BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: Rhodiolae Crenulatae Radix et Rhizoma (Hongjingtian in Chinese, RCRR), the roots and rhizomes of Rhodiola crenulata and its application in the medicinal market is very chaotic. In this study, DNA barcoding database and identification engine of Rhodiola species were established, decoction pieces from the medicinal market were identified, and the application and challenges of DNA barcoding in the rapid radiation of Rhodiola species were analyzed. This study provides reference for the protection, rational development, and utilization of endangered resources within Rhodiola species. METHODS: A total of 50 original plant samples from 20 species of the genus Rhodiola from Hebei, Xinjiang, Tibet, Jilin, and other major production areas were collected. Theses samples cover the typical distribution area (Qinghai-Tibetan Platea) of Rhodiola species and other scattered alpine regions (Changbai Mountain, Taibai Mountain, Lushan Mountain, etc.), it encompasses all Rhodiola species with thick rhizomes in China. ITS2 and psbA-trnH barcode of Rhodiola database (BORD) were established and an identification engine named Rhodiola-IDE was developed. The stability and accuracy of the standard DNA barcoding database were evaluated using two datasets. Rhodiola-IDE identified 31 decoction pieces of RCRR from the medicinal material market. RESULTS: The BORD containing 1 532 sequences of 88 Rhodiola species has been established, and the identification efficiency results showed good accuracy and stability. According to the Chinese Pharmacopoeia (2020 edition), 23 samples (74.2%) were identified as authentic R. crenulata, while the rest of the marketed varieties were R. kirilowii, R. dumulosa, and R. fastigiata. The product label "Larger flower, Hongjingtian" was identified as R. crenulata. Samples labeled as "Smaller flower, Hongjingtian" were identified as R. crenulata, R. kirilowii, and R. fastigiata. CONCLUSION ITS2 and psbA-trnH barcodes can identify monophyletic groups represented by R. crenulata. However, for non-monophyletic species, it is necessary to collect as many samples as possible and combine them with multiple markers for joint identification. This study discussed the application and challenges of DNA barcodes in Rhodiola under rapid radiation conditions, providing a scientific basis for the rational development and utilization of Rhodiola varieties.

Objective To explore the efficacy of Yishen Yangyin Gujing Prescription[derived from Zuogui Wan(Bolus for Replenishing Kidney-Yin)]for the treatment of diabetic nephropathy in type 2 diabetes mellitus(T2DM)with qi and yin deficiency syndrome,and to observe its effects on inflammatory responses,pancreatic β-cell function and renal function.Methods A total of 162 T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome who admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2020 to July 2023 were randomly divided into an observation group and a control group according to the random number table method,with 81 cases in each group.The control group was given conventional western medicine treatment for lowering blood pressure and renal protection,while the observation group was treated with Yishen Yangyin Gujing Prescription on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.Before and after the treatment,the changes in the outcomes of the two groups were observed,and the outcomes included the total scores of traditional Chinese medicine(TCM)syndrome,insulin sensitivity index,insulin secretion index,24-h urine total protein quantification(24hUTP),and serum levels of glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),transforming growth factor β1(TGF-β1),NLRP3 inflammasome,interleukin 6(IL-6),superoxide dismutase(SOD)and sphingosine-1-phosphate(S1P).After treatment,the clinical efficacy of the two groups of patients was compared.Results(1)After 12-week treatment,the total effective rate of the observation group was 93.83%(76/81),and that of the control group was 83.95%(68/81).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group(χ2=9.163,P<0.05).(2)After treatment,the insulin sensitivity index and insulin secretion index in the two groups of patients were increased(P<0.05)and the total scores of TCM syndromes were decreased(P<0.05)when compared with those before treatment,and the increase of insulin sensitivity index and insulin secretion index as well as the decrease of the total scores of TCM syndrome in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the serum levels of HbA1c,FINS,FBG,SCr,BUN and 24hUTP in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum TGF-β1,IL-6,and NLRP3 inflammasome levels in the two groups of patients were decreased(P<0.05)and the serum S1P and SOD levels were increased(P<0.05)when compared with those before treatment,and the decrease of serum TGF-β1,IL-6,and NLRP3 inflammasome levels as well as the increase of serum S1P and SOD levels in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome,the combined use of western medicine and Yishen Yangyin Gujing Prescription treatment is helpful to alleviate inflammatory response,improve the function of pancreatic β-cells,regulate the blood glucose level,improve renal function,and enhance the clinical efficacy.

Objective To investigate the effect of different strand lengths of 125I seeds with the same activity on the dose of different reference points around the seeds.Methods The scanned images were transferred to the three-dimensional treatment planning system(3D-TPS)according to DICOM format.The target volume was delineated at 5 mm and 10 mm above and below the center of the phantom,and a 0.8 mCi seeds strand was simulated.The 1-20 seeds were arranged with an equal spacing of 5 mm(5 mm-100 mm).The 5 mm points above and below the center of the seeds strand were defined as point A and point A',and the 10 mm points above and below the center were defined as point B and point B'.5 mm above and below the edge of the seeds strand on the left side were defined as AL points and AL'points,and 5 mm above and below the edge of the seeds strand on the right side were defined as AR points and AR'points.Similarly,points 10 mm above the above mentioned positions were defined as BL points,BL'points,BR points,BR'points.The average dose symmetry points were measured at AL,AL',AR,and 5 mm,10 mm,15 mm and 20 mm inside AR' of the 45 mm-100 mm seeds strand.The dose at the center was compared with the dose at the end points.The dose at the center point A was compared with the average dose at the symmetry points of 5 mm,10 mm,15 mm and 20 mm inside of the end points AL,AL',AR and AR',and the dose at each point was curve fitting.The correlation between each point and seeds strands of different lengths was analyzed.Results There was a positive correlation between the dose and the length of each point.There was no statistically significant difference between the center point and the end point.There was a statistically significant difference in dosage at points 5 mm and 10 mm inside from point A,while there was no statistically significant difference in dosage at points 15 mm and 20 mm inside from point A.The dose of A,A',B and B' point increased steadily with the increase of seed chain length,and the fitting curves were obtained respectively:y=e(-0.620/x+5.28)(R2=0.992),y=e(-0.640/x+5.34)(R2=0.987),y=e(-0.82/x+4.80)(R2=0.984),y=e(-0.82/x+4.83)(R2=0.9g1).Conclusion The doses at points A,A',B,and B'are positively correlated with seeds strand length and have a high degree of stability.Point A can be used as a reference point for the target area dose of the seeds strand,and point B can be used as a reference point for the dose to critical organs.The dose at other positions is more variable and thus has a certain degree of uncertainty as a reference point for the seeds strand dose.

Objective To investigate the relationship between the absorbed dose and implantation duration at the target area and at the critical organ dose reference points in the application of radioactive 125I seed strands for the treatment of intraluminal tumors.Methods A self-developed 125I seed strand arc template with a 30-degree angle was used to place 10 seeds(each with activity of 1.0mCi)into the template.CT-based DICOM images were transferred to a treatment planning system(TPS)for dose calculation.Absorbed doses at multiple time points(from day 5 to day 90 with a 5-day interval)were measured at following four specific locations:point A'(5 mm inside the arc center),point A(5 mm outside the arc center),point B(10 mm outside the arc center),and point B'(10 mm inside the arc center).The TPS was first used to calculate the expected absorbed doses,followed by actual absorbed dose measurements over the 90-day period.The expected absorbed doses were calculated,and then the actual absorbed doses were calculated.The time-dose relationship of the above points was analyzed,and the curves and equations were obtained.Results The expected absorbed doses at points A',A,B,and B'were 221.36,196.39,115.78,and 136.32 Gy,respectively.The time(x)-dose(y)relationships of all the above points followed a quadratic function relationship in the form of y=c+bx-ax2.Within the time range of 5-90 days,the actual absorbed dose increased with the prolongation of time,and the increase speed showed a pattern of first fast and then slow.The increase in speed was fast within 20 days,than became stable between 20-75 days,and after 75 days the increase in speed became to slow down.Conclusion When using 125I seed strands to treat intraluminal tumors,the actual absorbed dose of the tumor needs to be accurately calculated based on the implantation duration.The actual absorbed dose initially accumulates rapidly and decreases significantly after 75 days.It is recommended to replace the 125I seed strand with a new one after implanting it for approximately 75 days.

Objective To investigate the impact of different 125I seeds strand radian on the dose of different reference points around the seeds.Methods CT scan of self-developed radioactive particle radiation dose measurement phantom was performed,the scanned images were transferred to the three-dimensional treatment planning system(TPS).The target area at the middle level of the model was drawn.The target volume was delineated at 5 mm and 10 mm above and below the center of the phantom.125I seeds strand plans were designed with different radians,with a total length of 8 cm,seed spacing of 0 cm,activity of 0.8 mCi,and a total of 16 particles,with radians ranging from 30°to 170°,increasing by 10° increment.The point 5 mm vertically away from the center of the seeds strand towards the center was named A',and the point away from the center was named A.The point 10 mm vertically away from the center of the seeds strand towards the center was named B',and the point away from the center was named B.The doses at different radians were recorded,and the actual absorbed dose at 1-2 months after operation was calculated based on the particle activity decay formula.Results The doses at points A'and A were(218.3±23.1)and(201.5±16.0)Gy respectively(P=0.001).The actual absorbed doses at 1 month after operation were(65.5±6.9)and(60.5±4.8)Gy respectively(P=0.001),and the actual absorbed doses at 2 months after operation were(109.2±11.5)Gy and(100±7.9)Gy respectively(P=0.001).The doses at points B'and B were(95.9±11.0)Gy and(81.7±4.9)Gy respectively(P＜0.001),and the actual absorbed doses at 1 month after operation were(28.8±3.3)Gy and(24.5±1.5)Gy respectively(P＜0.001).The actual absorbed doses at 2 month after operation were(48.0±5.5)Gy and(41.0±2.4)Gy respectively(P＜0.001).The doses at points A'and A gradually decreased with the increase of the radians,reaching the minimum value at 100 degrees,and then increased gradually,showing a cubic function change.The actual absorbed dose showed the same trend.The doses at points B'and B increased gradually with the increase of the radians,showing a cubic function change.Conclusion At different radians,the point doses and absorbed doses on the centrifugal side of the seeds strand are both less than those on the centripetal side.There is a cubic function relationship between the dose at the reference points and the radian of the seeds strand.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL^-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d^-1）， and low- and high-dose （crude drug 3.4， 17 g·kg^-1·d^-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL^-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.

Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.

Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ²＝46.077，P＜0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m² (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.