Mechanism of Youguiwan Regulating BMP-2/Smad Signaling Pathway to Promote Bone Formation in Postmenopausal Rats with Osteoporosis / 中国实验方剂学杂志

ObjectiveTo observe the effects of Youguiwan on bone metabolism and bone morphogenetic protein-2 （BMP-2）/Smad signaling pathway in ovaries-removed rats with osteoporosis and study the mechanism of Youguiwan in the prevention and treatment of osteoporosis. MethodA postmenopausal rat model of osteoporosis was prepared by bilateral ovariectomy. The 40 female SD rats were randomly divided into five groups， including sham operation group， model group， alendronate sodium group （0.1 mg·kg-1）， and high-dose and low-dose （5.36 and 2.68 g·kg-1） groups of Youguiwan. The drug was given seven days after modeling， once a day for 12 weeks. After the treatment， the changes in femur tissue structure were observed by micro-CT， including bone mineral density （BMD）， bone volume/total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone surface/bone volume （BS/BV）， and trabecular separation （Tb.Sp）. Ossification was observed by saffrane-solid green staining， and serum levels of bone metabolism markers， including bone alkaline phosphatase （BALP）， osteocalcin （BGP）， type Ⅰ procollagen amino terminal propeptide （PINP）， and tartrate-resistant acid phosphatase 5b （TRACP-5b）， were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of Runx2， BMP-2， and Smad1 in rat femur were detected by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham operation group， bone trabecula in the model group was sparse. BMD， BV/TV， Tb.N， and Tb.Th were decreased （P<0.05， P<0.01）. BS/BV （P<0.05） and Tb.Sp were increased. The content of BGP， BALP， PINP， and TRACP-5b in serum was significantly increased （P<0.01）. The mRNA and protein expressions of Runx2， BMP-2， and Smad1 in rat femur were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the number of bone trabeculae in the high-dose and low-dose groups of Youguiwan was increased， and the bone microstructure was improved. BMD， BV/TV， Tb.N， and Tb.Th were increased significantly （P<0.05， P<0.01）， and BS/BV and Tb.Sp were increased. The content of bone metabolic markers decreased （P<0.05， P<0.01）. ConclusionYouguiwan has certain preventive and therapeutic effects on postmenopausal osteoporosis， and its mechanism may be related to promoting bone formation by regulating the BMP-2/Smad signaling pathway.

The mechanism of chlorogenic acid against neuropathic pain induced by cisplatin / 药学学报

This study aimed to investigate the analgesic effect of chlorogenic acid on cisplatin-induced neuropathic pain and explored the underlying molecular mechanisms. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Xinxiang Central Hospital, in compliance with the Institutional Animal Care Guidelines. Von Frey hair and a radiant heat was employed to measure mechanical allodynia and thermal hyperalgesia; Western blot was used to examine transient receptor potential vanilloid type-1 (TRPV1) protein expression in the rat dorsal root ganglion (DRG); patch clamp was used to record TRPV1 currents in DRG neurons. The experimental results showed that chlorogenic acid could attenuate cisplatin-induce mechanical allodynia and thermal hyperalgesia in rats. The expression of TRPV1 protein in DRGs was increased in cisplatin-treated rats, while chlorogenic acid also could reverse cisplatin-induced the upregulation of TRPV1 protein. Forthermore, chlorogenic acid could attenuate cisplatin-mediated the upregulation of TRPV1 current density. These above results indicated that chlorogenic acid could alleviate cisplatin-induced pain hypersensitivity through inhibition of the expression and function of TRPV1 in rats.

Research progress of optical coherence tomography and optical coherence tomography angiography in the prediction of postoperative visual acuity in patients with idiopathic epiretinal membrane / 国际眼科杂志(Guoji Yanke Zazhi)

Idiopathic epiretinal membrane(IERM)is a kind of epiretinal membrane without any other known ocular conditions, which occurs mostly in the middle-aged and elderly people over the age of 50. As IERM worsens, the structure and function of the retina in the macular region are altered, leading to symptoms like reduced vision and metamorphopsia. The pathogenesis of IERM remains unclear, and surgery is the primary treatment option. However, there is no consensus on the best time to have surgery, and there are differences in how well patients recover their vision following surgery. Optical coherence tomography(OCT)and OCT angiography(OCTA), as non-invasive and rapid diagnostic tools to observe retinal microstructure and blood flow changes in the macula, have been extensively utilized in clinical settings. The use of OCT and OCTA parameters to predict postoperative visual acuity has emerged as a hot topic in IERM research. This article provides a comprehensive review of current research on the correlation between various OCT and OCTA parameters and the prediction of postoperative visual acuity in IERM, aiming to assist clinicians in determining the optimal timing for surgery and balancing the benefits and risks involved.

Research progress of targeted pulmonary vascular endothelial dysfunction in treatment of pulmonary hypertension / 中国药理学通报

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants / 中华儿科杂志

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Humanistic Care for the Prevention of Perioperative Hypothermia in the Elderly / 中国医学伦理学

The intervention and prevention of perioperative hypothermia is not only reflected in the technical level, but also reveals the important role of humanistic care in the whole intervention work. If perioperative patients have hypothermia, it is likely to cause a series of complications such as postoperative shivering, which seriously threatens the life safety of patients. Prevention and intervention was based on a comprehensive understanding of the causes and hazards of hypothermia, especially the impact on the lives of the elderly. Effective supervision was implemented in the whole process of operation, such as dynamic monitoring of vital signs including body temperature, followed by room temperature regulation, body temperature protection and preoperative and postoperative psychological nursing. At this time, the sense of responsibility, good humanistic care of medical staff are of positive significance to effectively prevent and reduce the probability of perioperative hypothermia and accelerate the postoperative rehabilitation of patients.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

A Family with Congenital Dysfibrinogenemia and Blood Transfusion / 中国实验血液学杂志

OBJECTIVE@#To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.@*METHODS@#Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.@*RESULTS@#The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.@*CONCLUSION@#Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.

Sperm acrosin activity may be a useful factor in choosing between ICSI and IVF for infertile male patients / 亚洲男科学杂志(英文版)

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 106 sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 106 sperm) and the group with low acrosin activity (<24.78 μIU per 106 sperm). The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%, while the group with a high IVF fertilization rate had a low index of 0.2%. At an acrosin activity of <24.78 µIU per 106 sperm, in one cycle of the same patient, the fertilization rate, normal fertilization rate, and good-quality embryo rate for ICSI were significantly higher than those for IVF. Therefore, the most promising application of acrosin activity could be in the selection of ICSI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

BLOC1S1 promotes proliferation of goat spermatogonial stem cells / 生物工程学报

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.

Establishment of a nomogram model for predicting the risk of postpartum stress urinary incontinence based on pelvic floor ultrasound and clinical data / 现代泌尿外科杂志

【Objective】 To analyze the risk factors of postpartum stress urinary incontinence (SUI) and to establish a nomogram model. 【Methods】 A total of 278 puerpera who gave birth at our hospital during Dec.2018 and Aug.2020 were selected as the modeling group, and 132 puerpera who gave birth during Sep.2020 and Sep.2021 were involved in the verification group. Factors affecting postpartum SUI were identified with univariate and multivariate logistic regression, and a nomogram prediction model was constructed with R software. The predictive effectiveness and discrimination of the model were assessed, and the decision curve analysis (DCA) was drawn to evaluate the clinical application value of the model. 【Results】 A total of 84 cases (30.22%) in the modeling group developed SUI 2 months after delivery. Fetal weight, delivery method, maternal age, mobility (Δhy) and rotation Angle (Δβ) were factors affecting postpartum SUI (P<0.05). Multivariate logistic regression analysis showed that increased fetal weight, normal delivery, increased Δhy, and increased Δβ were independent risk factors of postpartum SUI (P<0.05). The constructed nomogram fitted well. The H-L fit curve of the modeling group and verification group were (χ2=7.514, P=0.312) and (χ2=6.157, P=0.267), respectively. The area under the receiver operating characteristic curve of the modeling group and verification group were 0.815 and 0.760, respectively, indicating high specificity and consistency. DCA indicated that when the high-risk threshold probability of the model was between 0.06-0.80, the nomogram model had a high clinical value. 【Conclusion】 Increased fetal weight, normal delivery, increased Δhy and elevated Δβ are independent risk factors that affect postpartum SUI. The nomogram model constructed has good predictive effectiveness and discrimination, and high clinical application value.

Psychological experiences in adolescents with non-suicidal self-injury behavior： a qualitative Meta-synthesis / 四川精神卫生

BackgroundNon-suicidal self-injury （NSSI） is a serious global public health issue and an important risk factor for suicide attempts and completed suicide. The incidence of NSSI among adolescents in China is 27.4%. Therefore， it is critical to address NSSI and prevent its progression into more severe mental health conditions. ObjectiveTo systematically evaluate the psychological experiences and needs of adolescents with NSSI behavior， so as to provide references for formulating targeted intervention strategies for this demographic. MethodsA computer search was conducted across a total of eleven databases， including Cochrane Library， Embase， PubMed， PsycINFO， Web of Science， CINAHL， Medline， CNKI， Wanfang， VIP and CBM， to gather qualitative research on the psychological experiences and needs of adolescents with NSSI behavior. The search extended from the establishment of these databases up to March， 2023. The Australian Joanna Briggs Institute （JBI） qualitative research quality evaluation tools were used to evaluate the included literature， and a Meta-synthesis method was used to integrate the results. ResultsA total of 11 studies were included， yielding 46 research findings. Similar findings were consolidated into 10 new categories， ultimately resulting in 5 synthesized outcomes， including interpersonal conflict， academic pressure and self-reflective struggles， self-injurious behaviors intertwined with inner emotions， the power of love to overcome helplessness， and adjustment and seeking positive coping strategies. ConclusionAdolescents often have experienced negative life events before NSSI behaviors， with notable conflicts in interpersonal relationships， academic pressures and family education. Following NSSI behavior， they undergo various psychological experiences， such as transient feelings of relief， dependence and guilt. In addition， they crave guidance and assistance from professionals to cope with negative emotions.［Funded by Social Psychological Service and Crisis Intervention in 2022 （number， LZXL-202213）］

Effects of autologous platelet-rich plasma combined with negative pressure wound therapy for chronic refractory wounds: a Meta-analysis / 中国输血杂志

【Objective】 To systematically evaluate the therapeutic efficacy of autologous platelet-rich plasma combined with negative pressure wound therapy on chronic refractory wounds, and to provide reference for clinical treatment. 【Methods】 Randomized controlled trials of autologous platelet-rich plasma combined with negative pressure wound therapy for the treatment of chronic refractory wounds were included in the databases of CNKI, Wan fang, VIP, PubMed, Embase and Cochrane Library from the time of database construction to November 2022. After literature screening, data extraction and quality evaluation, Meta analysis was performed using Stata 15.1 software. 【Results】 After screening, a total of 11 Chinese literatures that met the criteria of this paper were retrieved, involving a total of 359 patients with chronic refractory wounds. The observation group was treated with autologous platelet-rich plasma combined with negative pressure wound therapy, and the control group was treated with negative pressure wound therapy alone. Meta-analysis suggested that compared with negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy shortened wound healing time [WMD=-6.08, 95%CI (-7.77, -4.40), P<0.05]. The hospitalization was shortened [WMD=-8.24, 95%CI (-11.55, -4.94), P<0.05], the pain score was decreased [WMD=-1.73, 95%CI (-2.06, -1.40), P<0.05], and the positive rate of bacterial culture on the wound was decreased [RR=0.28, 95%CI(0.16, 0.49), P<0.05], the wound treatment effect was good [RR=1.28, 95%CI(1.17, 1.41), P<0.05]. 【Conclusion】 Based on current studies, compared with the negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy can effectively promote the healing of chronic refractory wounds, shorten the hospital stay, reduce pain and infection, and the clinical treatment effect is better.

Effects and mechanism of Morus alba L. (Sangzhi) alkaloids combined with metformin on glucose metabolism in diabetic KKAy mice / 药学学报

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

A preliminary study on stereotactic ablative brachytherapy for lung metastases from cervical cancer / 中国辐射卫生

Objective To preliminarily study the effectiveness and safety of stereotactic ablative brachytherapy (SABT) for lung metastases from cervical cancer. Methods We analyzed the clinical data of 18 patients with cervical cancer with lung metastasis treated with SABT to compare gross tumor volume (VGTV) and squamous cell carcinoma (SCC) antigen before and after SABT. The clinical benefit rate (CBR) and adverse reactions were recorded. Results After SABT treatment, there were significant decreases in VGTV (t=1.708, P<0.05) and the SCC antigen level (t=1.704, P<0.05). CBR reached 94.4%. Adverse reactions of grades 3-4 did not occur in any patient. Fourteen patients had mild complications, including 1 case of bloody sputum and 1 case of a small pneumothorax. Ten cases developed mild radiation-induced lung injury, with grade 2 radiation pneumonitis in 4 cases. The Karnofsky performance status score and needle depth were not associated with the occurrence of adverse reactions, while the radius of GTV and interstitial lung disease were associated with the occurrence of adverse reactions. Conclusion SABT is a safe and effective alternative to the treatment of lung metastases from cervical cancer.

Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

Historical Evolution and Modern Clinical Application of Classic Formula Wuyaotang / 中国实验方剂学杂志

The classic formula Wuyaotang is the 49th of the 100 formulas in the Catalogue of Ancient Classic Prescriptions (First Batch) issued by the National Administration of Traditional Chinese Medicine, and is from the Secrets from the Orchid Chamber (《兰室秘藏》) by LI Dongyuan of the Jin Dynasty. It is composed of Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Linderae Radix, and Cyperi Rhizoma, and has the effect of moving Qi, regulating meridians, and relieving pain. It is mainly indicated for Qi stagnation and blood stasis syndrome. Based on the ancient books on Wuyaotang, this study systematically reviewed the formula source, composition, dosage, preparation, usage, functions, indications, preparation principle, drug processing, modification, etc. of Wuyaotang with the bibliometrics method, explored its historical evolution, and determined the key information. Statistical analysis of its modern literature shows that there are few studies of the original formula of Wuyaotang, and the clinical studies mainly focus on modified Wuyaotang. It has a wide range of treatment scope and can be used for the treatment of dysmenorrhea, delayed menstrual cycle, hypomenorrhea, and menstrual fever, as well as ulcerative colitis, spleen distortion, sciatica, child intestinal spasm, and other internal, surgical, gynecological, and pediatric diseases. The pathogenesis in traditional Chinese medicine (TCM) is Qi stagnation. Through the analysis and research on ancient books and modern literature recording Wuyaotang, this study is expected to provide a scientific basis for the clinical application, in-depth research, and development of the classic formula Wuyaotang.

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Distribution of non-bacterial pathogens in 1 788 children with community-acquired pneumonia / 中国当代儿科杂志

OBJECTIVES@#To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.@*RESULTS@#Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.@*CONCLUSIONS@#MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer / 中国中药杂志

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.