Objective To investigate the clinical characteristics,diagnosis and treatment of ileal injury secondary to percutaneous nephrolithotomy percutaneous nephrolithotomy(PCNL).Methods The diagnosis and treatment of a patient were reviewed,and relevant literature were retrieved.Results The patient was a 41-year-old male,who underwent stage PCNL(initial percutaneous nephrostomy,followed by secondary PCNL)due to right ureteral calculi with severe hydronephrosis.On postoperative day 1,he developed abdominal distension and pain.Abdominal X-ray revealed subdiaphragmatic free gas,and CT showed pelvic and abdominal fluid and gas accumulation,suggesting peritonitis due to intestinal perforation.Emergency exploratory laparotomy identified a 3 mm×3 mm ileal perforation approximately 30 cm from the ileocecal valve,which was repaired surgically.The patient recovered well and was discharged after one week,with no discomfort reported during a 6-month follow-up.Conclusion The clinical features of ileal injury secondary to PCNL include early postoperative abdominal distension,pain and peritonitis.Diagnosis relies on clinical manifestations,abdominal X-ray and CT,with surgical exploration if necessary.Conservative management under vigilant observation can be cautiously adopted for localized injuries,while surgical repair is required for peritonitis or failed conservative therapy.

Objective To explore the molecular mechanism of autophagy mediated by the protein kinase B(AKT)/mammalian target protein of rapamycin(mTOR)pathway in the rehabilitation of muscle atrophy associated with rotator cuff tears(RCTs).Methods Forty male C57BL/6J mice were randomly assigned to the following four groups:sham group,RCTs group,RCTs+exercise group,and RCTs+exercise+rapamycin group,with 10 mice in each group.On the eighth week after grouping,healing of the bone-tendon interface and muscle cell atrophy were analyzed by histology.The mRNA expression levels of muscle-atrophy-related genes(Atrogin-1,Bnip 3,MuRF-1)in supraspinatus muscle tissue were measured by real-time quantitative reverse transcription polymerase chain reaction.The expression of LC3 and AKT/mTOR signal pathway proteins in the supraspinatus muscle tissue of the groups was detected by Western blot,and the degree of autophagy in each group was analyzed by transmission electron microscope.Results Compared with the sham operation group,in RCTs group's maturity score for the bone-tendon interface at the supraspinatus tendon anchorage and the cross-sectional area of the supraspinatus muscle fibers decreased significantly(P＜0.001),while muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1 increased significantly(P＜0.001).Compared with the RCTs group,the RCTs+exercise group showed a significant increase in bone-tendon interface maturity score and cross-sectional area of the supraspinatus muscle fibers(P＜0.01)and a decrease in muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1(P＜0.01).Compared with the sham group,the RCTs group's LC3Ⅰ/LC3Ⅱ and degree of autophagy in the supraspinatus muscle increased significantly(P＜0.001),while p-AKT/AKT and p-mTOR/mTOR expression decreased significantly(P＜0.01).Compared with RCTs group,the RCTs+exercise group's LC3Ⅰ/LC3Ⅱ and degree of autophagy decreased significantly(P＜0.01)and p-AKT/AKT and p-mTOR/mTOR expression increased significantly(P＜0.001).The addition of rapamycin significantly reversed the rehabilitation effect of exercise in the RCTs group.Conclusions This study confirmed the anti-atrophy effect of exercise rehabilitation in RCT diseases and showed that its mechanism is related to AKT/mTOR signal activation,which inhibits autophagy.

Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.

Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P＞0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P＞0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.

Objective To examine the phenotypic characteristics of Ecto-5'-nucleotidase(NtSe/CD73)gene knockout mice in restenosis of blood vessels after vein transplantation so as to identify potential targets for early diagnosis and drug treatment of vascular restenosis after clinical coronary artery bypass surgery.Methods CD73 gene knockout mice aged 8-10 weeks were used as the experimental group,and the littermate wild-type mice were used as the control group.Using the inferior vena cava of mice as a donor,we transplanted to the right carotid artery of allogeneic mice with a trocar method to establish a mouse inferior vena cava carotid artery vascular transplantation model.At the 4th week post-model establishment,we systematically evaluated the patency of the transplanted blood vessels,the formation of the vascular intima,the proliferation of the media,the morphology of the elastin layer,and the expression of inflammatory factors.The vascular smooth muscle cells(VSMCs)from the inferior vena cava of mice were isolated in vitro,and the migration and proliferation were assessed with CD73 inhibitor adenosine 5'-(alpha,beta-methylene)diphosphate(APCP).Results In CD73 knockout mice,neointima formation was impaired,the elastic fiber layer was disrupted and lost,and medial smooth muscle cells proliferated more actively.These changes ultimately led to decreased vascular wall elasticity and increased blood flow resistance.The immunohistochemical staining results suggest that in CD73 gene knockout mice the transplanted vein tissue showed extensive infiltration of Mac-2 positive macrophages,and the expression of cytokines interleukin-1 β(IL-1 β),IL-6,and transforming growth factor β(TGF-β)was significantly increased.CD73 deficiency exacerbated inflammatory responses and vascular remodeling in venous tissues.Scratch wound healing and cell proliferation assays revealed that CD73 inhibition promoted VSMCs proliferation,yet concurrently impaired their migratory capacity.Conclusion Knockout of the CD73 gene exacerbates vascular remodeling and inflammatory response in vein grafts,offering crucial insights for the precise diagnosis and targeted treatment of patients with CD73 gene defects undergoing coronary artery bypass surgery in clinical practice.

Objective To explore the molecular mechanism of autophagy mediated by the protein kinase B(AKT)/mammalian target protein of rapamycin(mTOR)pathway in the rehabilitation of muscle atrophy associated with rotator cuff tears(RCTs).Methods Forty male C57BL/6J mice were randomly assigned to the following four groups:sham group,RCTs group,RCTs+exercise group,and RCTs+exercise+rapamycin group,with 10 mice in each group.On the eighth week after grouping,healing of the bone-tendon interface and muscle cell atrophy were analyzed by histology.The mRNA expression levels of muscle-atrophy-related genes(Atrogin-1,Bnip 3,MuRF-1)in supraspinatus muscle tissue were measured by real-time quantitative reverse transcription polymerase chain reaction.The expression of LC3 and AKT/mTOR signal pathway proteins in the supraspinatus muscle tissue of the groups was detected by Western blot,and the degree of autophagy in each group was analyzed by transmission electron microscope.Results Compared with the sham operation group,in RCTs group's maturity score for the bone-tendon interface at the supraspinatus tendon anchorage and the cross-sectional area of the supraspinatus muscle fibers decreased significantly(P＜0.001),while muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1 increased significantly(P＜0.001).Compared with the RCTs group,the RCTs+exercise group showed a significant increase in bone-tendon interface maturity score and cross-sectional area of the supraspinatus muscle fibers(P＜0.01)and a decrease in muscle loss and the expression of Atrogin-1,Bnip 3,and MuRF-1(P＜0.01).Compared with the sham group,the RCTs group's LC3Ⅰ/LC3Ⅱ and degree of autophagy in the supraspinatus muscle increased significantly(P＜0.001),while p-AKT/AKT and p-mTOR/mTOR expression decreased significantly(P＜0.01).Compared with RCTs group,the RCTs+exercise group's LC3Ⅰ/LC3Ⅱ and degree of autophagy decreased significantly(P＜0.01)and p-AKT/AKT and p-mTOR/mTOR expression increased significantly(P＜0.001).The addition of rapamycin significantly reversed the rehabilitation effect of exercise in the RCTs group.Conclusions This study confirmed the anti-atrophy effect of exercise rehabilitation in RCT diseases and showed that its mechanism is related to AKT/mTOR signal activation,which inhibits autophagy.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

BACKGROUND:The blood-brain barrier is an important structure that protects the central nervous system,and the study of the effects of high glucose on the blood-brain barrier is important for the prevention of high glucose-induced damage to the central nervous system.OBJECTIVE:To investigate the potential effect of high glucose on the blood-brain barrier function of hCMEC/D3 human brain microvascular endothelial cells.METHODS:hCMEC/D3 cells were cultured in regular sugar medium(glucose concentration of 25 mmol/L)and high-sugar medium(glucose concentration of 55 mmol/L).The morphology of cells in each group was observed by light microscopy.CCK-8 assay was used to detect changes in cell viability.A monolayer blood-brain barrier model was established using hCMEC/D3 cell line with Transwell chamber device.Changes in cell transmembrane resistance were monitored daily.The permeability of cell monolayers was detected by phenol red permeability.Flow cytometry was used to detect the apoptosis rate of the cells.Western blot assay was used to detect the expression of Bcl-2,Bax,Caspase-3,ZO-1,Occludin,Claudin-1,and histone deacetylase 4.The levels of histone deacetylase in cell supernatant were detected by ELISA.The expression of histone deacetylase 4 in cells was detected by immunofluorescence.RESULTS AND CONCLUSION:(1)The cell viability of high sugar group was significantly lower than that of control group(P＜0.000 1).(2)The cells of the control group were in a good growth state,interwoven into a dense mesh,with interconnections between synapses.The cell growth of high glucose group was suppressed,and the connection of inter-cellular synapses was reduced.(3)Compared with the control group,the transmembrane resistance value of the high glucose group was reduced(P＜0.05);phenol-red permeability of the monolayer cell membrane was increased(P＜0.05);cell apoptosis rate was increased(P＜0.01);the expression of Bax protein was increased(P＜0.000 1);the expression of Caspase-3 protein had no significant change(P＞0.05);the expression of Bcl-2,ZO-1,Occludin,Claudin-1,and histone deacetylase 4 proteins was decreased(P＜0.01,P＜0.001,P＜0.01,P＜0.000 1,P＜0.01);the fluorescence expression of histone deacetylase 4 was decreased(P＜0.001)in the high glucose group.(4)The level of histone deacetylase 4 in the cell supernatant of the high glucose group was lower than that of the control group(P＜0.05).The results show that high glucose induces the increased apoptosis and enhances permeability of hCEMCE/D3 cells,and its mechanism may be related to the decreased expression level of histone deacetylase 4.

BACKGROUND:Sarcopenia is a comprehensive condition of aging induced decline in skeletal muscle mass and strength and represents a major health challenge for the elderly.Accumulating evidence suggests that mitochondrial dysfunction plays a key role in the pathogenesis of sarcopenia.OBJECTIVE:To summarize the mechanisms by which dysregulation of mitochondrial quality control leads to sarcopenia and to explore whether mitochondrial transplantation may be a potential target for the treatment of sarcopenia.METHODS:We searched PubMed and CNKI databases for relevant articles published from 2009 to 2023 using the keywords "sarcopenia,mitochondrial dysfunction,mitochondrial quality control,mitochondrial transplantation,limitations."RESULTS AND CONCLUSION:Given the key role of mitochondrial dysfunction in the pathogenesis of sarcopenia,mitochondrial transplantation may serve as a possible strategy for the treatment of sarcopenia by improving mitochondrial bioenergetics and modulating mitochondria related signaling pathways.Although some preclinical and clinical studies have confirmed the potential of mitochondrial transplantation for the treatment of various diseases,there are still some urgent questions regarding the specific details of mitochondrial transfer.

Objective:To investigate the effect of phosphorus-containing replacement solution for the prevention and treatment of hypophosphatemia during continuous renal replacement therapy (CRRT) in critically ill patients with blood phosphorus level ≤1.45 mmol/L, and to provide clinical reference.Methods:It was a historical prospective cohort study. The critically ill patients receiving CRRT with blood phosphorus ≤ 1.45 mmol/L in the intensive care unit of Henan Provincial People's Hospital from October 2021 to January 2023 and from April 2023 to January 2024 was selected as the study subjects. The patients were divided into test group (from April 2023 to January 2024) and control group (from October 2021 to January 2023) according to whether phosphate (1.0 mmol/L) was added to the replacement solution during CRRT, and the differences of clinical data before and after CRRT between the two groups were compared. The patients were divided into hypophosphatemia group and non-hypophosphatemia group according to whether blood phosphorus < 0.81 mmol/L within 24 h after the end of CRRT, and the differences of clinical data between the two groups were compared. Logistic regression analysis was used to analyze the related factors of hypophosphatemia.Results:A total of 149 critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT were enrolled in the study, with age of 64(47, 75) years and 87 males (58.4%). Among 149 patients, 84(56.4%) had hypophosphatemia after CRRT, and no hyperphosphatemia occurred. The incidence of hypophosphatemia in test group and control group was 40.0% (30/75) and 73.0% (54/74), respectively. There was no statistically significant difference in baseline clinical data before CRRT between test group and control group (all P>0.05). C-reactive protein ( Z=-3.356, P=0.001), blood calcium ( Z=-3.835, P<0.001) and proportion of hypophosphatemia ( χ2=16.467, P<0.001) in the test group were lower than those in the control group, and blood phosphorus ( Z=3.886, P<0.001) in the test group was higher than that in the control group within 24 h after CRRT. Compared with non-hypophosphatemia group, the proportion of parenteral nutrition ( χ2=6.802, P=0.009) and blood calcium within 24 h after CRRT ( Z=-2.515, P=0.012) in the hypophosphatemia group were higher, and blood phosphorus within 24 h after CRRT ( Z=-10.451, P<0.001), blood phosphorus after 24 h after CRRT treatment ( Z=-5.331, P<0.001) and the proportion of applied replacement solution containing phosphorus ( χ2=16.467, P<0.001) in the hypophosphatemia group were lower. The results of multivariate logistic regression analysis showed that parenteral nutrition ( OR=2.521, 95% CI 1.228-5.175, P=0.012) and application of phosphorus- containing replacement solution ( OR=0.241, 95% CI 0.119-0.491, P<0.001) were independent relevant factors of hypophosphatemia after CRRT in the whole cohort of patients. Conclusions:The application of phosphorus-containing replacement solution in critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT is safe and effective, and the incidence of hypophosphatemia is low. Application of phosphorus-containing replacement solution in critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT can reduce the incidence risk of hypophosphatemia after CRRT.