[Objective] To use Platelet Additive Solution Ⅲ M to suspend concentrated platelets and evaluate their quality at different storage periods, in order to investigate the optimal ratio of Ⅲ M to plasma in the medium for storing concentrated platelets. [Methods] Disposable plastic blood bags with platelet storage bags were used to collect whole blood from healthy voluntary blood donors, and concentrated platelets were collected by plasma-rich method, with a volume of about 50 mL and ≥4.0×10¹⁰ platelets contained in each bag. According to the Platelet Addictive Solution ⅢM/plasma volume ratio in the medium of suspended platelets, the platelets were divided into 3 groups: control group (plasma only), experimental group 1(Platelet Addictive Solution ⅢM/plasma volume ratio of 6.5∶3.5) and experimental group 2 (low plasma group, Platelet Addictive Solution ⅢM/plasma volume ratio of 9∶1), each group of 50 samples. Three groups of platelets were stored at (22±2) ℃ at a flat-bed shaker, and 5 mL were sampled by sterile connection at day 1, 3, 5 and 7 respectively to detect platelet count, pH value, lactate dehydrogenase, CD62P positive rate and Annexin V positive rate. All the data were analyzed with SPSS24.0 software. One-way ANOVA was employed to compare the differences among three groups. In order to pairwise comparisons between means of multiple samples, Bonferroni method was applied. [Results] With the extension of storage time, the platelet count decreased and the Annexin V positive rate increased in the 3 groups, and the difference of the 3 groups was not statistically significant (P>0.05). The pH value decreased in the 3 groups, with values at day 1, 3, 5 and 7 of 7.44±0.13 vs 7.44±0.14 vs 7.41±0.11, 7.31±0.68 vs 7.43±0.23 vs 7.22±0.12, 7.30±0.15 vs 7.42±0.14 vs 7.17±0.12, 7.29±0.33 vs 7.26±0.18 vs 7.04 ± 0.12, respectively. The pH decline in the control group and experiment group 1 was minor, with no statistically significant difference, but experiment group 2 showed relatively larger decreases in day 5 and day 7, with statistically significant difference (P<0.05). LDH concentrate was elevated in 3 groups (mmol/L), with values at day 1,3,5 and 7 of 169.62±99.33 vs 105.80±150.71 vs 77.14±105.38, 225.10±112.86 vs 116.00±72.77 vs 94.42±88.74, 249.42±79.55 vs 119.00±53.51 vs 118.35±80.39, 253.34±86.95 vs 147.71±90.71 vs 124.68±128.68 respectively. Compared with the control group, the difference was statistically significant (P<0.05). Experimental group1 had the smallest increase; CD62P positive rate increased in 3 groups (%), with values at day 1, 3, 5 and 7 of 26.22±11.74 vs 23.48±12.48 vs 40.49±11.86, 41.29±8.36 vs 33.53±25.64 vs 50.42±22.36, 59.59±10.13 vs 36.39±23.10 vs 50.94±20.50, 72.92±15.44 vs 55.54±23.65 vs 61.89±18.82 respectively. Compared with the control group, the increase in experiment group1 was smaller, and the difference was statistically significant (P<0.05). [Conclusion] Platelet Addictive Solution ⅢM/plasma volume ratio of 6.5∶3.5 is superior to traditional plasma in maintaining platelet quality during the in vitro preservation period of platelets.

Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.

Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P＜0.01,P＜0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

Objective:To detect the level of the circulating cell-free mitochondrial DNA (ccf-mtDNA) in plasma of children with primary carnitine deficiency (PCD)-associated cardiomyopathy and evaluate its clinical significance.Methods:In this prospective case-control study, peripheral blood samples were collected from 7 PCD patients with cardiomyopathy (PCD group), 16 dilated cardiomyopathy (DCM) patients (DCM group), and 50 healthy children (healthy control group) in the Pediatric Cardiovascular Department Ward of First Hospital of Jilin University from July 2017 to June 2022.The ccf-mtDNA levels were measured and compared between groups by the real-time fluorescence quantitative polymerase chain reaction.The correlations between plasma ccf-mtDNA level and blood free carnitine level and cardiac function in the PCD group were analyzed.The changes in the ccf-mtDNA level were monitored after L-carnitine treatment in the PCD group.The Kruskal-Wallis test was used for comparison among the three groups.The Mann-Whitney test was used for comparison between the PCD group and the control group.Changes before and after treatment in the PCD group were analyzed using the paired Wilcoxon rank sum test.The correlation between variables was evaluated by Logistic regression.Results:The plasma ccf-mtDNA levels in the PCD and DCM groups were 3.69×10 6 (1.09×10 6-7.26×10 6) copies/L and 0.99×10 6 (0.25×10 6-4.10×10 6) copies/L, respectively, which were significantly higher than that in the healthy control group[0.09×10 6 (0.01×10 6-0.35×10 6) copies/L]( H=33.34, 24.69; all P<0.01). Besides, the plasma ccf-mtDNA level in the PCD group was higher than that in the DCM group ( H=6.31, P<0.05). In the PCD group, the plasma ccf-mtDNA level was negatively correlated with the blood free carnitine level and left ventricular ejection fraction ( r=-0.85, -0.82, all P<0.05) and positively correlated with the modified Ross score and the N-terminal pro B type natriuretic peptide level ( r=0.81, 0.83, all P<0.05) before L-carnitine treatment.After treatment, the plasma ccf-mtDNA level decreased, and the blood free carnitine level and cardiac function recovered in the PCD group.The plasma ccf-mtDNA level declined sharply from the 3 rd month[0.96×10 6(0.50×10 6-2.27×10 6) copies/L] after treatment ( Z=2.24, P<0.05) and got to 0.27×10 6 (0.18×10 6-0.76×10 6) copies/L, 0.29×10 6(0.19×10 6-0.78×10 6) copies/L, and 0.16×10 6(0.10×10 6-1.06×10 6) copies/L at the 6 th, 9 th, and 12 th months after treatment, respectively, with no statistically significant difference compared to the healthy control group[0.09×10 6(0.01×10 6-0.35×10 6) copies/L] ( Z=1.23, 1.09, 2.12; all P>0.05). Conclusions:Plasma ccf-mtDNA may act as one pathogenic factor of cardiomyopathy in PCD, and monitoring its level is clinically important for heart condition assessment in PCD.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.