Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To investigate the clinical and diffusion imaging of brain damage in patients with neurosyphilis.Methods Eighty patients with neurosyphilis with brain damage were retrospectively selected as the study group,and were divided into mild group(n=38)and moderate to severe group(n=42)according to imaging results.Another 80 healthy subjects in the same period were selected as the control group.The values of apparent diffusion coefficient(ADC)and fractional anisotropy(FA)were compared among the three groups.Pearson test was used to analyze the correlation between ADC and FA values in various brain regions and cognitive function in patients with neurosyphilis brain damage.Results ADC values in parieto-occipital lobe,frontal lobe,basal gan-glia and hemioval center in moderate to severe group were significantly higher than those in mild group and control group,and FA values were significantly lower than those in mild group and control group(P<0.05).The results of Pearson analysis showed that the ADC and FA values of parieto-occipital lobe,frontal lobe and hemioval center were significantly correlated with Wechsler adult intel-ligence scale-revised of China(WAIS-RC)knowledge,WAIS-RC arithmetic,verbal fluency test(VFT),Montreal cognitive assess-ment(MoCA),forward digit span test(FDST),trail making test A(TMT-A)and trail making test B(TMT-B)scores(P<0.05).Conclusion The ADC and FA values of parieto-occipital lobe,frontal lobe,basal ganglia and hemioval center are closely related to the severity of brain damage,which is helpful for clinical diagnosis.

With the development of technology,humans are increasingly exposed to radio frequency electromagnetic fields.Previous studies have shown that radio frequency radiation could affect public health,but there was no consensus on whether radio frequency radiation affected human cognitive function,and most experimental results were not reproducible.Based on literature currently available,this paper reviews the measurement and control methods of public exposure and laboratory exposure to radio frequency electromagnetic fields,and the effects of long term and short term electromagnetic radiation on cognitive function and neural activity of the human brain.The existing problems are summarized,prospects are predicted,and recommendations are given as to how the influence of radio frequency electromagnetic fields on cognitive function should be studied in the future.

Objective To investigate the clinical and diffusion imaging of brain damage in patients with neurosyphilis.Methods Eighty patients with neurosyphilis with brain damage were retrospectively selected as the study group,and were divided into mild group(n=38)and moderate to severe group(n=42)according to imaging results.Another 80 healthy subjects in the same period were selected as the control group.The values of apparent diffusion coefficient(ADC)and fractional anisotropy(FA)were compared among the three groups.Pearson test was used to analyze the correlation between ADC and FA values in various brain regions and cognitive function in patients with neurosyphilis brain damage.Results ADC values in parieto-occipital lobe,frontal lobe,basal gan-glia and hemioval center in moderate to severe group were significantly higher than those in mild group and control group,and FA values were significantly lower than those in mild group and control group(P<0.05).The results of Pearson analysis showed that the ADC and FA values of parieto-occipital lobe,frontal lobe and hemioval center were significantly correlated with Wechsler adult intel-ligence scale-revised of China(WAIS-RC)knowledge,WAIS-RC arithmetic,verbal fluency test(VFT),Montreal cognitive assess-ment(MoCA),forward digit span test(FDST),trail making test A(TMT-A)and trail making test B(TMT-B)scores(P<0.05).Conclusion The ADC and FA values of parieto-occipital lobe,frontal lobe,basal ganglia and hemioval center are closely related to the severity of brain damage,which is helpful for clinical diagnosis.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To develop an Exercise Behavior Perception Scale for Lung Cancer Patients in China,and to test its reliability and validity.Methods According to the health belief model,the first draft of the scale was formed through literature review,semi-structured interview,research group discussion,2 rounds of expert correspondence and pre-survey.A total of 842 patients with lung cancer who received treatment in a tertiary A hospital in Zhengzhou City from October 2022 to April 2023 were selected for investigation,and item analysis,validity analysis,and reliability analysis were applied to adjust the items to form a formal scale.Results The Exercise Behavior Perception Scale for Lung Cancer Patients contained 24 items,and exploratory factor analysis generated 6 common factors,including physical rehabilitation benefits,emotional and mental benefits,information disorders,disease symptom disorders,condition disorders,and psychological disorders.The cumulative variance contribution rate reached 73.916％,and the results of confirmatory factor analysis showed that the model fit was good,the x2/df was 2.371,the root mean square error of approximation was 0.057,the normed fit index was 0.924,and the comparative fit index was 0.954,the scale score was moderately positively correlated with the total score of the Frenchay activities index(r=0.529,P＜0.001).The Cronbach's α,coefficient,half reliability,and retest reliability of the scale were 0.884,0.741,and 0.889,respectively.Conclusion The Exercise Behavior Perception Scale for Lung Cancer Patients had good reliability and validity,and it can be used to effectively evaluate the exercise behavior perception status of lung cancer patients.

Objective To study the differences and mechanisms of damage to the reproductive organs of male rats by single and compound exposure to microwaves at 2.856 and 9.375 GHz.Methods A total of 40 male Wistar rats were randomly divided into sham group,S10 group,X10 group and SX5 group.Microwavesat 2.856 and 9.375 GHz were used to expose the rats for 6 min in the S10 and X10 groups with an average power density of 10 mW/cm2,respectively.The SX5 group was sequentiallyexposed to 2.856 and 9.375 GHz microwaves with an average power density of 5 mW/cm2 for 6 min.At 1 and 7 d after exposure,the sperm viability and serum sex hormones were detected by light microscopy and electron microscopy,and testicular tissue structure and oxidative stress and energy metabolism levels were examined.Results The sperm viability,testosterone(T),follicle stimulating hormone(FSH),and inhibin B(INHB)decreased in the S10 and X10 groups at 1 and 7 d after exposure(P＜0.01),and in the SX5 group at 7 d after exposure(P＜0.05).The LH decreased in all the exposure groups at 1 d after exposure(P＜0.01),and increased in the S10 and X10 groups at 7 d after exposure(P＜0.05).The spermatogenic epithelium of testicular tissue was lax,spermatogenic cells were edematous and vacuolated,chromatin condensed and shifted side by side,and the damage was significant in the S10 and X10 groups as compared with the SX5 group.The superoxide dismutase(SOD)activity in testis tissue decreased and malondialdehyde(MDA)content increased at 1 and 7 d after exposure in the S10 group(P＜0.01).In the X10 group,the SOD decreased at 1 d after exposure(P＜0.01).The lactate dehydrogenase(LDH)and succinate dehydrogenase(SDH)activity and adenosine triphosphate(ATP)content in testis tissue decreased at 1 and 7 d after exposure in the S10 and X10 groups(P＜0.05).In the SX5 group,the LDH and SDH decreased at 1 d after exposure(P＜0.05).Conclusion Single and combined exposure to S-band and X-band microwaves can cause damage to male reproductive organs.The S-band causes damage more significantly than that of X-band.Single-frequency microwave high-intensity exposure causes damage more significantly than that of multi-frequency microwave prolonged combined exposure.The damage is closely related to oxidative stress and energy metabolism.

This article reviews the demand, development process, aid types, effects, and existing problems of decision aids for colorectal cancer. The aim is to provide reference for the development of convenient and efficient decision aids for colorectal cancer diagnosis and treatment in China, and to improve the quality of treatment decisions for colorectal cancer patients.

Objective:To study the role of ML-SA5, an agonist of the lysosomal Ca 2+ channel transient receptor potential mucolipin 1 (TRPML1), in promoting lysosomal exocytosis to facilitate intracellular uranium removal and alleviate uranium-induced cellular damage for human renal proximal tubule epithelial cells (HK-2) exposed to uranyl acetate. Methods:HK-2 cells were divided into the following groups to be exposed to uranyl acetate at either 0 or 300 μmol/L for 24 h, followed by treatment with ML-SA5 and/or the lysosomal exocytosis inhibitor vacuolin-1 for 0.5 h: control group (Ctrl group), ML-SA5 group (M group), vacuolin-1 group (V group), ML-SA5 plus vacuolin-1 group (M+ V group), uranium exposure group (U group), uranium exposure plus ML-SA5 group (U+ M group), uranium exposure plus vacuolin-1 group (U+ V group), and uranium exposure plus ML-SA5 plus vacuolin-1 group (U+ M+ V group). We localized lysosome-associated membrane protein-1 (LAMP-1) on the plasma membrane (surface LAMP-1) by immunofluorescence assay; measured intracellular uranium content by inductively coupled plasma mass spectrometry; measured the level of kidney injury molecule-1 (KIM-1) by immunofluorescence assay; measured the rate of cell death with Calcein-AM/PI double staining; determined the subcellular localization of transcription factor EB (TFEB) and the levels of LAMP-1 and TRPML1 proteins by immunofluorescence assay; and measured the number of lysosomes using LysoTracker probes.Results:Compared with the Ctrl group, the U group showed significant increases in the surface LAMP-1 protein level ( t = 12.86, P < 0.05), KIM-1 protein level ( t = 18.86, P < 0.05), cell death rate ( t = 38.53, P < 0.05), TFEB nuclear translocation ( t = 9.12, P < 0.05), the protein expression levels of TFEB’s downstream target genes LAMP-1 ( t = 16.47, P < 0.05) and TRPML1 ( t = 32.33, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 7.75, P < 0.05). Compared with the U group, the U+ M group showed a significantly increased surface LAMP-1 level ( t = 3.33, P < 0.05) and significant decreases in the intracellular uranium level ( t = 5.01, P < 0.05), KIM-1 protein expression level ( t = 3.81, P < 0.05), and cell death rate ( t = 3.24, P < 0.05); all these effects in the U+ M group could be neutralized by the lysosomal exocytosis inhibitor vacuolin-1; and in addition, ML-SA5 significantly increased TFEB nuclear translocation ( t = 9.20, P < 0.05), the protein expression levels of LAMP-1 ( t = 3.05, P < 0.05) and TRPML1 ( t = 3.17, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 3.13, P < 0.05). Conclusions:The TRPML1 agonist ML-SA5 can promote lysosomal exocytosis to enhance intracellular uranium clearance and reduce uranium-induced cellular damage/death in uranium-loaded HK-2 cells, through activating TFEB to up-regulate lysosome biogenesis and TRPML1 protein expression.

Objective:To explore the mechanism of lysosomal membrane permeabilization(LMP)inuranyl acetate-induced death of human kidney proximal tubular epithelial HK-2 cells.Methods:HK-2 cells were exposed to uranyl acetate at concentrations of 100, 300 and 600 μmol/L for 24 h, then in tracellular reactive oxygen species (ROS)and mitochondrial superoxide were measured by DCFH-DA and MitoSOX probe, respectively. HK-2 cells were divided into four groups: blank control group, NAC or CA-074 Me group, uranyl acetate exposure group and uranyl acetate exposure plus NAC or CA-074 Me group. Two-color immune of luorescence staining was used to detect the co-localization of galectin-1 and lysosomal associated membrane protein-1 (LAMP-1) to measure the extent of LMP, and to detect the non- co-localization of cathepsin B and LAMP-1 to reflect the release of cathepsin B in lysosomes. Calcein-AM/PI double staining method was used to detect cell death. One-color immune of luorescence staining of cleaved-caspase-3 expression was used to detect apoptosis. Results:Intracellular ROS and mitochondrial superoxide levels were significantly increased in HK-2 cells after exposure with 100, 300 and 600 μmol/L uranyl acetate for 24 h, about 1.1-2.5 times or 4.0-28 times, respectively( tROS=17.98, 11.84, 11.75, P< 0.05; tmitochondrial superoxide=6.14, 16.02, 13.06, P< 0.05), and they also increased with uranyl acetate concentrations ( tROS=10.10, 10.37, 5.59, P< 0.05; tmitochondrial superoxide=21.50, 15.16, 5.93, P< 0.05). The percentage of co-localization of galectin-1 and LAMP-1 and the percentage of non- co-localization of cathepsin B and LAMP-1 were markedly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, 5.4-6.7 times or 1.5-2.1 times, respectively ( tGalectin-1=15.85, 12.70, P< 0.05; tCathepsin B=5.95, 6.69, P< 0.05), but these increases were inhibited by NAC ( tGalectin-1=4.74, P<0.05; tCathepsin B=4.51, P< 0.05). Moreover, the cell death rate and the cleaved-caspase-3 expression level were also significantly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, about 28-47 times or 2.4-6.0 times, respectively( tPI=30.40, 10.34, P<0.05; tCleaved-caspase-3=18.49, 9.52, P<0.05), and these increases were obviously diminished by CA-074 Me ( tPI= 6.76, P<0.05; tCleaved-caspase-3=13.47, P<0.05). Conclusions:Exposure to uranyl acetate induces a burst of intracellular ROSthat leads to LMP and consequently causes leakage of cathepsin B from lysosomes to cytoplasm, in turn triggering the lysosomal-dependent cell death and mitochondrial-regulated apoptosis of HK-2 cells.