OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Objective:To evaluate the effect of different doses of compound sodium chloride injection combined with norepinephrine on prevention of hypotension after lumbar anesthesia in the patients undergoing caesarean section.Methods:A total of 150 patients with a singleton fetus, aged 18-45 yr, at ≥37 weeks of gestation, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with height ≥150 cm, weighing ≤100 kg, with body mass index < 40 kg/m 2, scheduled for elective caesarean section under lumbar anesthesia, were divided into 3 groups ( n=50 each) by the random number table method: compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 groups (group A, group B, group C). Compound sodium chloride injection 4 ml/kg was intravenously injected for liquid preload before lumbar anesthesia, and 0.5% hyperbaric bupivacaine 12.5 mg was injected to the subarachnoid space for lumbar anesthesia. Norepinephrine was intravenously injected at a dose of 6 μg immediately after intrathecal injection, followed by an infusion of 0.05 μg·kg -1·min -1, and infusion was stopped at 5 min after delivery. Compound sodium chloride injection was intravenously infused simultaneously at a rate of 4, 8 and 12 ml·kg -1·h -1 in A, B and C groups, respectively. The maximum diameter of inferior vena cava (IVCmax) and the minimum diameter of inferior vena cava (IVCmin) were measured by ultrasound, and inferior vena cava collapse index (IVC-CI) was calculated at 1 min before fluid preload (T 1), immediately after fluid preload (T 2), at 5 min after anesthesia (T 3), at 5 min after fetal delivery (T 4) and immediately before leaving the operating room (T 5). The incidence of intraoperative adverse events (hypotension, severe hypotension, bradycardia, hypertension, nausea, and vomiting) and neonatal outcomes (umbilical artery blood gas index and Apgar score at 1 and 5 min after birth) were recorded. Results:Compared with group A, IVCmin was significantly increased and IVC-CI was decreased at T 5 in group B, and IVCmin and IVCmax were significantly increased and IVC-CI was decreased at T 5 in group C ( P<0.05). There was no significant difference in IVCmax, IVCmin and IVC-CI at each time point between group B and group C ( P>0.05). There was no significant difference in the incidence of hypotension, severe hypotension, bradycardia, hypertension, nausea and vomiting among the three groups ( P>0.05). There was no significant difference in the results of blood gas analysis of the umbilical artery and Apgar score at each time point after birth among the three groups ( P>0.05). Conclusions:Compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 combined with norepinephrine can effectively prevent the occurrence of hypotension after lumbar anesthesia in the patients undergoing caesarean section without increasing maternal and infant adverse events, and the effect of 8 and 12 ml·kg -1·h -1 for volume supplementation is better than that of 4 ml·kg -1·h -1.

A UPLC-Q-Orbitrap-MS based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the intervention effects of Suanzaoren Decoction (SZRD) on chronic unpredictable mild stress (CUMS) depression rats, and to clarify the metabolic regulation pathway of SZRD. The rats were randomly divided into normal control group, CUMS model group, positive drug venlafaxine group, SZRD high (24 g·kg^-1) and low (12 g·kg^-1) dose groups, respectively. The CUMS model was replicated by subjecting to a variety of stimulus, such as thermal stimulation, ice water swimming, ultrasonic stimulation, tail clamping, day and night reversal, plantar electric shock and so on for rats. After oral administration of drugs for 28 days, the behavioral indexes of rats in each group were observed and the hippocampus and serum samples of rats were collected for biochemical assay and histopathological inspection. Compared with the CUMS model group, low dose and high dose SZRD groups can significantly reduce the immobility time of forced swimming (P < 0.001, P < 0.001), increase the sucrose preference rate (P < 0.01, P < 0.05), the number of crossings (P < 0.05, P < 0.01) and the number of uprights (P < 0.05, P < 0.01) in the open field test, suggesting that SZRD can significantly improve the depression-like behavior of CUMS model rats. In addition, SZRD could significantly reduce the levels of serum IL-6, IL-1β and TNF-α of CUMS model rats. A total of 21 differential metabolites in serum were identified by comparison with the data from the literature and databases. In addition, low-dose SZRD and high-dose SZRD improved the 8 and 11 perturbed potential serum biomarkers that were induced by CUMS, respectively, which related to alanine, aspartic acid and glutamic acid, tryptophan and arachidonic acid metabolism. This study provides a scientific basis for expanding the clinical indications of SZRD. This experiment was approved by the Animal Ethics Committee of Shanxi University (Approval No. SXULL2020028).

ObjectiveTo construct ¹³¹Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed， and ¹³¹Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy， and the radioactive uptake ratio of ¹³¹Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of ¹³¹Ⅰ-NT was obtained through injecting ¹³¹Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of ¹³¹Ⅰ-NT was （93.05±0.74） %， and the radiochemical purity post purification was （98.35±0.32） %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was （92.77±0.04） % and （89.43±0.2） %， respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after ¹³¹Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of ¹³¹Ⅰ-NT through tail vein， the radioactive uptake per gram of tumor tissue were （4.9±0.55）%ID/g， （10.12±0.32）%ID/g and （4.25±0.31）%ID/g at 30 min， 1 h and 2 h， respectively. The T/M ratio was 7.33±2.04， 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe ¹³¹Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully， which possesses relatively high stability in vitro ， and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that ¹³¹Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer， which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
Humans ; Carcinoma, Renal Cell/pathology* ; Cell Proliferation ; Hypoxia ; Kidney Neoplasms ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; RNA, Circular/metabolism* ; RNA, Small Interfering ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O₂) or hypoxia condition (1%O₂). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×10⁶/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×10⁶/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD₃₁], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD₃₁ showed that, the expressions of VEGFA and CD₃₁ in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD₃₁ in BMSC-exo group and CD₃₁ in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD₃₁ in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.
Rats ; Female ; Humans ; Animals ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism* ; Vascular Endothelial Growth Factor A ; Exosomes/metabolism* ; Uterine Diseases/therapy* ; Collagen ; Hypoxia/therapy* ; Fibrosis ; Mesenchymal Stem Cells/metabolism* ; Oxygen

[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

In the past few years, continuous manufacturing(CM) has been put forward by the FDA. Pharmaceutical enterprises are encouraged to promote the implementation of CM, which has become a hot research direction of pharmaceutical technology. In February 2019, the FDA issued a draft guideline for the implementation of CM, which greatly promoted the development of CM and provided reference for continuous manufacturing of traditional Chinese medicine(TCM). The production process of TCM is a complex system. With the innovation of production equipment and the promotion of automation and informatization of TCM production, the exis-ting policies, regulations and traditional production control capacity are difficult to meet the market demand for high-quality TCM pro-ducts. In this paper, we reviewed the new technologies and methods of quality control in accordance with the characteristics of TCM production by referring to modern manufacturing technology, information technology and quality control technology. Based on the "QbD" theory and "PAT" technology, process knowledge system(PKS), an advanced control strategy, was proposed to provide a reference for the implementation of CM in TCM production.
Commerce ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Technology, Pharmaceutical