Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months / 中国当代儿科杂志

OBJECTIVES@#To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants.@*METHODS@#A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.@*RESULTS@#The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively.@*CONCLUSIONS@#SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

Safety of modified T-piece resuscitator versus nasal cannula oxygen in electronic bronchoscopy for infants: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy.@*METHODS@#A prospective randomized, controlled, and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021. These infants were divided into a nasal cannula (NC) group and a modified T-piece resuscitator (TPR) group using a random number table. The lowest intraoperative blood oxygen saturation was recorded as the primary outcome, and intraoperative heart rate and respiratory results were recorded as the secondary outcomes.@*RESULTS@#Compared with the NC group, the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia (P<0.05). In the modified TPR group, there were 6 infants with mild hypoxemia, 2 with moderate hypoxemia, and 1 with severe hypoxemia, while in the NC group, there were 3 infants with mild hypoxemia, 5 with moderate hypoxemia, and 9 with severe hypoxemia (P<0.05). The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group (P<0.05), but there was no significant difference in the incidence rate of arrhythmias between the two groups (P>0.05).@*CONCLUSIONS@#Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy, and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.

Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion / 药学学报

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.

Recent progress of targeting Nrf2-ferroptosis to treat brain injury after ischemic stroke / 中国临床药理学与治疗学

Emerging evidences suggest that ferroptosis plays a vital role in the pathophysiological process of brain injury after Ischemic stroke. Accumulating evidence supports pharmacological inhibition of ferroptosis as a therapeutic target for brain injury after Ischemic stroke through activating nuclear factor erythroid 2-related factor 2 (Nrf2), which transcriptionally controls many key components of the ferroptosis pathway. In this review, briefly describe ferroptosis processes and the roles they play in contributing to brain injury after ischemic stroke in the brain. We then provide a critical overview of the relationship between Nrf2 signalling and ferroptosis. With a focus on discuss how therapeutic modulation of the Nrf2 pathway is a viable strategy to explore in the treatment of ferroptosis-driven brain injury after Ischemic stroke.

Relationship between cerebrovascular reserve capacity and white matter lesions in the elderly based on magnetic resonance imaging / 中国辐射卫生

Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.

Determination of deuterium incorporation of new drug donafenib tosilate by two methods of LC-MS with natural isotope abundance correction and 1H NMR relative quantitative method / 药学学报

An LC-MS method with natural isotope abundance correction and a 1H NMR relative quantitative method were established to determine the deuterium incorporation of donafenib tosilate, a new deuterated drug molecule. First, the peak areas of isotopic impurities (non-deuterated and incompletely deuterated impurities) and deuterated drug were recorded through the single ion monitoring (SIM) mode of the established LC-MS method and then corrected in terms of the natural isotope abundance offered by ChemDraw soft, removing the nature isotope interference from 13C, 37Cl, etc. The corrected areas were subsequently used to calculate mol% of isotopologues (D0, D1, D2, D3) and Atom% D, namely, deuterium incorporation. In addition, a 1H qNMR experiment was conducted with the aromatic proton at δ 8.63 and the residual proton of isotopic impurities at δ 2.79 as quantitative peaks. The mixture of DMSO-d6 and D2O (10∶1) was employed as the solvent to change the spin-coupling between the residual proton and active hydrogen so that the residual proton could be measured as the single peak, and the sensitivity was greatly improved. The acquisition parameters were also optimized, and Atom% 1H and the deuterium incorporation were then calculated. The two methods were applied to samples of three commercial batches, and the testing results were almost consistent. Both methods proved accurate, sensitive, fast and independent of standard substances and accurate weighing, which could be applied to the determination of the deuterium incorporation of donafenib tosilate and provide a reference for other deuterated drugs.

Correlation between Serum Osteoprotegerin/Soluble Receptor Activator of Nuclear Factor-κβ Ligand Levels and the Left Ventricular Diastolic Dysfunction in Type 2 Diabetes / 中山大学学报(医学科学版)

ObjectiveTo study the possible correlation between serum osteoprotegerin （OPG）/soluble receptor activator of the nuclear factor κB ligand （sRANKL） levels and the left ventricular diastolic dysfunction （LADD） in patients with type 2 diabetes mellitus （T2DM）. MethodsTotally 68 T2DM patients and 37 healthy controls were selected. Serum OPG and sRANKL were determined by solid-phase enzyme-linked immunosorbent assay （ELISA）. The left ventricular diastolic function of T2DM patients was measured by transthoracic echocardiography， where E/A < 1 were regarded as LVDD. T2DM patients were further divided into two subgroups according to E/A ratio （E/A≥1.0 and E/A<1）. Spearman correlation analysis， logistic regression and ROC curves were used to assess the possible correlation between serum OPG/sRANKL and LADD in T2DM patients. ResultsCompared with the healthy controls， serum OPG level in T2DM patients was higher with statistically significant difference （P <0.01）， while serum sRANKL level was lower without statistically significant difference （P =0.32）. T2DM patients with E/A<1 had significantly higher OPG level and lower sRANKL level than those with E/A≥1（P <0.01） in subgroup analysis. Spearman correlation analysis showed serum OPG level was negatively correlated with E/A ratio， while sRANKL was positively related with E/A ratio. In single factor logistic regression analyses， serum OPG ［OR （95% CI）=1.068 （1.031， 1.106）， P<0.001］ and sRANKL ［OR （95% CI）=0.976 （0.959， 0.992）， P=0.003］ were significant correlation with LVDD in T2DM patients. ROC curve analysis showed that the sensitivity and specificity of combined OPG and sRANKL in diagnosing T2DM patients LADD were 78.13% and 88.3%， respectively （area under the curve： 0.857； 95% CI=（0.768， 0.946）； P<0.001）. ConclusionsThe elevated OPG and decreased sRANKL levels may be associated with LADD in T2DM patients.

Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction / 中国中药杂志

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Experimental study of transplantation of human umbilical cord mesenchymal stem cells in the treatment of alkali-burned cornea / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of transplantation of human umbilical cord mesenchymal stem cells(hUCMSCs)in the treatment of corneal alkali burn in rabbits, and study the infiltration of polymorphonuclear neutrophils(PMNs)and the changes of vascular endothelial growth factor(VEGF)expression.METHODS: Corneal alkali burn models were established in right eyes of 75 healthy Japanese white rabbits, which were divided into three groups(group A, B and C), with 25 rabbits in each group. Group A was treated with amniotic membrane combined with hUCMSCs on the day after corneal alkali burn. Group B was treated with amniotic membrane only. Group C did not give any treatment after corneal alkali burn. At 3, 7, 14, 21 and 28d after corneal alkali burn, the corneal recovery was observed by slit lamp and photographed, the growth of corneal neovascularization(CNV)was scored, and corneal tissue was separated to make pathological sections. PMNs infiltration was observed by hematoxylin-eosin(HE)staining, and the expression of VEGF was determined by immunohistochemical staining.RESULTS: The growth of CNV in group A was much slower than that in group B at 14d after alkali burn. The CNV growth score around lesions of group A was significantly lower than that of group B(P&#x003C;0.05). The quantity of PMNs increased on the 3d with the stromal layer of cornea infiltrated, relatively decreased on the 7d, shown a peak on the 14d, and then decreased gradually. Early infiltration after alkali burn was in the corneal stroma of the lesion area, and the extent of infiltration was equal to the ulcer area at later stage. The cell densities of corneal PMNs in group A and group B were significantly lower than those in group C at all time points after alkali burns(P&#x003C;0.05), and those in group A were significantly lower than group B at 14 and 21d(P&#x003C;0.05). The expression levels of corneal VEGF in all groups after alkali burn reached peak at 7～14d and decreased significantly at 28d, and the expression levels of VEGF in group A and group B at all time points after alkali burn were significantly lower than those in group C(P&#x003C;0.05), and group A was significantly lower than that in group B at 7, 14 and 21d(P&#x003C;0.05).CONCLUSION: The transplantation of hUCMSCs after alkali burn cornea can reduce the formation of CNV and inhibit corneal revascularization after alkali burn. The corneal pathological lesions and vascularization are closely related to PMNs and VEGF.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study / 中国结合医学杂志

OBJECTIVE@#To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated.@*METHODS@#A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.@*RESULTS@#Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05).@*CONCLUSIONS@#ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Clinical features of autoimmune glial fibrillary acidic protein astrocytopathy in children: an analysis of 34 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).@*METHODS@#A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis.@*RESULTS@#The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis.@*CONCLUSIONS@#Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.

Characterization of the protein expression and localization of hnRNP family members during murine spermatogenesis / 亚洲男科学杂志(英文版)

Mammalian testis exhibits remarkably high transcriptome complexity, and spermatogenesis undergoes two periods of transcriptional cessation. These make the RNA-binding proteins (RBPs) the utmost importance during male germ cell development. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of RBPs implicated in many steps of RNA processing; however, their roles in spermatogenesis are largely unknown. Here, we investigated the expression pattern of 12 hnRNP family members in mouse testes and found that most detected members are highly expressed in the testis. Furthermore, we found that most of the detected hnRNP proteins (hnRNPD, hnRNPK, hnRNPQ, hnRNPU, and hnRNPUL1) display the highest signals in the nuclei of pachytene spermatocytes, round spermatids, and Sertoli cells, whereas hnRNPE1 exclusively concentrates in the manchette of elongating spermatids. The expression of these hnRNP proteins showed both similarities and specificity, suggesting their diverse roles in spermatogenesis.

Adjuvant rice optimization of rice-steamed Rehmanniae Radix and its anti-osteoporosis effect / 中国中药杂志

The present study aimed to investigate the effect of various adjuvant rice on the quality of rice-steamed Rehmanniae Radix(RSRR) with Japonica rice, millet, yellow rice, black rice, and glutinous rice as raw materials, and analyze the anti-osteoporosis effect of RSRR by the optimal adjuvant rice. On the basis of the established UPLC-MS/MS method for the determination of the content of catalpol and rehmannioside D, comprehensive weighted scoring method was employed to evaluate the effect of various auxiliary rice on the quality of RSRR with the content of catalpol and rehmannioside D, character score, and taste score as indicators to optimize adjuvant rice. The osteoporosis model was induced by ovariectomy in rats. SD rats were randomly divided into a sham operation group, a model group, a positive control group, and low-dose and high-dose groups of Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, and Epimedii Folium-RSRR. After treatment for 12 weeks, body weight, bone calcium content, and bone mineral density were mea-sured. The results showed that Japonica rice was selected as the optimal adjuvant due to the highest comprehensive score of RSRR steamed by Japonica rice. Rehmanniae Radix, RSRR, steamed Rehmanniae Radix, as well as Epimedii Folium-RSRR, could improve osteoporosis by increasing bone calcium content and bone mineral density. RSRR was superior to Rehmanniae Radix in improving osteo-porosis. However, there was no significant difference between RSRR and steamed Rehmanniae Radix. This study confirmed that Japo-nica rice was the optimal adjuvant rice of RSRR and verified the anti-osteoporosis effect of RSRR, which laid a foundation for further research on the pharmacological action and mechanism of RSRR.

Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging / 中国医学科学院学报

Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.

Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

Efficacy of different frequency of intense pulsed light in the treatment of meibomian gland dysfunction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy and safety of frequency of intense pulsed light(IPL)in the treatment of meibomian gland dysfunction.METHODS: In this retrospective study, a total of 108 patients(216 eyes)with meibomian gland dysfunction admitted to our hospital from January 2021 to June 2022 were included. They were divided into two groups, with 54 cases(108 eyes)IPL group(energy density 13.0J/cm2, pulse width 6ms, delay time 50ms), and 54 cases(108 eyes)in advanced optimal pulsed technology(AOPT)group(energy density 10.0-16.0J/cm2, pulse width 7-4-4 ms in unequal-division mode). The clinical effects of the two groups were observed and compared, including ocular surface symptoms, corneal fluorescein staining score(FL), tear film lipid layer thickness(LLT), ocular surface disease index(OSDI)score, mean non-invasive tear film break-up time(NIBUTav)and first non-invasive tear film break-up time(NIBUTf), tear meniscus height, score of meibomian gland secretion and its secretion traits, and the incidence of adverse effects was also calculated.RESULTS: The effective rate of the AOPT group(106 eyes, 98.1%)was higher than that of the IPL group(90 eyes, 83.3%, P&#x003C;0.05), as well as OSDI score, FL score, score of meibomian gland secretion and its secretion traits, LLT NIBUTav, NIBUTf and tear meniscus height(all P&#x003C;0.001). However, the incidence of adverse effects of the AOPT group(18 eyes, 16.7%)was higher than that of the IPL group(4 eyes, 3.7%; P&#x003C;0.05).CONCLUSION: With significant improvement in the ocular surface symptoms and function, AOPT has a better therapeutic effect on the treatment of meibomian gland dysfunction, but it has more adverse reactions. Therefore, optimal treatment plan should be fully selected in combination with the actual clinical situation.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

Responses of blood parameters and hemoglobin subtypes in plateau zokors and plateau pikas to different altitude habitats / 生理学报

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α2β2 and fetal α2ε2 hemoglobins were identified, while erythrocytes of plateau zokors only had adult α2β2 hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.