Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Osteoporosis(OP) is a metabolic bone disorder characterized by reduced bone mass and degenerative bone tissue. Osteoporotic pain(OPP) is its most common clinical symptom, significantly affecting the quality of life of patients. With the limitations of modern medical treatments and the intensification of aging, it is imperative to explore more cost-effective interventions for OPP. This paper, based on databases such as China National Knowledge Infrastructure(CNKI), VIP, Wanfang, BioMed, and Web of Science, uncovered the connection between the pathogenesis of OPP in traditional Chinese medicine(TCM) and modern medical mechanisms and retrospectively summarized the basic and clinical research methods and evidence of TCM prescriptions in the treatment of OP and related pain diseases. Studies have shown that TCM prescriptions, focusing on treatments such as nourishing the kidney, strengthening the spleen, and activating blood circulation to remove blood stasis, can significantly improve pain symptoms, increase bone mineral density(BMD), and adjust bone metabolic indicators such as C-terminal telopeptide of type Ⅰ collagen(CTX), serum bone Gla-protein(S-BGP), and alkaline phosphatase(ALP). The mechanisms of action of TCM prescriptions in treating OP and improving OPP symptoms were related to signaling pathways such as Wnt/β-catenin, nuclear factor kappa-B(NF-κB), mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and the osteoprotegerin(OPG)/receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand(RANKL) axis. Further strengthening the accumulation and analysis of clinical data, rigorously designing and conducting randomized controlled trials of TCM treatments for OPP with large sample sizes, standardizing outcome measures in basic and clinical research by using methods such as the core outcome set(COS), and incorporating mass spectrometry and omics approaches to uncover more potential active components and mechanisms may contribute to a deeper exploration of the advantages and essence of TCM prescriptions in the treatment of OPP.
Humans ; Osteoporosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Retrospective Studies ; Bone Density/drug effects* ; Medicine, Chinese Traditional ; Pain/metabolism* ; Animals

OBJECTIVE: To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO). METHODS: Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement). RESULTS: All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L^-1 and (204.47±35.59) μg·L^-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L^-1 and (311.12±42.23) μg·L^-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s^-1, (0.57±0.15) m, and (0.99±0.11) m·s^-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s^-1, (0.50±0.14) m, and (0.95±0.09) m·s^-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05). CONCLUSION The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Tibia/physiopathology* ; Aged ; Biomechanical Phenomena ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology*

Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To systematically evaluate the efficacy and safety of Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.Methods Wanfang database,CNKI,VIP,SinoMed,Cochrane Library,PubMed,Embase and Web of Science databases were searched to collect randomized controlled trials(RCTs)of Compound Danshen dripping pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.The retrieval time is from the establishment of the database to May 2023.Two researchers independently completed literature screening,data collation and risk of bias evaluation.RevMan 5.4 software was used for Meta-analysis.Results Twenty-four RCTs with a total of 2 546 patients were included.Meta-analysis showed that the treatment of Compound Danshen Dripping Pills combined with conventional western medicine was better than that of conventional western medicine in improving the total effective rate of coronary heart disease complicated with diabetes mellitus[OR=4.93,95%CI(3.49,6.98),P＜0.000 01],plasma adiponectin[MD= 2.79,95%CI(2.30,3.27),P＜0.000 01],reducing fasting blood glucose[SMD=-1.06,95%CI(-1.24,-0.88),P＜0.000 01],postprandial two-hour blood glucose[MD=-1.53,95%CI(-1.71,-1.35),P＜0.000 01],glycosylated hemoglobin[MD=-1.56,95%CI(-2.01,-1.11),P＜0.000 01],homocysteine[MD=-8.47,95%CI(-8.89,-7.97),P＜0.000 01],low density lipoprotein[MD=-0.46,95%CI(-0.69,-0.24),P＜0.000 01],total cholesterol[MD=-0.45,95%CI(-1.11,-0.20),P=0.005],triglycerides[MD=-0.42,95%CI(-0.50,-0.34),P＜0.000 01],interleukin 6[SMD=-1.34,95%CI(-1.61,-1.07),P＜0.000 01],cardiovascular adverse events[OR=0.35,95%CI(0.19,0.64),P=0.000 6],incidence of adverse reactions[OR=0.45,95%CI(0.24,0.86),P=0.01].Conclusion Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease with diabetes mellitus is more effective than conventional western medicine treatment,and with better safety.However,due to the limit of the quality of the included studies and other factors,the above conclusions still need to be verified by more high-quality clinical trials.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

Humans ; Leg/pathology* ; Skin Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*

ObjectiveTo study the inhibitory effect of Banxia Houputang （BHT） on lipopolysaccharide （LPS）-induced inflammation of microglia （BV2） cells and the neuroprotective effect on human neuroblastoma （SH-SY5Y） cells. MethodAfter the neuroinflammatory model was constructed by LPS inducing BV2 cells， model group （LPS 100 µg·L^-1）， administration groups （LPS+1 g·L^-1 BHT， LPS+2 g·L^-1 BHT， LPS+5 g·L^-1 BHT， LPS+10 g·L^-1 BHT）， and blank group were given DEME medium at the same volume. In addition， neuronal apoptosis model was established by co-culture of LPS-induced BV2 cell inflammation medium and SH-SY5Y cells （LPS-DMEM） and was administrated according to the above grouping. Cell viability was detected by Cell Counting Kit-8 （CCK-8） assay. The content of nitric oxide （NO） and that of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by Griess aasay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA levels of TNF-α， IL-1β， interleukin-4 （IL-4）， nitric oxide synthase （iNOS）， and interleukin-10 （IL-10） were measured by real-time polymerase chain reaction （Real-rime PCR）. Western blot was used to detect the expression levels of signal transducer and activator of transcription 3 （STAT3）， Janus kinase 2 （JAK2） and nuclear factor kappa-B （NF-κB p65）， protein kinase B （Akt）， inhibitor of nuclear factor κB α （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax）. ResultCompared with blank group， LPS increased the NO release， levels of TNF-α， IL-1β， IL-6， and iNOS and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3， decreased the content of IL-4 and IL-10 in BV2 cells， and induced apoptosis of co-cultured SH-SY5Y cells （P<0.01）. Compared with model group， BHT reduced the content of NO， TNF-α， IL-1β， and iNOS （P<0.01） and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3 （P<0.01）， elevated the content of IL-4 and IL-10 （P<0.01）， and inhibited the apoptosis of SH-SY5Y cells induced by LPS-DMEM （P<0.01）. ConclusionThis experiment reveals that BHT inhibited LPS-induced inflammation in BV2 cells by regulating Akt/NF-κB/JAK2/STAT3 signaling pathway and showed neuroprotective effects on SH-SY5Y cells.