Osteosarcopenia is a geriatric syndrome referring to the co-existence of osteoporosis and sarcopenia.Its pathogenesis involves factors such as genetics, mechanics of the musculoskeletal system, endocrine regulatory mechanisms and molecular signaling pathways.In clinical practice, aside from comprehensive assessment of risk factors, screening of bone density, muscle strength, muscle mass and the overall body function must also be undertaken.Intervention measures primarily include therapeutic exercise, nutritional support and drugs.

Objective:To investigate the therapeutic impact of combining vitamin D supplementation with dietary adjustments on elderly male patients with diabetes and osteosarcopenia.Methods:From January 2021 to May 2023, a total of 108 male patients diagnosed with diabetes and osteosarcopenia were admitted to Beijing hospital for research purposes.The patients were randomly assigned to either a control group( n=54)or a trial group( n=54).The control group received conventional dietary adjustments, while the trial group received vitamin D supplementation in addition to dietary adjustments.Various parameters including 25-(OH)-VitD 3 levels, blood glucose levels, appendicular skeletal muscle mass index(ASMI), bone mineral density, and bone metabolism indexes were measured before and after the treatment in both groups. Results:Compared to the pre-treatment period, the levels of 25-(OH)-VitD 3, grip strength, 6 m step speed, and ASMI increased in both groups, while fasting blood glucose and 2 h postprandial blood glucose decreased significantly(all P<0.05).Additionally, the experimental group showed higher levels of 25-(OH)-VitD 3, grip strength, 6 m step speed, and ASMI compared to the control group post-treatment, with lower levels of fasting blood glucose and 2 h postprandial blood glucose(all P<0.05).Compared with the pre-treatment period (bone density values in the lumbar spine: 0.41±0.09, the hip: 0.42±0.12 in the control group; bone density values in the lumbar spine: 0.43±0.07, the hip: 0.44±0.09 in the experimental group), the bone density values of the lumbar spine and the hip were higher in both groups after treatment(bone density values in the lumbar spine: 0.76±0.12, the hip: 0.78±0.12 in the control group; bone density values in the lumbar spine: 0.95±0.22, the hip: 0.97±0.28 in the experimental group). The bone density values of the lumbar spine and the hip in the experimental group were higher than those of the control group after treatment(all P<0.05).Furthermore, serum concentrations of parathyroid hormone(PTH)and osteoclast differentiation factor(RANKL)were significantly lower, while serum osteocalcin(OCN)was significantly higher in both groups post-treatment(all P<0.05).In the experimental group, serum PTH and RANKL concentrations were significantly lower and serum OCN was significantly higher compared to the control group post-treatment(all P<0.05). Conclusions:The results show that incorporating vitamin D into dietary changes can effectively regulate blood glucose levels, decrease bone loss, enhance bone density, and improve muscle quality in this patient population.

Objective:To evaluate the prognostic value of sepsis-induced coagulopathy (SIC) in patients with sepsis.Methods:From January 2019 to December 2021, patients with sepsis admitted to the Intensive Care Unit of our hospital were retrospectively classified into the SIC group and non-SIC group according to SIC diagnostic criteria. The baseline clinical data, severity score, total length of hospital stay, length of ICU stay and 28-day survival were compared between the two groups. Kaplan-Meier was used to compare the 28-day survival of patients with sepsis between the two groups. Cox proportional hazard regression model was employed to analyze the risk factors of prognosis in patients with sepsis.Results:Totally 274 patients with sepsis were included in the analysis, including 139 patients in the SIC group and 135 patients in the non-SIC group. The two groups were compared in the perspectives of the Platelet count (PLT), prothrombin time (PT) , procalcitonin (PCT), D dimer, hematocrit, red blood cell distribution width, hemoglobin, acute kidney injury (AKI), the use of continuous renal replacement treatment (CRRT), the use of vasoactive drugs, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHEⅡ) score were compared between the two groups and the difference were statistically different (all P<0.05). Kaplan-Meier analysis showed that the 28-day mortality rate in the SIC group was significantly higher than that in the non-SIC group (32.4% vs. 14.1%, P<0.05). COX proportional hazard model showed that SIC score ( HR= 2.17, 95% CI: 1.15-3.91, P<0.05), APACHEⅡ score ( HR= 1.13, 95% CI: 1.09-1.17, P<0.05) and the use of vasoactive drugs ( HR=3.66, 95% CI: 1.53-8.75, P<0.05) were independent influencing factors for 28-day death in patients with sepsis. Conclusions:Patients with sepsis and SIC have more severe disease and increased mortality risk. SIC score exhibits good clinical value in predicting the prognosis of patients with sepsis.

ObjectiveTo investigate the Alzheimer-associated neurofilament protein （AD7c-NTP） in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay （ELISA）， and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL， the objects was divided into normal group （n=956） and elevated group （n=194）. Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60（0.30~1.20） ng/mL. The urine AD7c-NTP level was higher in women than that in men ［1.04（0.40~1.30） ng/mL vs. 0.84（0.30~1.00） ng/mL， Z=4.202， P˂0.01］. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group ［0.50（0.30~0.90） ng/mL vs. 2.10（1.70~2.10） ng/mL， Z=22.035， P˂0.01］. The results of the univariate comparison showed that， the differences between the two groups in age （Z=6.545）， fasting glucose （Z=3.506）， blood uric acid （Z=2.574）， urea nitrogen （Z=2.891）， creatinine （Z=2.243）， total bilirubin （Z=3.936）， glutathione （Z=0.969）， total cholesterol （t=3.956） and low density lipoprotein （Z=-5.678） were were statistically significant （P˂0.05 or 0.01）. Spearman correlation analysis showed that， the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen， glucose， total cholesterol and low density lipoprotein （r=0.177， 0.178， 0.171， 0.109， 0.149， P˂0.01）， and negatively correlated with the level of total bilirubin （r=-0.172， P˂0.01）. Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age， urea nitrogen， glucose， total cholesterol and low density lipoprotein， and negatively correlated with total bilirubin.

Vibrio parahaemolyticus, the main pathogen causing seafood related food poisoning worldwide, has strong biofilm formation ability. ToxR is a membrane binding regulatory protein, which has regulatory effect on biofilm formation of V. parahaemolyticus, but the specific mechanism has not been reported. c-di-GMP is an important second messenger in bacteria and is involved in regulating a variety of bacterial behaviors including biofilm formation. In this study, we investigated the regulation of ToxR on c-di-GMP metabolism in V. parahaemolyticus. Intracellular c-di-GMP in the wild type (WT) and toxR mutant (ΔtoxR) strains were extracted by ultrasonication, and the concentrations of c-di-GMP were then determined by enzyme linked immunosorbent assay (ELISA). Three c-di-GMP metabolism-related genes scrA, scrG and vpa0198 were selected as the target genes. Quantitative real-time PCR (q-PCR) was employed to calculate the transcriptional variation of each target gene between WT and ΔtoxR strains. The regulatory DNA region of each target gene was cloned into the pHR309 plasmid harboring a promoterless lacZ gene. The recombinant plasmid was subsequently transferred into WT and ΔtoxR strains to detect the β-galactosidase activity in the cellular extracts. The recombinant lacZ plasmid containing each of the target gene was also transferred into E. coli 100λpir strain harboring the pBAD33 plasmid or the recombinant pBAD33-toxR to test whether ToxR could regulate the expression of the target gene in a heterologous host. The regulatory DNA region of each target gene was amplified by PCR, and the over-expressed His-ToxR was purified. The electrophoretic mobility shift assay (EMSA) was applied to verify whether His-ToxR directly bound to the target promoter region. ELISA results showed that the intracellular c-di-GMP level significantly enhanced in ΔtoxR strain relative to that in WT strain, suggesting that ToxR inhibited the production of c-di-GMP in V. parahaemolyticus. qPCR results showed that the mRNA levels of scrA, scrG and vpa0198 significantly increased in ΔtoxR strain relative to those in WT strain, suggesting that ToxR repressed the transcription of scrA, scrG and vpa0198. lacZ fusion assay showed that ToxR was able to repress the promoter activities of scrA, scrG and vpa0198 in both V. parahaemolyticus and E. coli 100λpir. EMSA results showed that His-ToxR was able to bind to the regulatory DNA regions of scrA and scrG, but not to the regulatory DNA region of vpa0198. In conclusion, ToxR inhibited the production of c-di-GMP in V. parahaemolyticus via directly regulating the transcription of enzyme genes associated with c-di-GMP metabolism, which would be beneficial for V. parahaemolyticus to precisely control bacterial behaviors including biofilm formation.
Vibrio parahaemolyticus/metabolism* ; Escherichia coli/metabolism* ; Bacterial Proteins/metabolism* ; Transcription Factors/genetics* ; Gene Expression Regulation, Bacterial

Objective:To explore the impact of urinary iodine concentration (UIC) on response to 131I treatment in differentiated thyroid cancer (DTC) patients with different risk stratifications. Methods:A total of 181 patients with DTC (75 males, 106 females, age: (44.1±12.5) years), who received the first 131I treatment in Tianjin Medical University General Hospital between January 2018 and February 2019, were retrospectively analyzed. Patients were divided into low- to intermediate-risk and high-risk groups. The treatment response was categorized into excellent response (ER) and non-excellent response (non-ER). Factors being evaluated including age, sex, preablative stimulated thyroglobulin (ps-Tg), UIC, etc. Mann-Whitney U test, χ2 test and logistic regression analysis were used for data analysis. Results:The UIC and ps-Tg in the low- to intermediate-risk group ( n=113) was 111.60(55.80, 204.65) μg/L and 2.08(0.63, 4.91) μg/L, respectively. Compared with the ER subgroup ( n=86), non-ER subgroup ( n=27) had higher UIC and ps-Tg level ( z values: -2.585, -4.511, both P<0.05). In the high-risk group ( n=68), UIC was 115.40(61.23, 167.28) μg/L and ps-Tg was 16.65(4.52, 43.45) μg/L. Compared with the ER subgroup ( n=20), non-ER subgroup ( n=48) had higher ps-Tg level ( z=-4.677, P<0.01), while the UIC was not significantly different between ER and non-ER subgroups ( z=-0.013, P>0.05). The multivariate logistic analysis indicated the ps-Tg level was the significant variable for non-ER in low- to intermediate-risk group (odds ratio( OR)=6.157(95% CI: 1.046-36.227); OR=22.965(95% CI: 3.591-146.857), both P<0.05) and high-risk group ( OR=9.696 (95% CI: 1.379-68.169), P<0.05); a high UIC could be an indicator of non-ER only in the low- to intermediate-risk group ( OR=3.715(95% CI: 1.201-11.488), P<0.05). Conclusions:The non-ER is associated with UIC in the low- to intermediate-risk group; however, UIC does not affect the non-ER in the high-risk group. Higher ps-Tg level is associated with non-ER in patients with low- to intermediate-risk and high-risk DTC.

Objective:To investigate the prognostic factors of differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibody (TgAb) and varying ages after operation and 131I treatment. To explore the value of TgAb level and its change in the prognosis of DTC patients. Methods:Clinical data of 131 TgAb positive DTC patients were retrospectively analyzed. According to age, they were divided into young group(age<55 years, n=95) and elder group (age≥55 years, n=36). According to response, it was divided into excellent response group (110 cases) and non-excellent response group (21 cases). χ2 test and t test were used to compare the clinicopathological features between excellent response group and non-excellent response group. By logistic regression analysis, the independent risk factors affecting the prognosis of patients were analyzed. The receiver operating characteristic curve was used to determine the TgAb value of persistent or recurrent DTC, and the Kaplan-Meier regression curve was used to analyze the time of TgAb becoming negative. P<0.05 was statistically significant. Results:In young patients, the higher serum TgAb level before 131I treatment and the lateral lymph node metastasis were the independent influencing factors of poor prognosis [ OR=0.89(95% CI 0.83-0.95), OR=0.15(95% CI 0.05-0.52); both P<0.05]. In elder group, extraglandular invasion and higher serum TgAb before 131I treatment were associated with poorer prognosis [ OR=0.05(95% CI 0-0.83), OR=0.91(95% CI 0.76-1.13); P<0.05]. The serum TgAb thresholds for predicting DTC persistence/recurrence were 315.5 IU/mL(246.0 IU/mL in the young group and 516.5 IU/mL in the elder group). The mean time TgAb sera turned negative was (26.37±2.22) months [(23.28±2.37) months for young group and (32.64±4.07) months for elder group]. The TgAb decreased >50% in one year of the patients who had a lower probability of disease persistence/recurrence than the group without ( P<0.05). Conclusions:The high level of serum TgAb before 131I treatment and lateral lymph node metastasis were independent factors of poor prognosis in young patients, while in elder patients, extraglandular tumor invasion and the high level of serum TgAb before 131I treatment were independent factors of poor prognosis. The rate of TgAb change one year after treatment may be used as an early marker for predicting the disease status of TgAb positive patients.

Objective:To study the transcriptional regulation of pilABCD by the master quorum sensing (QS) regulator OpaR in Vibrio parahaemolyticus. Methods:Total RNAs were extracted from the wild type (WT) and opaR mutant (Δ opaR) strain. Quantitative real-time PCR (qPCR) was employed to calculate the transcriptional variation of pilA (the first gene of pilABCD operon) between WT and Δ opaR. The regulatory DNA region of pilABCD was cloned into the corresponding restriction endonuclease sites of pHRP309 harboring a promoterless lacZ reporter gene. The recombinant pHRP309 plasmid was then transferred into WT and Δ opaR, respectively, to detect the β-galactosidase activity in cellular extracts using a β-Galactosidase Enzyme Assay System (Promega). The primer extension assay was applied to map the transcription start site of pilABCD using the total RNAs extracted from the WT strain as the template. The regulatory DNA region of pilABCD was amplified by PCR, and the over-expressed His-OpaR was purified under native conditions with nickel loaded HiTrap Chelating Sepharose columns (Amersham). Thereafter, the electrophoretic mobility shift assay (EMSA) was applied to analyze the DNA-binding activity of His-OpaR to the target DNA in vitro, and the DNase I footprinting assay was further employed to detect the DNA-binding sites of His-OpaR within the target DNA. Results:The results of qPCR and LacZ fusion assays showed that OpaR activated the transcription of pilABCD, leading to a gradual increase in the expression level of pilA with the extension of culture time. The primer extension assay detected only one transcription start site located at 155 bp upstream of pilA. The results of EMSA and DNase Ⅰ footprinting assays showed that His-OpaR protected two DNA regions located from -246 to -197 bp and -181 to -131 bp upstream of pilA. Conclusions:Vibrio parahaemolyticus OpaR activated the transcription of pilABCD in a direct manner.

OBJECTIVE: To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation. METHODS: A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation. RESULTS: The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% 96.0%, 94.1% 93.9%, and 90.6% 93.9%, respectively; > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% 96.0%, 90.8% 87.2%, and 79.0% 82.3%, respectively; > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms ( > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation ( < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group ( < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration ( < 0.05). CONCLUSIONS In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.
Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Polycystic Kidney, Autosomal Dominant ; Retrospective Studies

Objective To investigate the radioactivity distribution of 131 I-bovine serum albumin ( BSA )-mesoporous silica nanoparticles ( MSNs )-anti-vascular endothelial growth factor receptor 2 (VEGFR2) in anaplastic thyroid carcinoma (ATC) and to explore its antitumor efficacy in ATC-bearing nude mouse models. Methods 131 I-BSA-MSNs-anti-VEGFR2 and 131 I-BSA-MSNs were constructed. FRO tumor xenografts were established and the SPECT/CT images of tumor-bearing mice were acquired at differ-ent time points after intratumoral injection with 131 I-BSA-MSNs-anti-VEGFR2 ( targeting group) , 131 I-BSA-MSNs ( non-targeting group) , Na131 I ( Na131 I group) and saline ( control group) , respectively. The changes of body mass and tumor volume in each group were recorded. Two-sample t test and log-rank test were used to analyze the data. Results After incubation for 3 h, the fluorescence intensity in targeting group was higher than that in non-targeting group (345.26±16.35 vs 280.61±9.65;t=5.90, P<0.05). After injection for 1-3 weeks, the radioactivity detected by SPECT/CT in targeting group was obviously stronger than that in non-targeting group ( t values:7.060-12.780, all P<0.05) . At the end of the observation, the tumor vol-ume of Na131I group, control group, non-targeting group and targeting group increased to (278.3±19.3)％, (296.6±24.2)％, (198.7±13.2)％ and (103.7±6.2)％ of the original volume, respectively. The body mass of the first 2 groups decreased to (88.6±3.0)％ and (86.2±3.1)％ of the original body mass respec-tively, while that of the latter 2 groups increased to (102.1±3.1)％ and (116.2±3.4)％ of the original body mass respectively. Survival analysis showed that the median survival time in targeting group ( 38 d) was sig-nificantly longer than that in non-targeting group (34 d;χ2=8.05, P<0.05). Conclusion 131I-BSA-MSNs-anti-VEGFR2 can effectively inhibit the tumor growth of ATC and prolong the survival of tumor-bearing nude mice, which gives a good suggestion for the treatment and prognosis evaluation of ATC.