Objective:To explore the influence of LIN28B on chemosensitivity of colon cancer by regulating GSH.Methods:Functional enrichment analysis of LIN28B target genes was performed using database. The primary tumor tissues of colon cancer patients who received neoadjuvant chemotherapy at Department of Gastroenterology, Peking University International Hospital from Nov 2017 to May 2020 were collected, and their LIN28B levels were detected by immunohistochemistry. According to the tumor regression grade, they were divided into chemotherapy sensitive group and chemotherapy resistant group, and the difference of LIN28B expression between the two groups was compared. LIN28B overexpression and knockdown colon cancer cell lines were constructed, and the effect of LIN28B on the chemosensitivity of colon cancer cells was detected by MTT assay. Double luciferase reporting experiment and Western blot were used to detect the direct binding and regulation of LIN28B to mRNA of four GSH related enzymes. At the same time, the regulation of LIN28B on total GSH and reduced GSH was tested. Finally, by detecting the level of reactive oxygen species (ROS) γ-H2AX and Comet assay to analyze the potential impact of LIN28B on genomic instability.Results:GSH-related enzymes were highly enriched in LIN28B target genes. The expression of LIN28B was heterogeneous in colon cancer patients. Compared with the low expression group, the average survival time of patients with high expression of LIN28B was significantly increased [(50.2±2.9 )months vs. (31.1±4.0 )months, P=0.001], and the proportion of tumor regression grade 0-1 was significantly different (48.0% vs. 16.0%, P=0.032). The expression level of LIN28B in chemotherapy sensitive group was significantly higher than that in drug resistant group ( P<0.01). LIN28B overexpression significantly increased the chemosensitivity of HCT116 cells to 5-fluorouracil (5-Fu) and oxaliplatin (L-OPH). The synthesis and activity of GSH were further inhibited (all P<0.01). At the same time, the ROS level of LIN28B overexpression cells was significantly increased after treatment with L-OPH. The level of γ-H2AX was significantly increased, and the content of comet tail DNA was also significantly increased ( P<0.01). Conclusion:LIN28B may increase the chemosensitivity of colon cancer cells by directly inhibiting the expression of GSH related enzymes, resulting in the decrease of GSH synthesis and activity, the increase of ROS level and genomic instability.

OBJECTIVE:Researches show that a combination of platelet-rich plasma and adipose-derived stem cells can accelerate the healing of skin lesions.However,systematic evidence for the combination of the two is still lacking.The purpose of this study was to assess the efficacy of a combination of two interventions in a clinical rodent skin wound model.METHODS:We searched PubMed,Embase,Cochrane,and CNKI and selected the studies of platelet-rich plasma,adipose-derived stem cell transplantation,or their combination on skin wounds in experimental animals published until July 2023.Wound healing and wound transformation growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor were used as indicators.RevMan 5.3 and Stata 15.0 were used to analyze the data.RESULTS:A total of 12 studies were included,of which 8 studies used rats as experimental subjects and 4 studies used mice as experimental subjects.The experimental group was treated with platelet-rich plasma combined with adipose-stem cell transplantation,and the control group was treated with platelet-rich plasma alone.The results of meta-analysis showed that the wound healing rate of the experimental group at 3,7,and 10 days after treatment was greater than that of the control group[SMD=2.65,95％CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95％CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95％CI(1.50,3.73),Z=4.61,P<0.00001].The wound healing time of the experimental group was shorter than that of the control group[SMD=-2.12,95％CI(-3.5,-0.74),P=0.003].The expression of transforming growth factor β,positive rate of CD31,expression of type Ⅰ collagen,and vascular endothelial growth factor in wound of experimental group were higher than those of control group[SMD=5.65,95％CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95％CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95％CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95％CI(0.97,3.79),Z=3.30,P=0.0010].CONCLUSION:Our results show that platelet-rich plasma+adipose-derived stem cells combined treatment can improve the wound healing rate,shorten the wound healing time,and at the same time increase the expression of transforming growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor to accelerate healing.Due to the limitations of the model,more animal testing and clinical trials are needed.

Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides ²³⁸U, ²³²Th, and ²²⁶Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.

OBJECTIVE:Researches show that a combination of platelet-rich plasma and adipose-derived stem cells can accelerate the healing of skin lesions.However,systematic evidence for the combination of the two is still lacking.The purpose of this study was to assess the efficacy of a combination of two interventions in a clinical rodent skin wound model.METHODS:We searched PubMed,Embase,Cochrane,and CNKI and selected the studies of platelet-rich plasma,adipose-derived stem cell transplantation,or their combination on skin wounds in experimental animals published until July 2023.Wound healing and wound transformation growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor were used as indicators.RevMan 5.3 and Stata 15.0 were used to analyze the data.RESULTS:A total of 12 studies were included,of which 8 studies used rats as experimental subjects and 4 studies used mice as experimental subjects.The experimental group was treated with platelet-rich plasma combined with adipose-stem cell transplantation,and the control group was treated with platelet-rich plasma alone.The results of meta-analysis showed that the wound healing rate of the experimental group at 3,7,and 10 days after treatment was greater than that of the control group[SMD=2.65,95％CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95％CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95％CI(1.50,3.73),Z=4.61,P<0.00001].The wound healing time of the experimental group was shorter than that of the control group[SMD=-2.12,95％CI(-3.5,-0.74),P=0.003].The expression of transforming growth factor β,positive rate of CD31,expression of type Ⅰ collagen,and vascular endothelial growth factor in wound of experimental group were higher than those of control group[SMD=5.65,95％CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95％CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95％CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95％CI(0.97,3.79),Z=3.30,P=0.0010].CONCLUSION:Our results show that platelet-rich plasma+adipose-derived stem cells combined treatment can improve the wound healing rate,shorten the wound healing time,and at the same time increase the expression of transforming growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor to accelerate healing.Due to the limitations of the model,more animal testing and clinical trials are needed.

Objective:To explore the influence of LIN28B on chemosensitivity of colon cancer by regulating GSH.Methods:Functional enrichment analysis of LIN28B target genes was performed using database. The primary tumor tissues of colon cancer patients who received neoadjuvant chemotherapy at Department of Gastroenterology, Peking University International Hospital from Nov 2017 to May 2020 were collected, and their LIN28B levels were detected by immunohistochemistry. According to the tumor regression grade, they were divided into chemotherapy sensitive group and chemotherapy resistant group, and the difference of LIN28B expression between the two groups was compared. LIN28B overexpression and knockdown colon cancer cell lines were constructed, and the effect of LIN28B on the chemosensitivity of colon cancer cells was detected by MTT assay. Double luciferase reporting experiment and Western blot were used to detect the direct binding and regulation of LIN28B to mRNA of four GSH related enzymes. At the same time, the regulation of LIN28B on total GSH and reduced GSH was tested. Finally, by detecting the level of reactive oxygen species (ROS) γ-H2AX and Comet assay to analyze the potential impact of LIN28B on genomic instability.Results:GSH-related enzymes were highly enriched in LIN28B target genes. The expression of LIN28B was heterogeneous in colon cancer patients. Compared with the low expression group, the average survival time of patients with high expression of LIN28B was significantly increased [(50.2±2.9 )months vs. (31.1±4.0 )months, P=0.001], and the proportion of tumor regression grade 0-1 was significantly different (48.0% vs. 16.0%, P=0.032). The expression level of LIN28B in chemotherapy sensitive group was significantly higher than that in drug resistant group ( P<0.01). LIN28B overexpression significantly increased the chemosensitivity of HCT116 cells to 5-fluorouracil (5-Fu) and oxaliplatin (L-OPH). The synthesis and activity of GSH were further inhibited (all P<0.01). At the same time, the ROS level of LIN28B overexpression cells was significantly increased after treatment with L-OPH. The level of γ-H2AX was significantly increased, and the content of comet tail DNA was also significantly increased ( P<0.01). Conclusion:LIN28B may increase the chemosensitivity of colon cancer cells by directly inhibiting the expression of GSH related enzymes, resulting in the decrease of GSH synthesis and activity, the increase of ROS level and genomic instability.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective To evaluate the clinical application of automatic coagulation detection assembly line in high-throughput specimen detection.Methods The relevant information of sodium citrate anticoagulation samples in Zhongshan Hospital Affiliated to Fudan University from June to August 2021 was collected,inclu-ding sample collection time,receiving time,instrument sucking time,test completion time,and whether it pas-sed autoverification or not.The sample pretreatment time,testing time and turnaround time(TAT)of the au-tomatic coagulation detection assembly line were compared before and after installation,and the detection speed of the automatic coagulation detection assembly line was evaluated.Results The automatic coagulation detection line was expected to detect 650-900 samples per hour.The increase in the number of turbidimetric tests would slow down the detection speed of the instrument.Automatic coagulation detection assembly line test specimen to clinic and ward of pretreatment time and testing time were shorter than single detection,the differences were statistically significant(P＜0.05).The automatic coagulation detection assembly line could shorten TAT(P＜0.05).After the application of automatic coagulation detection assembly line,the autoveri-fication rate was 25.6％.Conclusion The automatic coagulation detection assembly line is suitable for high-throughput specimen detection in laboratory.Compared with stand-alone coagulation detection,the automatic coagulation detection assembly line could shorten TAT and testing time,and help to reduce the work pressure of laboratory personnel.

Objective:To analyze the effect of perineural invasion(PNI)on immune cell infiltration in pancreatic ductal adenocarcinoma(PDAC)by the CIBERSORT deconvolution algorithm.Methods:The pancreatic cancer patients from the dataset GSE102238 were re-evaluated for the severity of PNI.And then the high and low PNI subgroups were subjected to immune scoring and immune cell infiltration analysis using the ESTIMATE and CIBERSORT algorithms to find immune cell subgroups associated with PNI.Finally,the results were validated by tissue microarrays.Results:Twenty-five cases were selected from 50 pancreatic cancer specimens for PNI reassessment and then divided into two high and low groups.Compared to the low PNI group,specimens from patients in the high group showed significantly less CD8+T-cell infiltration(P<0.05)and significantly more resting memory CD4+T-cells and M0 macrophages(P<0.05).Significantly reduced CD8+T cells(P<0.01)and slightly increased CD4+T cells(P<0.05)were confirmed in the patients with the high PNI using tissue microarrays.Meanwhile,macrophages significantly increased in the high PNI group(P<0.001).Conclusion:High PNI in PDAC inhibits infiltration of CD8+T cells which promote the infiltration of macrophages.

Objective:To analyze the effect of perineural invasion(PNI)on immune cell infiltration in pancreatic ductal adenocarcinoma(PDAC)by the CIBERSORT deconvolution algorithm.Methods:The pancreatic cancer patients from the dataset GSE102238 were re-evaluated for the severity of PNI.And then the high and low PNI subgroups were subjected to immune scoring and immune cell infiltration analysis using the ESTIMATE and CIBERSORT algorithms to find immune cell subgroups associated with PNI.Finally,the results were validated by tissue microarrays.Results:Twenty-five cases were selected from 50 pancreatic cancer specimens for PNI reassessment and then divided into two high and low groups.Compared to the low PNI group,specimens from patients in the high group showed significantly less CD8+T-cell infiltration(P<0.05)and significantly more resting memory CD4+T-cells and M0 macrophages(P<0.05).Significantly reduced CD8+T cells(P<0.01)and slightly increased CD4+T cells(P<0.05)were confirmed in the patients with the high PNI using tissue microarrays.Meanwhile,macrophages significantly increased in the high PNI group(P<0.001).Conclusion:High PNI in PDAC inhibits infiltration of CD8+T cells which promote the infiltration of macrophages.

Objective: To evaluate the effectiveness of craniocervical flexion training using pressure biofeedback combined with cervical traction among patients with cervical spondylotic radiculopathy (CSR). Methods: Sixty patients with CSR receiving treatment in Center of Rehabilitation, Zhejiang Hospital from January 2020 to December 2021 were enrolled and randomly assigned into the control and treatment groups, of 30 patients in each group. All patients were given cervical traction, and patients in the treatment group were given additional craniocervical flexion training using pressure biofeedback for successive four weeks. The effectiveness of craniocervical flexion training combined with cervical traction was evaluated using Visual Analogue Scale (VAS), Neck Disability Index (NDI) and the active range of motion (AROM) of cervical flexion, and the neck pain and cervical functions were compared between the two groups before and after treatments using repeated-measures analysis of variance. Results: Fifteen men were included in the treatment group, with a mean age of (49.47±5.33) years, mean disease course of (5.53±2.89) months, and mean VAS score of (4.73±1.39) points, and there were no significant differences between the control and treatment groups in terms of gender, age, course of disease or VAS score (P>0.05). The VAS score and NDI were lower 4 weeks post-treatment than pretreatment in both the treatment [VAS score: (2.13±1.01) vs. (4.73±1.39); NDI: (12.17±2.12) vs. (20.20±3.78)] and control groups [VAS score: (2.93±1.11) vs. (4.90±1.21); NDI: (15.23±2.39) vs. (19.60±3.30)], and the AROM of cervical flexion was significantly higher 4 weeks post-treatment than pretreatment in both the treatment [(42.87°±2.99°) vs. (37.50°±2.80°)] and control groups [(41.80°±3.61°) vs. (38.07°±2.99°)]; there was an interaction between time and group, and a higher improvement for cervical functions was seen in the treatment group than in the control group (FVAS =5.119, P=0.027; FNDI=15.473, P<0.001; FAROM=11.443, P<0.001). Conclusion Craniocervical flexion training using pressure biofeedback combined with cervical traction may effectively alleviate the neck pain and increase the AROM among patients with CRS, which is more effective to improve patients' cervical functions than cervical traction alone.