Objective:To investigate the regulatory effect of follistatin-like 1 protein (FSTL1) on the differentiation of mesenchymal stem cells (MSCs) into myofibroblasts in renal tissue and on renal fibrosis induced by renal ischemia-reperfusion injury (IRI).Method:In animal experiments, a unilateral renal IRI-induced fibrosis model was established by clamping the left renal pedicle (IRI 7 d group, n=3), with a sham-operated group as control (Sham 7 d group, n=3). Twelve male C57BL/6 mice were randomly assigned to sham operation (Sham group, n=4), model (IRI group, n=4) and FSTL1 treatment (IRI+FSTL1 group, n=4) groups. The Sham group underwent laparotomy sham surgery, while the IRI group and IRI+FSTL1 group underwent unilateral renal IRI surgery. From 1 day before surgery to 7 days after surgery, mice received daily intraperitoneal injections of phosphate buffered saline (Sham group and IRI group) or recombinant FSTL1 protein (IRI+FSTL1 group). The mice were sacrificed 14 days after surgery. Renal histopathological damage was evaluated by hematoxylin-eosin (HE) staining. Collagen fiber deposition and fibronectin (FN) accumulation in renal interstitium were assessed by Sirius red staining, Masson’s trichrome staining and immunohistochemical staining. The co-expression level of stem cell antigen-1 (SCA-1) and α-smooth muscle actin (α-SMA) was detected by double immunofluorescence staining. The mRNA expression levels of fibrosis-related genes ( Col1a1, Col3a1, Fn1) and myofibroblast marker gene ( Acta2) were detected by real time quantitative polymerase chain reaction (RT-qPCR). In cell experiments, a differentiation model of mouse MSCs into myofibroblasts was established through TGF-β1 induction (MSC+TGF-β1 group, n=3), with a blank control group (MSC group, n=3) set up for comparison. Bone marrow MSCs from C57BL/6 mice were randomly divided into 4 groups: the TGF-β1 induction group (MSC+TGF-β1, n=6), the FSTL1 treatment group (MSC+TGF-β1+FSTL1, n=6), the negative control siRNA transfection group (MSC-siNC+TGF-β1, n=6), and the Fstl1-targeted siRNA transfection group (MSC-si Fstl1+TGF-β1, n=6). The mRNA and protein expression levels of Col1a1, Col3a1, Fn1 and Acta2 were detected by RT-qPCR and Western blot respectively. The concentration of FSTL1 protein in cell culture supernatant was measured by enzyme-linked immunosorbent assay. Result:The expression of Col1a1 and Acta2 mRNA in the kidney tissue of IRI 7 d group mice was higher than that of the Sham 7 d group (both P<0.05), successfully establishing a mouse model of renal fibrosis. The mRNA expression of Fstl1 in kidney tissues of the IRI 7 d group mice was upregulated ( P<0.01). Immunofluorescence double staining revealed increased co-expression of SCA-1/α-SMA and SCA-1/FSTL1 in the renal interstitium. At 14 days after surgery, HE staining results showed reduced pathological damage in kidney tissues of the IRI+FSTL1 group compared to the IRI group, and Sirius Red and Masson staining revealed decreased collagen fiber deposition in the renal interstitium, while immunohistochemical staining demonstrated reduced FN accumulation in the renal interstitium (all P<0.05). The mRNA expression levels of Col1a1, Col3a1, Fn1 and Acta2 in renal tissue of IRI+FSTL1 group were lower than IRI group (all P<0.05). Double immunofluorescence staining showed a decrease in the co-expression of SCA-1 and α-SMA in renal interstitium. In cell experiments, the mRNA expression levels of Col1a1, Col3a1, Fn1, and Acta2 in the MSC+TGF-β1 group were higher than those in the MSC group (all P<0.05), confirming successful TGF-β1-induced myofibroblast differentiation of MSCs. Additionally, both intracellular FSTL1 protein expression and FSTL1 protein concentration in the cell supernatant were elevated in the MSC+TGF-β1 group (both P<0.05). Compared with MSC+TGF-β1 group, the mRNA levels of Acta2 and Col1a1 in MSC+TGF-β1+FSTL1 group were decreased (both P<0.01), and the protein expression levels of collagen Ⅰ and α-SMA were significantly decreased (both P<0.001). Compared with MSC-siNC+TGF-β1 group, the protein level of FSTL1 in cell culture supernatant of MSC-si Fstl1+TGF-β1 group were decreased ( P<0.001), while the protein expression levels of FN and α-SMA were increased (both P<0.001), and the mRNA expression levels of Fn1 and Acta2 were increased (both P<0.05). Conclusions:During unilateral renal IRI-induced renal fibrosis, MSCs in renal interstitium may differentiate into myofibroblasts. FSTL1 may alleviate renal fibrosis after unilateral renal IRI by inhibiting the differentiation of MSCs into myofibroblasts.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the impact of donor kidney histopathological lesions on the risk of BK virus (BKV) infection and progression after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 326 kidney transplant recipients from deceased donors at the Department of Kidney Transplantation, the First Affiliated Hospital of Zhengzhou University, from January 2019 to June 2020. The recipients were divided into two groups based on whether BKV infection occurred after kidney transplantation: the BKV infection group (145 cases) and the non-BKV infection group (181 cases). The correlation between donor kidney histopathological findings from zero-hour biopsy and BKV infection, as well as the impact on the risk and progression of BKV infection, was analyzed. Results The incidence of BKV infection among the 326 kidney transplant recipients was 44.5% (145/326). The clearance rate of BKV after infection was 82.1% (119/145), while 17.9% (26/145) progressed to BKV viremia. Among the 326 qualified kidney biopsy specimens, 32 cases showed mild tubular atrophy, 324 cases had mild acute tubular injury, 27 cases exhibited mild hyaline arteriosclerosis, 10 cases had moderate to severe hyaline arteriosclerosis, 7 cases showed mild interstitial inflammation, 23 cases had mild interstitial fibrosis, 6 cases exhibited mild arterial intimal fibrosis, and 1 case had moderate to severe arterial intimal fibrosis. Multivariate logistic regression analysis revealed that male recipients, donor age and tubular atrophy were independent risk factors for BKV infection (all P<0.05). Tubular atrophy was also an independent risk factor for the progression from BKV uria to BKV viremia (P<0.05). Conclusions Donor kidney histopathological lesions have a certain impact on BKV infection and progression after kidney transplantation. Patients with more severe tubular atrophy in donor kidneys have a higher risk of BKV infection after kidney transplantation and are more likely to progress to BKV viremia.

OBJECTIVE To investigate the prevalence of plasma vitamin B1 deficiency in patients with sepsis and analyze the relationship between plasma vitamin B1 levels and lactic acidosis.METHODS A total of 40 patients with sepsis and 42 patients with sepsis shock admitted to the intensive care unit(ICU)of General Hospital of Ningxia Medical University from Nov.2020 to Nov.2022 were selected as the study objects.Volunteers matched by age,gender and body mass index(BMI)were selected as the healthy group.Data on gender,age,BMI,under-lying diseases,sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,infection site,duration of mechanical ventilation and ICU length of stay were collected.La-boratory tests including blood routine,electrolytes,blood lactate(Lac),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),blood urea nitrogen(BUN)and serum creatinine(Scr)were performed in both groups.Plasma samples from both disease group and the healthy group were collected.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to measure plasma thiamine(vitamin B1)levels in the disease group on the first,third and fifth days,respectively,as well as in the healthy group.RESULTS On the first day of admission,both the sepsis group and the septic shock group exhibited vitamin B1 de-ficiency.Specifically,6 cases of vitamin B1 deficiency were observed in the patients with sepsis,while 8 cases of vitamin B1 deficiency were noted in the patients with septic shock(P=0.640).By the third and fifth days,the proportions of vitamin B1 deficiency in the sepsis group were 22.50％and 42.50％,respectively,whereas in the septic shock group,these proportions were high at 26.19％and 54.76％,with a statistically significant difference(P＜0.05).On the fifth day,in the normal liver function group,vitamin B1 levels showed a negative correlation with lactate(r=-0.590,P=0.005),whereas in the abnormal liver function group,vitamin B1 levels were pos-itively correlated with lactate(r=0.678,P=0.017).The patients in the septic shock group had low K+and ALB levels[(2.60±0.42)mmol/L and(24.56±5.78)g/L,respectively]compared to those in the sepsis group(P＜0.05).CONCLUSIONS Plasma vitamin B1 deficiency is prevalent among patients with sepsis.Changes in plasma vitamin B1 levels are closely associated with blood lactate levels in these patients.

OBJECTIVE To investigate the prevalence of plasma vitamin B1 deficiency in patients with sepsis and analyze the relationship between plasma vitamin B1 levels and lactic acidosis.METHODS A total of 40 patients with sepsis and 42 patients with sepsis shock admitted to the intensive care unit(ICU)of General Hospital of Ningxia Medical University from Nov.2020 to Nov.2022 were selected as the study objects.Volunteers matched by age,gender and body mass index(BMI)were selected as the healthy group.Data on gender,age,BMI,under-lying diseases,sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,infection site,duration of mechanical ventilation and ICU length of stay were collected.La-boratory tests including blood routine,electrolytes,blood lactate(Lac),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),blood urea nitrogen(BUN)and serum creatinine(Scr)were performed in both groups.Plasma samples from both disease group and the healthy group were collected.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to measure plasma thiamine(vitamin B1)levels in the disease group on the first,third and fifth days,respectively,as well as in the healthy group.RESULTS On the first day of admission,both the sepsis group and the septic shock group exhibited vitamin B1 de-ficiency.Specifically,6 cases of vitamin B1 deficiency were observed in the patients with sepsis,while 8 cases of vitamin B1 deficiency were noted in the patients with septic shock(P=0.640).By the third and fifth days,the proportions of vitamin B1 deficiency in the sepsis group were 22.50％and 42.50％,respectively,whereas in the septic shock group,these proportions were high at 26.19％and 54.76％,with a statistically significant difference(P＜0.05).On the fifth day,in the normal liver function group,vitamin B1 levels showed a negative correlation with lactate(r=-0.590,P=0.005),whereas in the abnormal liver function group,vitamin B1 levels were pos-itively correlated with lactate(r=0.678,P=0.017).The patients in the septic shock group had low K+and ALB levels[(2.60±0.42)mmol/L and(24.56±5.78)g/L,respectively]compared to those in the sepsis group(P＜0.05).CONCLUSIONS Plasma vitamin B1 deficiency is prevalent among patients with sepsis.Changes in plasma vitamin B1 levels are closely associated with blood lactate levels in these patients.

Objective:To investigate the regulatory effect of follistatin-like 1 protein (FSTL1) on the differentiation of mesenchymal stem cells (MSCs) into myofibroblasts in renal tissue and on renal fibrosis induced by renal ischemia-reperfusion injury (IRI).Method:In animal experiments, a unilateral renal IRI-induced fibrosis model was established by clamping the left renal pedicle (IRI 7 d group, n=3), with a sham-operated group as control (Sham 7 d group, n=3). Twelve male C57BL/6 mice were randomly assigned to sham operation (Sham group, n=4), model (IRI group, n=4) and FSTL1 treatment (IRI+FSTL1 group, n=4) groups. The Sham group underwent laparotomy sham surgery, while the IRI group and IRI+FSTL1 group underwent unilateral renal IRI surgery. From 1 day before surgery to 7 days after surgery, mice received daily intraperitoneal injections of phosphate buffered saline (Sham group and IRI group) or recombinant FSTL1 protein (IRI+FSTL1 group). The mice were sacrificed 14 days after surgery. Renal histopathological damage was evaluated by hematoxylin-eosin (HE) staining. Collagen fiber deposition and fibronectin (FN) accumulation in renal interstitium were assessed by Sirius red staining, Masson’s trichrome staining and immunohistochemical staining. The co-expression level of stem cell antigen-1 (SCA-1) and α-smooth muscle actin (α-SMA) was detected by double immunofluorescence staining. The mRNA expression levels of fibrosis-related genes ( Col1a1, Col3a1, Fn1) and myofibroblast marker gene ( Acta2) were detected by real time quantitative polymerase chain reaction (RT-qPCR). In cell experiments, a differentiation model of mouse MSCs into myofibroblasts was established through TGF-β1 induction (MSC+TGF-β1 group, n=3), with a blank control group (MSC group, n=3) set up for comparison. Bone marrow MSCs from C57BL/6 mice were randomly divided into 4 groups: the TGF-β1 induction group (MSC+TGF-β1, n=6), the FSTL1 treatment group (MSC+TGF-β1+FSTL1, n=6), the negative control siRNA transfection group (MSC-siNC+TGF-β1, n=6), and the Fstl1-targeted siRNA transfection group (MSC-si Fstl1+TGF-β1, n=6). The mRNA and protein expression levels of Col1a1, Col3a1, Fn1 and Acta2 were detected by RT-qPCR and Western blot respectively. The concentration of FSTL1 protein in cell culture supernatant was measured by enzyme-linked immunosorbent assay. Result:The expression of Col1a1 and Acta2 mRNA in the kidney tissue of IRI 7 d group mice was higher than that of the Sham 7 d group (both P<0.05), successfully establishing a mouse model of renal fibrosis. The mRNA expression of Fstl1 in kidney tissues of the IRI 7 d group mice was upregulated ( P<0.01). Immunofluorescence double staining revealed increased co-expression of SCA-1/α-SMA and SCA-1/FSTL1 in the renal interstitium. At 14 days after surgery, HE staining results showed reduced pathological damage in kidney tissues of the IRI+FSTL1 group compared to the IRI group, and Sirius Red and Masson staining revealed decreased collagen fiber deposition in the renal interstitium, while immunohistochemical staining demonstrated reduced FN accumulation in the renal interstitium (all P<0.05). The mRNA expression levels of Col1a1, Col3a1, Fn1 and Acta2 in renal tissue of IRI+FSTL1 group were lower than IRI group (all P<0.05). Double immunofluorescence staining showed a decrease in the co-expression of SCA-1 and α-SMA in renal interstitium. In cell experiments, the mRNA expression levels of Col1a1, Col3a1, Fn1, and Acta2 in the MSC+TGF-β1 group were higher than those in the MSC group (all P<0.05), confirming successful TGF-β1-induced myofibroblast differentiation of MSCs. Additionally, both intracellular FSTL1 protein expression and FSTL1 protein concentration in the cell supernatant were elevated in the MSC+TGF-β1 group (both P<0.05). Compared with MSC+TGF-β1 group, the mRNA levels of Acta2 and Col1a1 in MSC+TGF-β1+FSTL1 group were decreased (both P<0.01), and the protein expression levels of collagen Ⅰ and α-SMA were significantly decreased (both P<0.001). Compared with MSC-siNC+TGF-β1 group, the protein level of FSTL1 in cell culture supernatant of MSC-si Fstl1+TGF-β1 group were decreased ( P<0.001), while the protein expression levels of FN and α-SMA were increased (both P<0.001), and the mRNA expression levels of Fn1 and Acta2 were increased (both P<0.05). Conclusions:During unilateral renal IRI-induced renal fibrosis, MSCs in renal interstitium may differentiate into myofibroblasts. FSTL1 may alleviate renal fibrosis after unilateral renal IRI by inhibiting the differentiation of MSCs into myofibroblasts.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Based on the traditional medical theory,the theory of"ear-brain-liver-spleen correlation"was proposed by linking the ear with the brain,liver and spleen.Then,by combining the Chinese medical etiology of Functional Dyspepsia(FD)and the corresponding modern medical mechanism,we realized that the close connection between the ear,brain,liver and spleen is the theoretical basis for treating FD from the ear.In recent years,a new type of vagus nerve stimulation therapy,auricular concha eletro-acupuncture(ACEA),has been developed to treat FD by regulating the liver and spleen through the regulation of the brain,relieving liver depression and strengthening spleen and qi,thus treating FD.In terms of modern medicine,this is related to its ability to reduce anxiety and depression,reduce pain perception,enhance gastrointestinal motility and reduce central and peripheral inflammation by regulating the activity of the corresponding brain functional areas.By exploring the application of auricular concha eletro-acupuncture in FD on the basis of the"ear-brain-liver-spleen correlation",we will better understand the unique role of auricular stimulation in regulating the brain and the blood of the liver and spleen,and promote the inheritance,innovation and development of TCM theory.

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
Humans ; Gene Expression Profiling ; Neoplasms/genetics* ; Organ Specificity ; RNA, Long Noncoding/genetics* ; Transcriptome

Objective:To evaluate the efficacy of T 2* mapping and zoomed imaging with parallel transmission technique (ZOOMit) intravoxel incoherent motion (IVIM) DWI in differentiating benign and malignant thyroid nodules. Methods:The data of 67 patients with thyroid nodules confirmed by surgery and pathology in Ma′anshan People′s Hospital from July 2019 to March 2020 were retrospectively collected. There were a total of 80 nodules, of which 39 were benign nodules and 41 were malignant nodules. All patients underwent MRI including T 2WI, T 2* mapping, and ZOOMit IVIM sequence scans before surgery to measure the T 2*, D, D *, and f values of the nodules. The comparison of the parameters between benign and malignant nodules was evaluated by independent sample t test or Wilcoxon rank sum test. A combined parameter model was established through two-class logistic regression and the predicted probability value was calculated. The ROC curve was used to evaluate the diagnostic efficacy of each parameter and the combined parameter model in differentiating between benign and malignant thyroid nodules. Results:The T 2*, D, f values of benign thyroid nodule group were higher than that in malignant group, and the difference was statistically significant ( P<0.05). The difference of D * value between two groups was not statistically significant ( Z=1.258, P= 0.215). The area under ROC curve (AUC) of T 2*, D, and f values for identifying benign and malignant nodules was 0.703, 0.892, and 0.743, the diagnostic sensitivity was 80.2%, 84.1%, and 80.0%, and the specificity was 65.6%, 81.3%, and 75.0%, respectively. The AUC of T 2*combined with D, T 2*with D * and T 2* with f was 0.925, 0.709, and 0.743, the diagnostic sensitivity was 96.2%, 80.4%, and 80.0%, and the specificity was 81.2%, 65.6%, and 75.0%, respectively. Conclusion:D, f and T 2* derived from ZOOMit IVIM have good value in differentiating between benign and malignant thyroid nodules, and the combination of T 2* and D parameters has the higher diagnostic efficacy.