This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Purpose::This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects.Methods::Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. Results::In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment.Conclusion::Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

This review introduced the research progress of covalent modification strategies in local anesthetic drug delivery systems. As a commonly used and multimodal analgesic drug, local anesthetics have limited duration of action and potential toxicity in clinical application. In order to prolong the analgesic effect and reduce systemic toxicity, researchers are committed to the development of sustained-release local anesthetics with long-lasting dose-controlled-release functions. When it comes to the delivery of local anesthetics, the covalent modification strategy is a key approach. By covalently binding drugs to large molecule carriers, covalent modification strategies can improve drug stability, targeting and delivery efficiency. Macromolecular prodrugs can modulate the kinetic process of the drug, so that the drug is released in the form of the active ingredient and achieve better therapeutic effects. In recent years, stimulus-responsive macromolecular prodrugs have become a research hotpot for local anesthetic drug delivery systems, and the stimulus-responsive performance of macromolecular prodrugs can rapidly release drugs under internal and external stimulus conditions, and maintain low toxicity and high efficiency in blood circulation and normal tissues. These emerging research directions provide important guidance for prolonging the analgesic effect of local anesthetics and reducing systemic toxicity, and provide new idea for the development of more effective drug delivery systems in the future.

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.
Transcription Factors/metabolism* ; Lonicera/metabolism* ; Phylogeny ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.
Humans ; Medicine, Chinese Traditional ; Syndrome ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy* ; China

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Syndrome ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Prescriptions

Hypertension and its target organ damage have become a major public health problem. Sexual dysfunction is a new problem in the treatment of modern hypertension. Modern pathophysiological studies have shown that hypertension can lead to sexual dysfunction. In addition, three major hypotensive drugs represented by diuretics can also lead to sexual dysfunction. In traditional Chinese medicine(TCM), hypertension belongs to "vertigo" "headache" "head wind", etc. In the past, the understanding of the TCM pathogenesis of hypertension was mainly from the perspectives of "liver wind" and "Yang hyperactivity". However, based on the in-depth research on ancient and modern literature and medical records and many years of clinical practice, it has been identified that kidney deficiency was the key pathogenesis. Hypertension complicated with sexual dysfunction belongs to the category of kidney deficiency syndrome in TCM, especially the deficiency of kidney Yin. Previous studies by other research groups showed that Yin-enriching and kidney-tonifying method could effectively reduce blood pressure, improve sexual dysfunction, reverse risk factors, and protect target organs. This article systematically discussed the TCM understanding, modern pathophysiological mechanism, and the clinical treatment strategy of kidney-tonifying drugs(single drugs and compounds) in the treatment of hypertension complicated with sexual dysfunction in order to provide a scientific basis for kidney-tonifying method in the treatment of hypertension complicated with sexual dysfunction.
Humans ; Antihypertensive Agents/therapeutic use* ; Medicine, Chinese Traditional ; Hypertension/drug therapy* ; Blood Pressure ; Risk Factors ; Drugs, Chinese Herbal/therapeutic use*

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
Animals ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species ; Tumor Suppressor Protein p53/genetics* ; Signal Transduction ; Liver ; Aging ; Cell Cycle Proteins ; Interleukin-6

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.