluated. In the RP group, the correlation between PI-RADS score and postoperative pathological grade or degradation and positive incisal margin was further discussed. The patients with PSA≥100 μg/L (171cases in biopsy group and 6 cases in RP group) were not included in the statistical analysis, and the results were simply described.

The age, prostate volume, and PSA level of biopsy group and RP group was (72±8) years vs (68±7) years, 48.3 (32-57) cm³ vs 47.2 (32-54) cm³, and 26.3(10.2-34.2)μg/L vs 21.7 (9.24-23.95)μg/L, respectively. The PI-RADS scores ≤ 3,4, and 5 in the biopsy group were 109,97, and 317 respectively, and those in the RP group were 61,55, and 99 respectively. There were significant differences in the composition of ISUP grades of different PI-RADS scores between the two groups (P<0.001), and there was a positive correlation between the two groups (r=0.493 in the biopsy group, r=0.671 in the RP group, both P<0.001). Using PI-RADS score to predict csPCa, biopsy group (AUC=0.764, P<0.001, 95%CI:0.710-0.819) and RP group (AUC=0.807, P<0.001, 95%CI:0.735-0.879) had certain accuracy. The PI-RADS score combined with PSA could improve the accuracy of csPCa prediction in the biopsy group (AUC=0.795,P<0.001, 95% CI:0.746-0.843) and the RP group (AUC=0.852, P<0.001, 95%CI:0.789-0.915). Compared with the pathological results of biopsy in the RP group, 52.6% of the patients showed upgrade and degrade of ISUP, and there was insignificant difference in the composition of PI-RADS scores between upgraded and degraded patients (P>0.05). However, 41.7%(27/65) of the patients with ISUP grade 1 biopsies had pathological upgrades that the patients with PI-RADS ≤ 3 accounted for 33.3%, while the patients with PI-RADS>3 accounted for 66.7%, and there was significant difference between the two groups (P<0.05). After RP, 43.3% of the patients had positive surgical margins, and the patients with PI-RADS score ≤ 3, 4 and 5 were 13 (14%), 24 (25.8%) and 56 (60.2%), respectively, while the PI-RADS scores of patients with negative surgical margin were 48 (39.3%), 31(25.4%) and 43(35.2%), respectively. There was significant difference between the two groups (P<0.001). The higher the PI-RADS score, the greater the possibility of the positive surgical margin. For the patients with PSA ≥ 100 μg/L, 98.8% (169/171) patients in the biopsy group had a PI-RADS score 5. The pathological results of all patients were csPCa, of which 85.4% (146/171) had ISUP grade ≥ 4. Among them, 6 cases underwent RP, 5 cases had ISUP grade ≥ 4, all surgical margin were positive, 5 cases had seminal vesicle invasion, 3 cases had capsule invasion and 3 cases had positive pelvic lymph nodes.

ThePI-RADS score is correlated with the ISUP grade of PCa. Combined with PSA can accurately predict csPCa. At the same time, the higher PI-RADS score, the more likely the patients with positive incisal margin after RP and Gleason score of 3+3=6 at the time of puncture will be upgraded pathologically.

To investigate Notch receptor expression in CD8⁺ T cells in patients with prostate cancer, and to assess the influence of Notch signaling pathway on the function of CD8⁺T cells inpatients with prostate cancer.

Forty-five patients with prostate cancer, forty-one patients with nonbacterial prostatitis, and thirty healthy controls who were hospitalized or followed-up in Shanxi Provincial People′s Hospital between November 2017 and June 2018 were enrolled. CD8⁺T cells were purified, and mRNA relative levels of Notch1-4 were semi-quantified by reverse transcriptional real-time PCR. CD8⁺T cells were stimulated with Notch signaling inhibitor γ-secretase inhibitor (GSI). mRNA relative levels of perforin, granzyme B, and FasL were semi-quantified by reverse transcriptional real-time PCR. Percentages of PD-1 and CTLA-4 positive cells were investigated by flow cytometry. Direct contact and indirect contact coculture systems were set up between CD8 ⁺T cells and prostate cancer cell line LAPC4 cells. The influence of Notch signaling inhibition to CD8⁺T cell cytotoxicitywas assessed by measuringtarget cell death and cytokine secretion. One-Way ANOVA, LSD-t test, and paired t test was used for comparison.

mRNA relative levels of Notch1~4 were elevated in CD8⁺T cells from prostate cancer patients when compared with those from healthy controls and nonbacterial prostatitis patients (all P<0.05). There was CD8⁺T cell exhaustion in prostate cancer patients, which presented as decreased mRNA relative levels of perforin, granzyme B, and FasL (all P<0.000 1), as well as increased percentage of PD-1⁺CD8⁺ (19.3%±5.4%) and CTLA-4⁺CD8⁺(11.7%±3.9%) cells. CD8⁺T cells from prostate cancer patients induced LAPC cell death was downregulated in direct contact coculture system (28.8%±6.4% vs 37.2%±2.6%, P=0.015). IFN-γsecretion was also reduced ((61.7±10.6)ng/L vs (88.6±20.2)ng/L,P=0.003 2). Inhibition of Notch signaling by GSI increased mRNA of perforin, granzyme B, and FasL in CD8⁺T cells from prostate cancer patients (all P<0.01), while reduced percentage of PD-1⁺CD8⁺(12.6%±2.5% vs 17.4%±4.7%, P=0.005 9) and CTLA-4⁺CD8⁺ (12.0%±1.0% vs 14.1%±3.1%, P=0.011)cells. Notch signaling inhibition promoted LAPC4 cell death (34.3%±7.2%, P=0.000 2) which induced by prostate cancer derived CD8⁺T cells, and increased IFN-γ production ((88.4±33.6)ng/L,P=0.008 3).

Elevated Notch receptors induced CD8⁺T cells exhaustion in prostate cancer patients.

To explore the relationship between insomnia phenotype and mild cognitive impairment (MCI) in young and middle-aged patients with obstructive sleep apnea hypopnea syndrome (OSAHS).

Those patients admitted due to snoring and examined by polysomnography (PSG) in the Sleep Center of the Second Affiliated Hospital of Soochow University from January 2014 to January 2019 were screened. They were between 30 and 60 years old, and their cognitive function was assessed by the Montreal cognitive assessment (MoCA) and their sleep quality was assessed by the Pittsburgh sleep quality index (PSQI). According to the sleep apnea hypopnea index (AHI), the patients were divided into three groups: snoring group (AHI<5 times/h), mild/moderate OSAHS group (5≤AHI≤30 times/h) and severe OSAHS group (AHI>30 times/h). According to the results of PSQI score, the patients were further divided into non-insomnia group (PSQI total score<8) and insomnia group (PSQI total score≥8). The differences of parameters in different groups were compared, and the relationship between OSAHS insomnia phenotype and MCI was analyzed by binary logistic regression model.

A total of 2 098 patients with the average age of (42.7±8.4) years old and the average BMI of (26.3±3.6) kg/m² were enrolled in the study, including 398 cases in snoring group (including 254 cases in non-insomnia group and 144 cases in insomnia group), 754 cases in mild/moderate OSAHS group (including 446 cases in non-insomnia group and 308 cases in insomnia group) and 946 cases in severe OSAHS group (including 722 cases in non-insomnia group and 224 cases in insomnia group). In the mild/moderate OSAHS group, compared with the non-insomnia group, the proportion of women in the insomnia group was higher with lighter degree of obesity, lighter severity of illness and lighter degree of hypoxia (all P<0.05). In the severe OSAHS group, the general characteristics of insomnia patients were similar to those of the mild/moderate OSAHS group, and the MoCA score of the insomnia group was lower than that of the non-insomnia group [(26.3±2.7) vs (25.5±2.9) points] (P=0.001). In the evaluation of each item of PSQI, the total score and daytime dysfunction score of insomnia patients in mild/moderate OSAHS group and severe OSAHS group was higher than those in snoring group [(11.2±1.9) points, (12.8±2.2) points vs (10.9±2.1) points and (1.5±0.4) points, (1.9±0.8) points vs (0.5±0.5) points], but the score in sleep latency was lower than that in snoring group [(1.5±0.5) points, (1.5±0.5) points vs (2.1±0.8) points] (allP<0.05). After correcting the effects of OSAHS disease severity, hypoxia, awake times, education, age, gender, hypnagogue, BMI, smoking and drinking history, the risk of MCI in insomnia group of severe OSAHS patients was significantly higher than that of non-insomnia group by 49% (OR=1.49, 95%CI: 1.05-2.11).

Insomnia phenotype is a common clinical phenotype of OSAHS, and it is a risk factor for MCI in young and middle-aged patients with severe OSAHS.

The aim of present study was to investigate the influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy.

This study was designed as a retrospective analysis, and a total of 278 patients with postoperative NSCLC who received platinum-based adjuvant chemotherapy from January 2012 to December 2018 in the Department of Respiratory Medicine of the First affiliated Hospital of Zhengzhou University were included in this study. Biological specimens of the patients were collected during hospitalization. Recurrence status and adverse reactions were evaluated in the hospital during adjuvant chemotherapy. Survival data of the patients were obtained through telephone follow-up after completing the fixed cycle of adjuvant chemotherapy. DNA extracted from the collected hematological specimens was genotyped for PD-L1 gene polymorphism. Additionally, postoperative cancer tissue specimens from 68 patients were collected for RNA extraction in order to perform the PD-L1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis.

Prognostic results indicated that the median disease-free survival (DFS) of the 278 patients with NSCLC was 3.2 years and the median overall survival (OS) was 4.9 years. The prevalence of -1813G>C polymorphism were: GG genotype 173 cases (62.23%), GC genotype 92 cases (33.09%), CC genotype 13 cases (4.68%), the minor allele frequency was 0.21, the distribution of the three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.864). In view of the rare frequency of CC genotype, GC and CC genotype were merged in the following analysis. The survival analysis results of the two genotype groups suggested that the median DFS of patients with GG and GC/CC genotype was 2.7 and 4.0 years, which was statistically significant (P=0.013). Furthermore, the median OS of patients with GG and GC/CC was 4.0 and 5.4 years respectively, which was statistically significant as well (P=0.009). However, the safety analysis failed to find the significant association between the polymorphism and adverse events (P>0.05). Interestingly, expression analysis of RNA extracted from cancer tissues specimens indicated that the PD-L1 mRNA expression of the patients with GG genotype were significantly higher than those of the GC/CC genotype (3.67±0.65 vs 2.69±0.78, P<0.001).

The prognosis of patients with postoperative non-small cell lung cancer who received platinum-based adjuvant chemotherapy is influenced by -1813G>C polymorphism of PD-L1 gene.

To investigate the effects and potential mechanisms of Helicobacter pylori (H.pylori) infection on azoxymethane (AOM)/dextran sulfate sulphate (DSS) induced colitis-associated cancer (CAC) in mice.

A total of 60 specific pathogen free C57BL/6J mice were randomly divided into four groups: normal control group (control group, n=9), H. pylori-infected group (Hp group, n=9), AOM/DSS-treated group (AOM/DSS group,n=21) and AOM/DSS-treated with H.pylori infection group (Hp+AOM/DSS group, n=21). Mice were sacrificed on day19, 45 or 85 after AOM/DSS challenge. Histopathological changes in colonic tissues were determined by hematoxylin and eosin staining. Flow cytometry analysis was performed to determine T helper cells 17 (Th17) and regulatory T cells (Treg) in colonic lamina propria. The expression levels of Th17-and Treg-associated cytokines and transcription factors [interleukin (IL)-10, IL-17A, retinoic acid receptor-related orphan receptor γt (RORγt) and forkhead box P3 (Foxp3)] were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.

There were no histopathological changes in colonic tissues of mice in control group and Hp group. H.pylori colonization reduced the histopathological scores at the stages of colitis (day 19) and dysplasia (day 45), and also decreased tumor load (day 85) in mice treated with AOM/DSS (all P<0.05). Compared with AOM/DSS group, the percentages of CD3⁺CD4⁺IL-17A⁺Th17 and CD3⁺CD4⁺IL-17A⁺Foxp3⁺Treg cells (1.88±0.17 vs 2.07±0.89, 1.06±0.13 vs 1.89±0.23) and the expression levels of RORγt and IL-17A (1.08±0.59 vs 2.35±1.35, 2.96±0.92 vs 7.78±4.57) were decreased in colonic tissues of Hp+AOM/DSS group (allP<0.05). The percentages of CD3⁺CD4⁺CD25⁺Foxp3⁺Treg and CD3⁺CD4⁺IL-10⁺Foxp3⁺Treg cells (20.60±3.39 vs 15.63±2.71, 2.94±0.52 vs 2.14±0.47) and the expression levels of Foxp3 and IL-10 [17.59(13.77,24.87) vs 6.27(4.41,13.36), 3.52(1.59,5.99) vs 1.17(1.15,2.75)] in colonic tissues were higher (all P<0.05) in mice of Hp+AOM/DSS group compared with AOM/DSS group on day 85.

H.pylori infection slows the progress from inflammation to tumor in a AOM/DSS induced CAC modal, accompanied with the downregulation of Th17 response and upregulation of Treg response.

To analyze the epidemic characteristics of hand, foot and mouth disease (HFMD) in Beijing and explore the short-term lag effect of daily average temperature on HFMD.

The incidence data and meteorological data of HFMD were collected from Xicheng District, Chaoyang District, and Changping District of Beijing between January 2009 and December 2018. The dose-response relationship and short-term lag effect of temperature and HFMD incidence were explored by the distributed lag non-linear model (DNLM).

From 2009 to 2018, a total of 97 210 cases of HFMD were confirmed in Xicheng District, Chaoyang District, and Changping District of Beijing. The incidence rate of HFMD in Xicheng district was 71.83/100 000, which was the lowest in three districts. The total annual average incidence was 146.89/100 000 in the three districts. The cases were concentrated from May to July, with a small peak in October to November. The ratio of male to female was 1.49∶1, and the median age of the patients was 3.08 (1.89, 4.39) years old, which showed a decreasing trend in children under 6 years old (Z=-30.11, P<0.01). The DNLM showed that the cumulative relative risk (RR) curve had a bimodal distribution, with RR of 1.36 (95%CI: 1.05-1.76) and 1.35 (95%CI: 1.10-1.66), and the peak values appeared at 4 ℃ and 26 ℃, respectively.

The incidence rate of HFMD in Xicheng was the lowest in three districts of Beijing. In addition, the incidence of HFMD is seasonal, and the incidence is higher in spring and summer than that in autumn and winter. Daily average temperature had a lag effect on HFMD, which was different between high temperature and low temperature.

Precise dose control is very important for drug-based therapy. It is well known that the regulation of blood glucose levels is a closed-loop homeostasis process. The mechanisms by which glucose stimulates insulin release from pancreatic islet beta cells include glucose absorption and metabolism, adenosine triphosphate-mediated potassium channel closure, plasma membrane depolarization, and voltage-gated calcium channel opening, leading to intracellular Ca²⁺The concentration surges while causing the rapid release of insulin from the storage vesicles. In order to accurately control the amount of insulin secreted, intervening in this process requires the use of an electrical interface that can directly program cell behavior through digital electronic input. The authors propose a cofactor-free bioelectronic interface that directly correlates radio stimulation of human cells with synthetic promoter-driven transgene expression and also with rapid secretion of constitutively expressed protein therapeutics stored in vesicles. Electrogenetic control through the L-type voltage-gated channel Ca_v1.2 and inward rectifying potassium channel K_ir2.1 Coupled ectopic expression is achieved, achieving the desired output through endogenous calcium signaling. Focusing on type 1 diabetes, the authors designed electrosensitive human beta cells (_Electrobeta cells)._ElectroBeta cells have customized bioelectronic devices inside, and radio stimulation of them can control the release of insulin in the vesicles in real time, and insulin levels can reach a peak within 10 min. Subcutaneous implantation in type 1 diabetic mice_ElectroBeta cells, an electrogenetically controlled vesicle release system that normalizes blood sugar in mice. Today, with the increasing number of patients with chronic diseases such as diabetes, precise control of drug dosage is the key to the success of drug therapy. This way of accurately controlling drug dosage through direct communication between devices and implanted cells is expected to customize individualized precision for patients. Medical care provides new exploration directions.

Understanding the health effects of heatwaves is particularly important due to the enormous burden of disease caused by heatwaves and the increased frequency and intensity of heatwaves due to climate change. Recently, researchers from the Chinese Center for Disease Control and Prevention (CDC) explored the risk of death due to the nature of heatwaves, including the season, the duration, intensity and duration of heatwaves, and the effects of changes in temperature regions.

The use of potassium chloride in substitute salt to replace part of sodium chloride in table salt may reduce the risk of hypertension. The researchers designed a ladder-wedge group randomized trial to conduct a population epidemiological study in six villages in Peru, aiming to explore the implementation and effect of salt reduction strategies by substitute salt in the population. In the families participating in the study, conventional table salt was recovered and replaced, and substitute salt containing 25% potassium chloride +75% sodium chloride was used free of charge to replace ordinary table salt. The hypotensive effect of substitute salt was evaluated by measuring 24-h urinary sodium excretion and blood pressure. A total of 2 376 Peruvian villagers participated in the study. After 4 months of intervention, analysis of intention (ITT) results showed that participants' systolic and diastolic blood pressure decreased by an average of 1.29 mmHg (95%CI: -2.17~ -0.41 mmHg) and 0.76 mmHg (95%CI: -1.39 to-0.13 mmHg). Villagers with hypertension or over 60 years old have the most obvious effect of changing salt to lower blood pressure. After excluding more than 400 hypertensive patients, those who used substitute salt had a 51% (95%) lower risk of hypertension compared with controlsCI：29%~66%）。 In 24 h urine samples, there was no evidence of change in sodium levels from baseline, with a mean difference of 0.01 g (95%CI: -0.23-0.25 g); However, at the end of the study, potassium levels were higher than baseline, with a mean difference of 0.63 g (95%CI: 0.47-0.78 g). The findings confirm the effectiveness and feasibility of the alternative salt strategy, supporting the implementation of a pragmatic, population-wide salt replacement strategy to reduce blood pressure and hypertension incidence.