Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice / 中国天然药物

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases / 中华外科杂志

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.

The influencing factors of renal response in newly diagnosed multiple myeloma patients with renal impairment / 中华血液学杂志

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.

Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists / 中华医学杂志(英文版)

BACKGROUND@#Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.@*METHODS@#Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.@*RESULTS@#A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%).@*CONCLUSION@#The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Effects of primary acquired nasolacrimal duct obstruction on tear film and ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P&#x003C;0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P&#x003E;0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

Identification of constituents in vitro and blood-absorbed ingredients of protective effect on acute liver injury from Yin Chen Hao decoction based on UPLC-QTOF/MS / 药学学报

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Effect and Mechanism of Nongsuo Dangguiwan in Relieving Oxidative Stress in Premature Ovarian Insufficiency Rats Based on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group， model group， positive drug group （Femoston， 0.3 mg·kg-1）， and high-， medium-， and low-dose groups of concentrated Nongsuo Dangguiwan （2.08， 4.16， 8.32 g·kg-1）， with six rats in each group. Rats， except for those in the normal group， were injected with 80 mg·kg-1 vinyl cyclohexene dioxide （VCD） per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day， rats were treated with corresponding drugs by gavage， while those in the model group received 2 mL·kg-1 saline， once daily for 28 consecutive days. The ovarian index， levels of related hormones including estradiol （E2）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and anti-mullerian hormone （AMH） in serum， as well as superoxide dismutase （SOD） activity and glutathione （GSH） content in serum were measured by enzyme-linked immunosorbent assay （ELISA）. The malondialdehyde （MDA） content in serum was detected by the thiobarbituric acid （TAB） method. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. The expression of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， SOD2， and SOD1 in ovarian tissues was detected by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed a significant reduction in growing follicles in the ovary， loose arrangement of granulosa cells in the follicle， decreased body weight， ovarian index， and serum AMH and E2 levels， increased LH and FSH levels （P<0.01）， reduced levels of SOD and GSH in serum （P<0.01）， and increased MDA level （P<0.01）. Compared with the model group， the groups with drug intervention showed increased ovarian index （P<0.05， P<0.01）， increased serum E2 level （P<0.05， P<0.01）， decreased FSH， AMH， and LH levels （P<0.05， P<0.01）， increased number of growing follicles in the ovary， potentiated SOD activity in serum， increased GSH content， decreased MDA content （P<0.05， P<0.01）， and up-regulated expression levels of Nrf2， HO-1， SOD2， and SOD1 proteins in ovarian tissues （P<0.05， P<0.01）. ConclusionNongsuo Dangguiwan can regulate serum hormone levels， increase the expression of Nrf2， HO-1， SOD2， and SOD1 in ovarian tissues， and improve ovarian antioxidant capacity to resist oxidative stress injury， thereby improving ovarian reserve function.

Effects of multi-disciplinary collaborative nursing on patients with transcatheter aortic valve implantation / 中国胸心血管外科临床杂志

@#Objective     To analyze the clinical intervention effect of multi-disciplinary team (MDT) nursing mode on patients after transcatheter aortic valve implantation (TAVI). Methods     A total of 89 patients who were admitted to our hospital and underwent TAVI surgery from April to December 2021 were selected, including 64 males and 25 females, with an average age of 64.7±11.8 years. The subjects were divided into a MDT intervention group (n=42) and a control group (n=47) according to different postoperative nursing intervention methods. Clinical effectivenesses were compared between the two groups. Results     The left ventricular ejection fraction in the two groups significantly increased on the 7th day after the operation, and the increase in the MDT intervention group was more obvious, with no statistical  difference between the two groups (P=0.14). On the 7th day after surgery, forced vital capacity/predicated value and forced expiratory volume in one second/predicated value significantly decreased, and decreased more significantly in the control group than those in the MDT intervention group with statistical differences (P=0.01). The ICU stay time (P=0.01), hospital stay time (P<0.01) and total postoperative pulmonary complications rate (P=0.03) in the MDT intervention group were significantly shorter or lower than those in the control group The evaluation results of the anxiety and depression status of the patients before and after nursing intervention showed that the scores of anxiety and depression in the two groups were significantly lower than before, and the scores of each scale in the MDT intervention group were lower. The score of quality of life of the two groups significantly improved at the end of 6 months after surgery, and in the MDT intervention group it was significantly higher than that in the control group (P=0.02). Conclusion     MDT intervention mode can promote the rapid recovery of patients after TAVI, effectively reduce the risk of postoperative pulmonary complications, and improve the postoperative quality of life.

Effect of early off-bed mobility on diaphragm function in intensive care unit patients undergoing mechanical ventilation / 中华危重病急救医学

Objective:To explore the improvement of diaphragm function after early off-bed mobility intervention in intensive care unit (ICU) patients undergoing mechanical ventilation.Methods:A randomized controlled trial was conducted. A total of 147 adult patients undergoing mechanical ventilation admitted to ICU of Affiliated Hospital of Zunyi Medical University from October 2019 to March 2022 were enrolled. The patients were divided into control group and observation group by convenient sampling. Except for the different intervention programs of early mobility, other treatment and nursing of the patients in the two groups were carried out according to ICU routine. Progressive early activities were performed in the control group, while early off-bed mobility was performed in the observation group. The changes of diaphragm thickness at the end of inspiratory (DTei), diaphragm thickness at the end of expiratory (DTee) and diaphragm thickening fraction (DTF) before and 24, 48, 72 and 96 hours of intervention, and the duration of mechanical ventilation, length of ICU stay and 24-hour re-intubation rate after intervention were compared between the two groups.Results:Among the 147 patients, there were 4 cases of detachment in the control group and 5 cases of detachment in the observation group. Finally, 138 patients were enrolled, 69 cases in the control group and 69 cases in the observation group. There was no significant difference in gender, age, diagnosis of ICU, sedatives, muscle strength, ventilator model, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and DTei, DTee, DTF before intervention between the two groups. The DTei, DTee and DTF in both groups were increased gradually with the extension of intervention time, especially in the observation group [DTei (cm) at 24, 48, 72 and 96 hours of intervention in the observation group were 0.247±0.014, 0.275±0.016, 0.300±0.013 and 0.329±0.013, while in the control group were 0.242±0.015, 0.258±0.013, 0.269±0.014, and 0.290±0.017, effect of time: F = 993.825, P = 0.000, effect of intervention: F = 82.304, P = 0.000, interaction effect between intervention and time: F = 84.457, P = 0.000; DTee (cm) of the observation group were 0.213±0.014, 0.227±0.013, 0.243±0.016, 0.264±0.010, while in the control group were 0.213±0.016, 0.218±0.013, 0.224±0.013, 0.234±0.014, effect of time: F = 385.552, P = 0.000, effect of intervention: F = 28.161, P = 0.000, interaction effect between intervention and time: F = 45.012, P = 0.000; DTF of the observation group were (15.98±4.23)%, (21.35±4.67)%, (24.09±4.44)% and (25.24±3.74)%, while in the control group were (14.17±4.66)%, (18.11±3.92)%, (20.22±4.19)% and (20.98±4.12)%, effect of time: F = 161.552, P = 0.000, effect of intervention: F = 49.224, P = 0.000, interaction effect between intervention and time: F = -4.507, P = 0.000]. The duration of mechanical ventilation and length of ICU stay in the observation group were significantly shorter than those in the control group [duration of mechanical ventilation (hours): 112.68±12.25 vs. 135.32±22.10, length of ICU stay (days): 7.84±1.78 vs. 10.23±2.43, both P < 0.01]. However, there was no significant difference in 24-hour re-intubation rate between the observation group and the control group (0% vs. 2.90%, P > 0.05). Conclusions:Both early off-bed mobility and progressive early activities can prevent diaphragm weakness in ICU patients undergoing mechanical ventilation, and the effect of early off-bed mobility is better. Early off-bed mobility can significantly shorten the duration of mechanical ventilation and length of ICU stay, and it is safe and feasible.

MicroRNA21-5p alleviates hyperoxia-induced acute lung injury in rats through activating phosphatidylinositol 3 kinase/serine-threonine protein kinase signaling pathway by regulating type Ⅱ alveolar epithelial cell apoptosis / 中华危重病急救医学

Objective:To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type Ⅱ alveolar epithelial cell (AECⅡ).Methods:Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 μL titer (1×10 12 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AECⅡ cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. Results:Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AECⅡ cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AECⅡ cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AECⅡ cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (μg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1β (μg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AECⅡ cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg≈0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2 -ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AECⅡ cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. Conclusion:miR-21-5p attenuates HALI by inhibiting AECⅡ cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.

Wrist-ankle acupuncture combined with rehabilitation for dysphagia caused by achalasia of cricopharyngeal muscle after stroke / 中国基层医药

Objective:To investigate the clinical efficacy of wrist-ankle acupuncture combined with rehabilitation for dysphagia caused by achalasia of the cricopharyngeal muscle after stroke.Methods:Sixty patients with dysphagia caused by achalasia of the cricopharyngeal muscle after stroke who received treatment in Wenzhou Hospital of Traditional Chinese Medicine from June 2019 to March 2020 were included in this study. They were randomly divided into a treatment group and a control group ( n = 30). All patients received routine drug treatment and swallowing rehabilitation training. The control group underwent routine acupuncture treatment. The treatment group received wrist-ankle acupuncture based on routine acupuncture treatment. Both groups were treated for 4 consecutive weeks. The clinical efficacy in the two groups was evaluated using the Video Fluoroscopic Swallowing Study (VFSS), Standardized Swallowing Assessment (SSA), and Swallow Quality-of-Life Questionnaire (SWAL-QOL). Results:Before treatment, there were no significant differences in VFSS, SSA, and SWAL-QOL scores between the two groups. After treatment, VFSS, SSA, and SWAL-QOL scores in the treatment group were (8.21 ± 0.77) points, (21.19 ± 1.42) points, (200.24 ± 11.12) points, and they were (6.01 ± 0.36) points, (23.31 ± 1.45) points, and (182.37 ± 12.06) points in the control group ( t = 3.26, 5.50, 6.31, all P < 0.05). Conclusion:Wrist-ankle acupuncture combined with rehabilitation is an effective treatment method for dysphagia caused by achalasia of the cricopharyngeal muscle after stroke. It can alleviate dysphagia and improve quality of life.

Research progress of phosphoglycerate mutase 5-mediated mitophagy and necroptosis / 中华危重病急救医学

Mitophagy is the selective degradation of damaged mitochondria, and it is of great significance to maintain the normal quantity and quality of mitochondria to ensure cell homeostasis and survival. Necroptosis is a type of programmed cell necrosis that can be induced by excessive mitophagy. Reactive oxygen species (ROS) are produced mainly by mitochondria and can damage mitochondria. Hyperoxic acute lung injury (HALI) is a serious complication of clinical oxygen therapy, and its pathogenesis is not clear. Existing studies have shown that mitophagy and necroptosis are involved in the occurrence of HALI. There are many mechanisms regulating mitophagy and necroptosis, including tumor necrosis factor-α (TNF-α), E3 ubiquitin protein ligase (PINK1/Parkin) protein pathway encoded by PTEN-induced kinase 1/PARK2 gene, phosphoglycerate mutase 5 (PGAM5), etc. PGAM5 has been proved to be a key factor linking mitophagy and necroptosis. Previous studies of our team found that the mechanism of microRNA-21-5p (miR-21-5p) alleviating HALI was related to its pGAM5-mediated inhibition of mitophagy, but the mechanism of PGAM5-mediated mitophagy and necroptosis remains unclear. Therefore, this paper reviews the targets of PGAM5-mediated mitophagy and necroptosis, in order to find clues of lung protection of pGAM5-mediated mitophagy and necroptosis in HALI, and provide theoretical basis for subsequent basic research.

Role and mechanism of signal transducer and activator of transcription protein STAT1/3/5 in hyperoxia-induced acute lung injury / 中华危重病急救医学

Objective:To investigate whether signal transducer and activator of transcription (STAT1/3/5) have a protective effect on hyperoxia-induced acute lung injury (HALI) and its mechanism.Methods:Seventy C57BL/6J mice were randomly divided into five groups: normoxia control group, HALI group, and STAT1/3/5 inhibitor groups, with 14 mice in each group. The HALI model was established by exposure to more than 90% hyperoxia for 48 hours; three STAT inhibitor groups were pretreated by intraperitoneal injection of STAT1 inhibitor 40 mg/kg and STAT3 inhibitor 5 mg/kg, and STAT5 inhibitor 10 mg/kg for 1 week. Six blood samples were randomly collected from each group, and microRNA-21 (miR-21) expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Lung tissue of the sacrificed mice was obtained, and enzyme linked immunosorbent assay (ELISA) was used to detect the contents of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), superoxide dismutase (SOD), malonic dialdehyde (MDA), and matrix metalloproteinase 9 (MMP9). The water content of lung tissue was calculated. The pathological changes in lung tissue were observed under the light microscope, and the pathological score of lung injury was performed. Western blotting was used to detect the expression of phosphorylated STAT (p-STAT1, p-STAT3, p-STAT5) in lung tissue. The 7-day cumulative survival rates of the remaining 8 mice in each group were analyzed using Kaplan-Meier survival curves.Results:Under the light microscope, the alveolar structures in the HALI group and the STAT1 inhibitor group were destroyed, a large number of neutrophils (NEU) infiltrated in the alveoli and lung interstitium, which were thickened. The pathological score of lung injury and the water content of the lung tissue was significantly increased. In STAT3 inhibitor and STAT5 inhibitor groups, the alveolar cavity was clear, the degree of NEU infiltration and the thickness of lung interstitium were lower than those in HALI group, the pathological score of lung injury and the water content of lung tissue were significantly decreased, especially in STAT3 inhibitor group. Compared with the normoxia control group, the contents of TNF-α, IL-6, IL-1β, MDA, and MMP9, and the expression levels of p-STAT3 and p-STAT5 in the HALI group were significantly increased. In contrast, the content of SOD and the expression of miR-21 were significantly decreased. Compared with the HALI group, the contents of TNF-α, IL-6, IL-1β, MDA, and MMP9 in the STAT3 inhibitor group and STAT5 inhibitor group were significantly decreased. At the same time, the content of SOD and the expression of miR-21 were significantly increased, especially in STAT3 inhibitor group [TNF-α (μg/L): 42.53±3.25 vs. 86.36±5.48, IL-6 (ng/L): 68.46±4.28 vs. 145.00±6.89, IL-1β (μg/L): 28.74±3.53 vs. 68.00±5.64, MDA (μmol/g): 20.33±2.74 vs. 42.58±3.45, and MMP9 (ng/L): 128.55±6.35 vs. 325.13±6.65, SOD (kU/g): 50.53±4.19 vs. 22.53±3.27, miR-21 (2 -ΔΔCt): 0.550±0.018 vs. 0.316±0.037, all P < 0.05]. Kaplan-Meier survival curve analysis showed that the 7-day cumulative survival rates of the STAT3 inhibitor group and STAT5 inhibitor group were significantly higher than those of the HALI group [62.5% (5/8), 37.5% (3/8) vs. 12.5% (1/8), both P < 0.05]. Conclusion:Inhibition of STAT3 hyperactivation may suppress the inflammatory response, regulate oxidative stress, improve lung permeability through regulating the expression of miR-21, which exert lung protection in HALI.

Effect of Jianpi Yishen Huazhuo Prescription on Ovarian Function in Rats with Polycystic Ovary Syndrome Based on NLRP3 Inflammatory Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg-1·d-1）， and 10 in the low （1.275 g·kg-1·d-1）， medium （2.55 g·kg-1·d-1）， and high-dose （5.10 g·kg-1·d-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg-1·d-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg-1·d-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E2） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E2 decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E2 and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.

Liuwei Dihuangtang Alleviates Myelin Injury in Anterior Cingulate Cortex and Depression-like Behaviors of Rats with Diabetes Mellitus and Depression via Promoting Autophagy and Regulating Microglial Phenotype / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang （LWDHT） on depression-like behaviors of rats with diabetes mellitus and depression （DD） and explore its mechanism. MethodThe diabetes mellitus （DM） model was induced by the high-fat diet and tail vein injection of low-dose streptozotocin （STZ） in 50 male Sprague-Dawley rats of SPF grade. Then the DD model was induced by chronic unpredictable mild stress （CUMS） for 28 days in DM rats. Fifty DD rats were randomly divided into model group， fluoxetine group （10 mg·kg-1·d-1）， and low-， medium-， and high-dose LWDHT groups （3.375， 6.75， 13.5 g·kg-1·d-1）， with 10 rats in each group. Another 10 healthy rats were assigned into a control group and received normal saline by gavage. After four weeks of drug intervention， the forced swimming assay was carried out to assess the depression-like behaviors of rats. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in the anterior cingulate cortex （ACC） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to detect the expression of myelin basic protein （MBP） in ACC and the co-localization of ionized calcium-binding adapter molecule 1 （Iba1） with intracellular microtubule-associated protein 1 light chain 3 （LC3）. The protein expression levels of MBP， myelin proteolipid protein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， Beclin-1， LC3， p62， and microglia （MG） phenotypic protein-related inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg1） were detected by Western blot. ResultCompared with the control group， the model group showed shortened swimming time and prolonged immobility time （P<0.01）. Compared with the model group， the medium- and high-dose LWDHT groups showed reduced immobility time （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased protein expression of MBP， PLP， and MOG in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated protein expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased MBP fluorescence intensity in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased MBP fluorescence intensity in the ACC region （P<0.05， P<0.01）. Compared with the control group， the model group showed increased expression of iNOS （P<0.01） and slightly increased Arg1 protein expression. Compared with the model group， the medium- and high-dose LWDHT groups and the fluoxetine group showed down-regulated iNOS expression and up-regulated Arg1 protein expression （P<0.05， P<0.01）， but there was no significant difference between the fluoxetine group and the medium-，high-dose LWDHT groups. Compared with the control group， the model group showed increased expression levels of proinflammatory factors IL-1β and TNF-α in the ACC region （P<0.01） and slightly increased expression levels of anti-inflammatory factors IL-4 and IL-10. Compared with the model group， the fluoxetine group， and the medium- and high-dose LWDHT groups showed down-regulated expression of IL-1β and TNF-α （P<0.05， P<0.01） and up-regulated expression of IL-4 and IL-10 （P<0.05， P<0.01）. Compared with the control group， the model group showed reduced expression levels of Beclin-1 and LC3Ⅱ （P<0.01） and increased expression level of p62 （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated Beclin-1 and LC3Ⅱ expression （P<0.01） and down-regulated p62 expression （P<0.01）. Compared with the control group， the model group showed decreased LC3+Iba1+ cells in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased LC3+Iba1+ cells （P<0.05， P<0.01）. ConclusionLWDHT can alleviate the depression-like behaviors in DD rats presumedly by promoting MG autophagy， regulating MG phenotypic changes， and increasing MG clearance of myelin sheath fragments. Meanwhile， MG phenotypic transformation also inhibits ACC inflammation in DD rats， improves the local microenvironment of oligodendrocyte proliferation and differentiation， and ultimately promotes the repair and remyelination of damaged myelin sheath.

Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro / 中西医结合学报

OBJECTIVE@#Qili Qiangxin (QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxia-reoxygenation (H/R)-induced myocardial injury model.@*METHODS@#The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia-reperfusion injury. Apoptosis, autophagy, and generation of reactive oxygen species (ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.@*RESULTS@#Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3II and p62 degradation (P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 μmol/L), and QLQX (250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis (P < 0.01), while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger, N-Acetyl-L-cysteine (NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy (P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK (P < 0.01), which showed a similar effect to QLQX.@*CONCLUSION@#QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.

A Case Report of Cyclic Thrombocytopenia with Periodic Anemia / 罕见病研究

Cyclic thrombocytopenia (CTP) is a rare hemorrhagic disorder characterized by cutaneous and mucosal bleeding and periodic fluctuations platelet count. The clinical characteristics and treatment response of a patient with CTP were analyzed. The patient is a 30-year-old male with recurrent cutaneous and mucosal bleeding for 5 years. Skin petechiae, oral blood blister, conjunctival hemorrhage, by tracing the history, monitoring changes in blood routine diagnosis of CTP, further testing of reticulocyte platelets and platelet hormone, and periodically promoting bone marrow megakaryocyte with changes of platelet, confirmed that the patient's periodic reduction in bone marrow hematopoiesis, was causing more damage. Periodic changes of reticulocyte, erythropoietin and erythroid hematopoiesis in bone marrow were also observed. The patient had normal Treg levels, no significant telomere length shortening in peripheral blood nucleated cells, and no clear pathogenic gene mutation was found by whole exon gene sequencing. Recombinant human thrombopoietin(rhTPO) treatment shortened the time of thrombocytopenia and increased the minimum platelet value. The average age of onset of CTP was 35 years old, some patients had severe bleeding, and more than half of the patients were misdiagnosed as primary immune thrombocytopenia. At present, the pathogenesis of CTP has not been clarified and there is no effective treatment. The experience of this patient suggests that rhTPO may be effective. This case of CTP complicated with periodic anemia is the first report. The exploration of its pathogenesis provides important information for understanding CTP.

Relation between sleep duration and brachial-ankle pulse wave velocity in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

To explore the relationship between sleep duration and brachial-ankle pulse wave velocity(baPWV) in patients with type 2 diabetes mellitus(T2DM). A total of 1 755 patients with T2DM received standardized management of metabolic disease from March 1, 2018 to February 29, 2020 were included. All patients were classified into three groups according to the sleep duration: short(≤6 h), medium(>6 h to 8 h) and long(>8 h). Increased arterial stiffness was defined as baPWV≥1 600 cm/s. The prevalence of baPWV≥1 600 cm/s was 39.7%, 30.8% and 38.6% in short, medium and long sleep duration group, respectively( P<0.01). Multivariate logistic regression analysis showed that patients with long sleep duration( OR=1.317, P<0.05) but not short sleep duration( OR=1.169, P>0.05) had a higher risk for baPWV≥1 600 cm/s compared with the reference group with medium sleep duration. Stratified analyses by sex showed that the OR were 1.735( P<0.05) among female and 1.131( P>0.05) among male respectively for baPWV≥1 600 cm/s in long sleep duration group when compared with medium sleep duration group. Sleep duration>8 h was found to be associated with elevated baPWV in patients with T2DM. There were gender differences in the correlation between long sleep duration and baPWV.

Research progress of extracellular vesicle microRNA in acute lung injury / 中华危重病急救医学

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by the destruction of the barrier function of alveolar epithelial cells and capillary endothelial cells and the recruitment of inflammatory cells, which leads to alveolar and interstitial edema, hyaline membrane formation and inflammatory infiltration of the lungs, etc. The mechanism is not completely defined. The current treatment plan focuses on comprehensive treatments such as ventilator support treatment, fluid management, and nutritional support, but the prognosis is still poor. Studies have shown that extracellular vesicle microRNA (miRNA) from different sources participate in regulating the function of epithelial cells, endothelial cells and phagocytes in different ways, thus aggravating or improving ALI, and have diagnostic, differential diagnosis and the therapeutic value. In this article, the mechanism, diagnostic and differerntial value of extracellular vesicle miRNA from different sources in ALI and the therapy of extracellular vesicle miRNA from stem cell in ALI are reviewed.

The effects of agmatine on the apoptosis of immune cells in septic rats / 中华急诊医学杂志

Objective:By establishing the rats model of sepsis induced by endotoxin, exploring the effects of agmatine on the apoptosis of splenocyte and dendritic cells in the septic rats.Methods:SD rats ( healthy and clean, male, 90) were randomly(random number) divided into control groups, endotoxin groups and agmatine groups, 30 rats per group. The control groups were injected with normal saline via femoral vein (10 mL/kg), endotoxin groups were injected with lipopolysaccharide via femoral vein (10 mg/kg), agmatine groups were injected with lipopolysaccharide via femoral vein (10 mL/kg) and intraperitoneal injected of agmatine (200 mg/kg).The three groups were randomly selected 10 rats separately at 0 h, 12 h, 24 h (marked as 0 h, 12 h, 24 h subgroups, n=10) , anesthetized to death. Weigh the spleen; HE staining was used to observe the pathological changes of the spleen; The cell apoptosis of splenocyte and dendritic cells were detected by flow cytometry. The results were statistically analyzed using SPSS 17.0 software, analyzed by independent sample t test, P<0.05 was considered statistically significant. Results:The weights (g) of spleen in 12 h (1.2633±0.0652) , 24 h (1.5576±0.0711) subgroups of the endotoxin groups were increased significantly than the corresponding subgroups[(0.8876±0.0361),(0.9079±0.0425)]of the control groups ( P<0.05) , the 12 h (1.1052±0.0585) , 24 h (1.3262±0.0682) subgroups of the agmatine groups were decreased significantly than the corresponding subgroups of the endotoxin groups ( P<0.05) . HE staining showed that the spleen tissue inflammatory reaction in the endotoxin groups were worse than the control group ( P<0.05) , the agmatine groups were better than the endotoxin group ( P<0.05) . The apoptosis rates of the splenocyte[(13.31±1.26)、(19.53±1.68)]and dendritic cells[(19.5±1.52)、(16.09±1.15)]in the spleen from 12 h, 24 h subgroups of the endotoxin groups were significantly higher than the corresponding subgroups[(6.27±0.71),(6.01±0.67) and (4.99±0.51)、(5.30±0.66)]of the control groups ( P<0.05) , the 12 h[(9.19±0.95),(12.19±1.25)], 24 h [(12.71±1.19),(10.76±1.09)subgroups of the agmatine groups were significantly lower than the corresponding subgroups of the endotoxin groups ( P<0.05) ; The apoptosis rates of the splenocyte in the 24 h subgroups of the endotoxin groups and the agmatine groups were significantly higher than the 12 h subgroups of the same group ( P<0.05) , but the apoptosis rates of the dendritic cells were significantly lower than the 12h subgroups of the same group ( P<0.05) . Conclusion:The apoptosis of splenocyte and dendritic cells were closely related to the occurrence and development of sepsis, Agmatine could inhibit the apoptosis of splenocyte and dendritic cells the rats with sepsis.