ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

OBJECTIVES: To explore the mechanism of Qingda Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs). METHODS: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks. The control rats, along with 6 age-matched WKY rats, were treated with saline only. Blood pressure changes of the rats were monitored, and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining. Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR, and the protein expressions of NeuN, STAT3, Bcl-2, Bax, and cleaved caspase-3 were detected with immunohistochemistry and Western blotting. In a HT22 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis, expressions of miR-124 and STAT3 mRNA, and protein expressions of STAT3, Bcl-2, Bax, and cleaved caspase-3 were evaluated using CCK8 assay, Hoechst 33342 staining, RT-qPCR, and Western blotting. RESULTS: Compared with WKY rats, SHRs had significantly elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex, reduced expressions of NeuN, miR-124 and Bcl-2, and enhanced expressions of STAT3, Bax and cleaved caspase-3 (P<0.05). All these changes in the SHRs were significantly ameliorated by treatment with QDG (P<0.05). In the HT22 cell model, QDG treatment obviously reduced OGD/R-induced cell apoptosis, increased the expressions of miR-124 and Bcl-2, and suppressed the elevation of protein expressions of STAT3, Bax and cleaved caspase-3. CONCLUSIONS QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.
Animals ; Rats, Inbred SHR ; MicroRNAs/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Apoptosis/drug effects* ; Rats, Inbred WKY ; Male ; Hypertension

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Objective:To investigate the correlation between serum ischemia modified albumin (IMA) and calmodulin (CaM) expression levels and neurological impairment in patients with cerebral small vessel disease.Methods:The clinical data of 140 patients with cerebral small vessel disease (CSVD) who received treatment at The Third People Hospital in Liaocheng between April 2020 and December 2021 were retrospectively analyzed. On admission, serum levels of CaM and IMA were measured using an enzyme-linked immunosorbent assay and an albumin-cobalt binding test. Patients' neurological function was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients' transient cerebral ischemia, urinary incontinence, and gait disturbance were evaluated using the National Institute of Neurological Disorders and Stroke Scale. Patients' cognitive function was evaluated using the Montreal Cognitive Assessment scale. The influential factors of serum IMA and CaM expression levels in patients with CSVD were analyzed. The factors that affect the severity of neuological imairment in patients with CSVD and their correlation with serum IMA and CaM expression levels were analyzed.Results:The gender, age, presence or absence of gait disorders, and presence or absence of urinary incontinence of patients were not correlated with serum IMA and CaM levels (all P > 0.05). The serum levels of IMA [(38.5 ± 5.3) × 103U/L, (38.5 ± 4.7) × 103U/L, (39.0 ± 4.4) × 103U/L] and CaM [(190.4 ± 34.5) μg/L, (191.2 ± 26.7) μg/L, (199.7 ± 24.8) μg/L] in patients with cognitive impairment, dizziness and vertigo, and transient cerebral ischemia were significantly higher than those in patients with normal cognitive function, patients without dizziness and vertigo, or patients without transient cerebral ischemia [(27.3 ± 4.4) × 103U/L, (21.0 ± 3.8) × 103U/L, (20.5 ± 5.1) × 103U/L, (180.6 ± 29.6) μg/L, (179.5 ± 28.6) μg/L, (168.6 ± 32.4) μg/L, t = 14.10, 24.36, 22.50, all P < 0.05]. There were significant differences in cognitive impairment (38/16/9), dizziness and vertigo (39/16/8), transient cerebral hemorrhage (35/16/9), NIHSS score [(3.6 ± 0.8) points, (7.5 ± 0.9) points, (16.2 ± 3.2) points], CaM levels [(125.3 ± 20.5) μg/L, (185.5 ± 23.6) μg/L, (237.9 ± 54.3) μg/L], and IMA levels [(21.2 ± 3.5)] × 103 U/L, [(38.5 ± 4.3) × 103 U/L, (74.9 ± 5.4) × 103 U/L] among patients with mild, moderate, and severe neurological impairment ( t = 32.87, 11.28, 12.42, 34.59, 151.73, 147.84, all P < 0.05). The results of multivariate analysis indicated that cognitive impairment ( OR = 1.578, 95% CI: 1.043-2.386), transient cerebral ischemia ( OR = 2.396, 95% CI: 1.156-4.969), dizziness and vertigo ( OR = 1.906, 95% CI: 1.086-3.345), NIHSS score ( OR = 2.171, 95% CI: 1.162-4.056), CaM level ( OR = 2.022, 95% CI: 1.268-3.224), and increased IMA levels ( OR = 2.090, 95% CI: 1.313-3.325) were independent influential factors for worsened neurological impairment (all P < 0.05). The serum levels of IMA and CaM in patients with CSVD were significantly positively correlated with the severity of neurological impairment ( r = 5.45, 8.33, both P < 0.05). Conclusion:The elevated serum levels of IMA and CaM in patients with CSVD serve as independent risk factors for neurological impairment, and these levels are positively correlated with the severity of neurological impairment.

Objective To explore the coronary flow reserve(CFR)in patients with coronary slow flow(CSF)and the diagnostic value of non-invasive myocardial work indices derived from echocardiography for CSF.Methods A retrospective study was conducted on 65 patients who underwent coronary angiography at the Zhongshan Hospital(Xiamen Branch),Fudan University due to angina pectoris,coronary artery risk factors,or electrocardiographic abnormalities from August 2020 to November 2023.Patients were divided into two groups based on the corrected TIMI frame count(cTFC):the CSF group(n=35)and the normal coronary blood flow velocity group(control group,n=30).Both groups underwent an adenosine triphosphate(ATP)drug load test to measure their coronary flow reserve(CFR).Conventional indices and myocardial work indices via echocardiography and two-dimensional speckle-tracking imaging(2D-STI)were acquired:left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),E/e'ratio,global longitudinal strain(GLS),global constructive work(GCW),global wasted work(GWW),global work index(GWI),and global work efficiency(GWE).Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic value of myocardial work indices for CSF.Results There was no significant difference in CFR values between the two groups,but the proportion of CSF group with CFR less than 2 was higher than that of the control group(P=0.023).Compared with the control group,the CSF group showed significantly lower levels of GLS,GWI,and GCW(P＜0.05).ROC curve analysis revealed that the GLS diagnostic threshold for CSF was-19.5%,with a sensitivity of 64.7%,specificity of 78.6%,and AUC of 0.793.Among the myocardial work indices,the AUC of GWI was the highest(0.825),with a sensitivity of 88.2% and specificity of 75.0% .Conclusions Some CSF patients retain coronary microcirculatory blood flow reserve function,but the proportion of patients with reduced CFR function is increasing.The left ventricular myocardial work indices can identify early myocardial work abnormalities and monitor myocardial ischemic damage in CSF patients.

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

Objective:To study the correlation of bone metabolism biomarkers between newborn twins and their mothers during pregnancy.Methods:From January 1, 2018 to June 30, 2022, newborn twins with mild symptoms admitted to the neonatal department of our hospital were retrospectively reviewed. The clinical data of the twins and their mothers were collected, including bone metabolism biomarkers of the twins within 3 d after birth and their mothers within last month during pregnancy. The twins were assigned into different groups according to gestational age(GA), birth weight(BW), the relationship between BW and GA(appropriate for GA(AGA),small for GA(SGA) and large for GA(LGA), birth season, gender, and the mothers' age, ethnicity, pre-delivery body mass index (BMI), gestational BMI increase, number of births and chorionic properties. The correlations of bone metabolism biomarkers between the twins and their mothers were analyzed.Results:A total of 302 pairs of twins were included. The incidence of insufficient or deficient serum 25-(OH)D 3 was 97.4% among the mothers, and 87.7% among the twins. The levels of blood phosphorus ( r=0.262, P<0.001) and 25-(OH)D 3 ( r=0.239, P=0.002) in mothers were positively correlated with the twin with larger BW. No significant differences existed in 25-(OH)D 3 between genders, AGA,SGA and LGA, birth season, and mothers' age, ethnicity, pre-delivery BMI, gestational BMI increase and chorionic properties( P>0.05). 25-(OH)D 3 in the twins were positively correlated with BW and 25-(OH)D 3 of mothers before delivery ( P<0.05) and negatively correlated with number of births ( P<0.05). Conclusions:In most mothers and their newborn twins, 25-(OH)D 3 are insufficient or deficient. The levels of blood phosphorus and 25-(OH) D 3 are correlated between the newborns and their mothers. The lower the BW of the newborn, the more times the mother give birth and the lower the mother's pre-delivery 25-(OH)D 3 level, the lower the newborn's 25-(OH)D 3 level.

Objective:To explore the safety and efficacy of 20% glucose solution in the treatment of adult diabetic patients with hypoglycemia.Methods:A non-randomized controlled paired design trial was conducted. The diabetes patients with hypoglycemia (blood glucose < 3.9 mmol/L) who were admitted to the department of endocrinology and metabolism of Affiliated Hospital of Jiangsu University from December 2020 to May 2021 were enrolled. When the patients developed hypoglycemia for the first time, 75 mL of 20% glucose solution was pumped intravenously at a constant speed within 15 minutes, which was named the 20% glucose solution group. When the patients had hypoglycemia again, 30 mL of 50% glucose solution was pumped intravenously at a constant speed within 3 minutes, which was named the 50% glucose solution group. If the blood glucose was still ≤ 3.9 mmol/L at 15 minutes of hypoglycemia treatment, or the patients were uncomfortable due to too fast drip speed, it should be terminated immediately. The hypoglycemia treatment should be handled according to the Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition). The peripheral blood glucose level and the range of increase at 15 minutes of treatment, the success rate of one treatment, the peripheral blood glucose values at 60 minutes after successful hypoglycemia treatment, the incidence of phlebitis and exudation after hypoglycemia treatment, and the pain of local blood vessels in patients with hypoglycemia treatment were analyzed and compared between the two groups. Results:A total of 65 patients completed the treatment of hypoglycemia with 20% glucose solution and the success rate of one treatment was 100%. The peripheral blood glucose value at 15 minutes of hypoglycemia treatment was (8.30±1.37) mmol/L, and the increased range was (4.86±1.30) mmol/L. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment was (6.96±1.48) mmol/L, which indicated that 20% glucose solution could effectively increase blood glucose. Among 65 patients, 32 patients had hypoglycemia again, who were treated with 50% glucose solution, and the success rate of one treatment was 100%. When patients who received 50% glucose solution for hypoglycemia formed a paired design with the first 20% glucose solution treatment, the results showed that there was no significant difference in the peripheral blood glucose value and the increased range in blood glucose at 15 minutes of hypoglycemia treatment between the 20% glucose solution and the 50% glucose solution groups [peripheral blood glucose (mmol/L): 8.20 (7.70, 9.70) vs. 8.30 (7.80, 8.80), increase in blood glucose (mmol/L): 4.96±1.39 vs. 4.70±1.32, both P > 0.05], indicating that the glucose changing at 15 minutes of hypoglycemia treatment with 20% glucose solution was similar to that with 50% glucose solution. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment of 20% glucose solution group was significantly lower than that of 50% glucose solution group (mmol/L: 6.37±1.04 vs. 7.20±1.36, P < 0.01), which meant that the blood glucose tended to be more stable. There was no phlebitis and exudation after hypoglycemia treatment in both groups. The pain score of 20% glucose solution group was 0, however, 3 patients in 50% glucose solution group complained of local vascular pain, and the pain score was 1. Conclusions:20% glucose solution can effectively treat hypoglycemia in diabetic patients, which has the same curative effect as 50% glucose solution and much safer. It can be used in patients with severe hypoglycemia.

Objective　To analyze the relationship between single nucleotide polymorphism （SNP） of microRNA-146a （miR-146a） gene and Parkinson’s disease （PD）. Methods　In a case-control study，446 patients （PD group） with primary PD were selected from our hospital from October 2015 to August 2019，and 450 healthy people in the health examination center of the same period were selected as the control group，the SNP of rs2910146 and rs5709329 loci in miR-146a were detected by DNA PCR sequencing technology；and the risk factors of PD were analyzed by logistic regression. Results　The genotypes of rs2910146 and rs5709329 in miR-146a in PD group and control group were consistent with Hardy-Weinberg equilibrium law （P>0.05）. There was no significant difference in gender，age，BMI and education between PD group and control group （P>0.05）. Compared with the control group，the G allele and GG genotype frequency of rs2910146 locus in PD group were significantly lower （P<0.05）. There was no significant difference in allele frequency and genotype distribution of rs5709329 locus between PD group and control group （P>0.05）. SNP at rs2910146 in miR-146a was related to cognitive dysfunction and age of PD patients （P<0.05），but not to gender，PD subtype and first-onset limb （P>0.05）. Carrying GG genotype was an independent protective factor for PD （P<0.05）.Conclusion　SNP at rs2910146 locus in miR-146a is related to age and cognitive impairment in PD patients，and carrying GG genotype may reduce the risk of PD.

Objective To explore the effects of early activity on preventing acquired weakness in Cardiovascular Critical Surgery patients. MethodsFrom May 2018 to May 2019, we selected 140 patients of Cardiovascular Critical Surgery at Zhengzhou Seventh People's Hospital as subjects by convenient sampling. All of patients were divided into observation group and control group with the method of random number table, 70 cases in each group. Control group implemented routine nursing. On the basis of that in control group, observation group carried out early activity. We compared the incidence of acquired weakness, time of mechanical ventilation, hospital stay, time to get out of bed, the scores of Medical Research Council (MRC) when leaving Cardiovascular Critical Surgery, the Fugl-Meyer measurement for motor function and activities of daily living (ADL) one month after discharge of patients between two groups. ResultsThe incidence of acquired weakness of observation group was 7.1%(5/70) lower than that (20.0%,14/70) of control group with a statistical difference (P＜0.05). The time of mechanical ventilation, hospital stay, time to get out of bed in observation group were shorter than those in control group with statistical differences (P＜ 0.05). After intervention, the scores of MRC when leaving Cardiovascular Critical Surgery, the Fugl-Meyer measurement for motor function and ADL one month after discharge in observation group were higher than those in control group with statistical differences (P＜ 0.05). ConclusionsEarly activity can effectively decrease the acquired weakness in Cardiovascular Critical Surgery patients, shorten the hospital stay, improve patients' motor function and ADL, which is worthy of clinic application.