Application of pressure-controlled ventilation-volume guaranteed ventilation mode in neonatal thora-coscopic esophageal atresia surgery / 临床麻醉学杂志

Objective To investigate the ventilation effect and application safety of pressure-con-trolled ventilation-volume guaranteed(PCV-VG)mode in neonatal thoracoscopic esophageal atresia surgery.Methods Thirty-six newborns who underwent thoracoscopic esophageal atresia surgery under general anes-thesia,22 males and 14 females,aged 1-4 days,weighing 1.4-4.5 kg,ASA physical status Ⅲ or Ⅳ,were divided into two groups using a random number table method:the PCV-VG mode group(group P)and the volume-controlled ventilation(VCV)mode group(group V),18 newborns in each group.After anes-thesia,PCV-VG and VCV ventilation modes were employed for mechanical ventilation in groups P and V,respectively.The MAP,HR,and SpO2 were recorded prior to tracheal intubation,10 minutes before one-lung ventilation(OLV),30 minutes after OLV,and 10 minutes after completion of OLV.Additionally,the Pmean,Ppeak,Pplat,Cdyn,PETCO2,PaCO2,PaO2,and pH were monitored 10 minutes before OLV,30 minutes after OLV,and 10 minutes after completion of OLV.The time of tracheal tube removal after surgery and the duration of ICU retention were also observed.Results Compared with group V,the SpO2,Cdyn,PaO2,and pH levels showed a significant increase,while significant decrease were noted in Pmean,Ppeak,and Pplat in group P 30 minutes after OLV(P＜0.05).Compared with group V,the PETCO2 and PaCO2 in group P decreased significantly 30 minutes after OLV and 10 minutes after completion of OLV.Be-sides,compared with group V,the time of tracheal tube removal after surgery and the duration of ICU reten-tion were also significantly shortened in group P(P＜0.05).Conclusion The utilization of PCV-VG ven-tilation mode in neonatal thoracoscopic esophageal atresia surgery,as compared to VCV ventilation mode,can effectively reduce airway pressure,enhance lung compliance,optimize intraoperative lung gas exchange,and facilitate postoperative recovery of the neonates.

Issues in and solutions to writing investigator-initiated clinical research protocols from a scientific eval-uation perspective / 现代医院

The number of investigator initiate trials(IIT)is increasing,and a detailed scientific clinical trial protocol is an important prerequisite for ensuring the success of clinical trials and obtaining reliable and accurate results.In this study,132 scien-tific research projects taken by the researchers of a tertiary hospital were reviewed to summarize and analyze the issues in the re-search designs.It was found the issues in common consisted of five aspects:research background,types of design,inclusion and exclusion criteria,outcomes,and sample size.Meanwhile,the causes of these problems were discussed and the countermeasures were proposed aimed at improving the efficiency of scientific review work and promoting the high-quality operation of IIT projects.

Content determination of seventeen amino acids in Gualoupi Injection and its intermediates and research on their change laws / 中成药

AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4％-119.5％with the RSDs of 0.91％-7.94％.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.

Efficacy of arthroscopic double-row double-pulley technique in the treatment of Ideberg type IA scapular glenoid fracture / 中华创伤杂志

Objective:To investigate the clinical efficacy of arthroscopic double-row double-pulley technique in the treatment of Ideberg type IA scapular glenoid fracture.Methods:A retrospective case series study was conducted to analyze the clinical data of 16 patients with Ideberg type IA scapular glenoid fracture admitted to Jiading Branch of Shanghai General Hospital from January 2018 to December 2021, including 10 males and 6 females, aged 25-65 years [(42.9±5.1)years]. The patients were treated with arthroscope-assisted reduction and double-row double-pulley technique. The operation time was recorded. Three-dimensional reconstruction of the shoulder joint with CT was performed to assess fracture displacement and healing. Modified University of California Los Angeles (UCLA) score and Constant-Murley score were used to evaluate shoulder function and Visual Analogue Scale (VAS) score was used to evaluate pain before surgery, at 3, 6, 12 months after surgery and at the last follow-up. The complications were observed.Results:All the patients were followed up for 12-36 months [(20.3±4.4)months]. The operation time was 60-90 minutes [(74.7±8.9)minutes]. Three-dimensional construction of the shoulder joint with CT performed at 3 months after surgery showed that there was no fracture re-displacement and all the patients had bone union. The modified UCLA score, Constant-Murley score and VAS score at 3 months after surgery were (30.4±0.4)points, (84.3±1.4)points and 2.0(1.3, 3.0)points, respectively, which were significantly improved compared with those before surgery [(21.1±0.5)points, (56.4±1.3)points and 5.0(5.0, 6.0)points respectively] ( P<0.05). The modified UCLA score, Constant-Murley score and VAS score at 6 months after surgery were (33.1±0.4)points, (91.0±0.5)points and 1.0(1.0, 2.0)]points respectively, which were significantly improved compared with those at 3 months after surgery ( P<0.05). The modified UCLA score, Constant-Murley score and VAS score at 12 months after surgery were (33.5±0.3)points, (92.6±0.6)points and 1.0(0.3, 1.8)points respectively, showing no significant differences from those at 6 months after surgery ( P>0.05). The modified UCLA score, Constant-Murley score and VAS score at the last follow-up were (33.8±0.8)points, (93.7±1.8)points and 1.0(0.0, 1.0)points respectively, with no significant differences from those at 12 months after surgery ( P>0.05). There were no complications such as wound infection, neurovascular injury or shoulder stiffness after surgery. Conclusion:Arthroscopic double-row double-pulley technique for the treatment of Ideberg type IA scapular glenoid fracture has a short operation time, a high fracture healing rate, good shoulder function recovery, and pain relief, with no common complications.

Simultaneously quantitative analysis of 35 components in gualoupi injection using hydrophilic interaction liquid chromatography tandem mass spectrometry / 药学学报

A hydrophilic interaction chromatography tandem mass spectrometry method was developed for simultaneous quantification of 35 components in gualoupi injection. The analytes were separated with an ACQUITY XBridge Amide column using 20 mmol·L-1 ammonium formate aqueous solution (pH 3.0) as mobile phase A and 20 mmol·L-1 ammonium formate (pH 3.0)∶acetonitrile (1∶9) as mobile phase B for gradient elution. Mass spectrometry with dynamic multiple reaction monitoring and external standard method were used for quantitative analysis. A total of 35 components were determined in 10 batches of gualoupi injection. The results showed that the 35 compounds had a good linear relationship within their respective concentration ranges with the correlation coefficients (R2 > 0.998 0), the recoveries ranged from 76.6% to 118.5%. The results showed that γ-aminobutyric acid, trigonelline, alanine, threonine, homoserine, citrulline, and leucine were abundant in gualoupi injection, while nicotinamide, methylsuccinic acid, cytosine and choline account for a low percentege. The present study provides an important reference for elucidation of the effective material basis and the improvement of quality standard of gualoupi injection.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Short-term efficacy of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective:To investigate the clinical effect and safety of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 24 patients with stage Ⅲ-IV A NPC were recruited prospectively to receive two cycles of camrelizumab combined with induction chemotherapy (docetaxel 75 mg/m 2+ cisplatin 25 mg/m 2 for three consecutive days) followed by concurrent chemoradiotherapy (prescription doses: 6 996 cGy in 33 fractions for PGTV and PGTV nd, 6 006 cGy in 33 fractions for PTV 1, 5 096 cGy in 28 fractions for PTV 2, and concurrent cisplatin chemotherapy with a dose of 75 mg/m 2). The short-term efficacy and adverse reactions were evaluated. Results:After induction therapy, nasopharyngeal lesions showed an objective response rate (ORR) of 91.6%, including 45.8% of complete response (CR) and 45.8% of partial response (PR); cervical lymph nodes showed an ORR of 95.8% (CR: 4.2%; PR: 91.6%). Seventeen patients accepted a reexamination under a nasopharyngoscope, and the biting biopsy result indicated that 13 patients among them had complete pathologic response. After concurrent chemoradiotherapy, nasopharyngeal lesions and cervical lymph nodes showed CR rates of 83.3% and 91.7% and PR rates of 16.7% and 8.3%, respectively. After the induction therapy, 13 patients with stage IV A NPC had ORR (PR) rates of 92.4% and 92.4%, respectively, at nasopharyngeal lesions and cervical lymph nodes. After concurrent chemoradiotherapy, the patients with stage IV A NPC had CR rates of 84.6% and 92.3% and PR rates of 15.4% and 7.7%, respectively, at nasopharyngeal lesions and cervical lymph nodes. Major adverse reactions include leukopenia, granulopenia, anemia, radioactive acute oropharyngeal mucositis and dermatitis, digestive tract reaction, fatigue, hypothyroidism, aminotransferase elevation, and reactive capillary hyperplasia. Conclusions:Camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy can achieve high short-term efficacy for patients with locally advanced nasopharyngeal carcinoma, without increasing the incidence of adverse reactions. Its long-term efficacy deserves further research.

Neutrophil-lymphocyte and platelet-lymphocyte ratios for assessing disease activity in patients with rheumatoid arthritis receiving tofacitinib treatment / 南方医科大学学报

OBJECTIVE@#To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib.@*METHODS@#This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity.@*RESULTS@#PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients.@*CONCLUSION@#NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.

Predictive value of hepatic fibrosis-4 index for early neurological deterioration in patients with ischemic stroke after intravenous thrombolysis / 国际脑血管病杂志

Objective:To investigate the correlation between the degree of hepatic fibrosis and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS) and its predictive value.Methods:Patients with AIS received intravenous thrombolysis at Nanjing Jiangbei Hospital from January 2018 to March 2023 were retrospectively included. Hepatic fibrosis-4 index (FIB-4) was used to evaluate the degree of hepatic fibrosis in patients. FIB-4 ≥ 2.67 was defined as severe hepatic fibrosis. END was defined as an increase of ≥4 from baseline on the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after intravenous thrombolysis. The relevant factors of END were analyzed through univariate analysis and multivariate logistic regression model. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of FIB-4 for END. Results:A total of 313 patients were included, of which 184 (58.8%) were male, aged 64.8±11.8 years old. The median baseline NIHSS score was 6 (interquartile range, 4-9), and the median FIB-4 was 1.76 (interquartile range, 1.28-2.56). Forty-five patients (14.4%) experienced END. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, higher FIB-4 was significantly independently correlated with END (odds ratio 2.121, 95% confidence interval 1.422-3.162; P=0.001). ROC curve analysis shows that FIB-4 has a good predictive value for END (the area under the curve 0.689, 95% confidence interval 0.595-0.784; P=0.001). The optimal cutoff value of FIB-4 was 1.82, and its sensitivity and specificity in predicting END were 71.1% and 54.9%, respectively. Conclusion:FIB-4 has good predictive value for END in patients with AIS after intravenous thrombolysis.

Association between neurotransmitters and dyskinesia in patients with vascular Parkinson syndrome and the predictive value of neurotransmitters / 中风与神经疾病杂志

@#Objective To investigate the association between neurotransmitters and dyskinesia in patients with vascular Parkinson syndrome(VPS) and the predictive value of neurotransmitters. Methods A retrospective analysis was performed for 60 patients with VPS who were hospitalized in Department of Neurology in our hospital from December 2020 to December 2022,and they were enrolled as observation group;60 patients with Parkinson disease who were hospitalized in our hospital during the same period of time were enrolled as control group;60 patients who underwent physical examination in the Physical Examination Center of our hospital during the same period of time were enrolled as healthy group. The simplified Fugl-Meyer Assessment(FMA) score was used to evaluate the motor function of patients. The above three groups were compared in terms of serum neurotransmitters[5-hydroxytryptamine(5-HT),dopamine(DA)] and FMA score;the VPS patients with different Hoehn-Yahr stages were compared in terms of serum neurotransmitters and FMA score;the VPS patients with different severities of dyskinesia were compared in terms of serum neurotransmitters. A Pearson correlation analysis was used to investigate the correlation of serum 5-HT and DA with FMA score;the receiver operating characteristic(ROC) curve was plotted and the area under the ROC curve(AUC) was calculated to analyze the efficacy of 5-HT and DA in predicting dyskinesia. Results The observation group had significantly lower serum 5-HT and DA and FMA score than the control group and the healthy group(P<0.05),and the control group had significantly lower serum 5-HT and DA and FMA score than the healthy group(P<0.05). The stage Ⅳ group had significantly lower serum 5-HT and DA and FMA score than the stage Ⅲ group,and the stage Ⅲ group had significantly lower serum 5-HT and DA and FMA score than the stage Ⅱ group(P<0.05). The severe dyskinesia group had significantly lower serum 5-HT and DA than the obvious dyskinesia group(P<0.05),the obvious dyskinesia group had significantly lower serum 5-HT and DA than the moderate dyskinesia group(P<0.05),and the moderate dyskinesia group had significantly lower serum 5-HT and DA than the mild dyskinesia group(P<0.05). Serum 5-HT and DA were positively correlated with FMA score(r=0.411 and 0.403,P<0.05). The combined measurement of 5-HT and DA had an AUC of 0.803(95% CI 0.713-0.938) in predicting dyskinesia,with higher sensitivity and specificity than the measurement of each index alone(sensitivity:92.72% vs 75.27%/72.87%,P<0.05;specificity:90.83% vs. 72.64%/70.09%,P<0.05). Conclusion Dyskinesia in VPS patients is closely associated with the abnormally low expression of serum 5-HT and DA,both of which are involved in dyskinesia. The combined measurement of serum 5-HT and DA can improve the predictive efficacy of dyskinesia and thus has a certain reference value.

Deep brain stimulation in patients with Parkinson's disease at Hoehn-Yahr stage 2.5-5: a single-center long-term follow-up study / 中华神经医学杂志

Objective:To investigate the long-term clinical effect of deep brain stimulation (DBS) on patients with Parkinson's disease (PD) at Hoehn-Yahr stage 2.5-5 and the differences of clinical effect among patients at different Hoehn-Yahr stages.Methods:A total of 69 PD patients (7 at Hoehn-Yahr stage 2.5, 27 at stage 3, 31 at stage 4, and 4 at stage 5) accepted DBS in Department of Functional Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University from May 2014 to December 2016 were selected for long-term follow-up observation at 60 months after DBS. Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated in the "off" phase of the patients before DBS and the "off" phases of the drugs under DBS start-up and continuous treatment at 6, 12, 24, 36, 48 and 60 months after DBS, respectively; Parkinson's Quality of Life Questionnaire (PDQ-39) and levodopa equivalent dose (LED) data were collected before and 6, 12, 24, 36, 48 and 60 months after DBS. DBS parameters of the patients were collected at 12 months after DBS; the total stimulation power, single pulse average energy and large single pulse energy were calculated. The differences in UPDRS-III scores, PDQ-39 scores and LEDD in these patients before DBS and at different time points after DBS were compared; the differences in UPDRS-III and PDQ-39 scores at different time points after DBS and postoperative DBS parameters at 12 months after DBS in patients at different Hoehn-Yahr stages were compared.Results:Compared with those before DBS, the UPDRS-III scores, PDQ-39 scores and LED were significantly reduced at 6, 12, 24, 36, 48 and 60 months after DBS ( P<0.05). Significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 2.5 and stage 3 at 12 and 24 months after DBS ( P<0.05); however, no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 4 at same time points ( P>0.05); and no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and patients at Hoehn-Yahr stage 2.5, stage 3, and stage 4 at other time points ( P>0.05). No significant differences in PDQ-39 scores were noted between patients at different Hoehn-Yahr stages at 6, 12, 24, 36, 48, and 60 months after DBS ( P>0.05). No significant difference in total stimulation power, single pulse average energy or large single pulse energy was noted among patients at different Hoehn-Yahr stages at 12 months after DBS ( P>0.05). Conclusion:DBS is long-term effective in improving motor function and quality of life in PD patients at Hoehn-Yahr stage 2.5-5, and patients at Hoehn-Yahr stage 5 do not need higher DBS parameters to obtain similar clinical improved effects as patients at Hoehn-Yahr stage 2.5-4.

Research progress of effective components of Astragalus on prevention and treatment of organ fibrosis / 药学学报

Astragalus, which was first documented in Shennong Bencao Jing, is the dried root of Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. The active ingredients astragalus membranaceus saponins (AMS), astragalus polysaccharides (APS) and astragalus flavonoids (AFS) have pharmacological effects such as anti-tumor properties, lowering blood sugar, regulating lipid metabolism, cardiovascular protection, anti-oxidation, bone protection, anti-fibrosis, etc. Fibrosis affects almost all organs, particularly vital organs such as the lungs, liver, heart and kidneys. The primary pathological changes of fibrosis involve abnormal increase of myofibroblasts and excessive deposition of extracellular matrix (ECM) components, which lead to the formation of scar tissue, ultimately resulting in fibrosis and even functional loss or failure of organs, which seriously threatens human health and life. Recent, studies have shown that Astragalus membranaceus has a good therapetuic effect on organ fibrosis. This article reviews the current advances of Astragalus in the prevention and treatment of fibrosis of lungs, liver, heart, kidneys and other important organs.

The prognostic and predictive value of plasma D-dimer in children with neuroblastoma: a 7-year retrospective analysis at a single institution

Purpose@#Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. @*Methods@#A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020.Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. @*Results@#Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. @*Conclusion@#A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.

Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Plasma components of Danzhi Xiaoyao Formula and its mechanism of action in treating perimenopausal depression based on UPLC-Q-TOF-MS~E integrated with network pharmacology / 中国中药杂志

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice.@*METHODS@#The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively.@*RESULTS@#The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs.@*CONCLUSION@#PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Mechanism of lncRNA NEAT1 promoting hepatocyte injury and inflammatory reaction induced by sepsis / 局解手术学杂志

Objective To explore the mechanism of hepatocyte injury and inflammatory reaction induced by sepsis based on miR-129-5p/TLR4 signaling axis regulated by lncRNA NEAT1.Methods Peripheral blood from 15 sepsis patients(the sepsis group)and 15 healthy individuals(the healthy group)were collected for gene expression detection.The mouse normal liver cell line NCTC1469 was used in in vitro experiments,and an in vitro sepsis model(the LPS group)was established by lipopolysaccharide(LPS).The cells stimulated with LPS and transfected with mimic NC,mimic,siNC or siNEAT1 plasmid vectors were named as the LPS+mimic NC group,the LPS+mimic group,the LPS+siNC group or the LPS+siNEAT1 group,respectively.The cells treated with a combination of LPS,siNEAT1,and TLR4 recombinant protein or LPS,mimic,TLR4 recombinant protein were named as the LPS+siNEAT1+TLR4 group or the LPS+mimic+TLR4 group,while the control group was not treated.The mRNA and protein expression levels of TNF-α,IL-6,and IL-1β were detected by qPCR and ELISA,respectively.The cell apoptosis rate was detected by TUNEL assay.The binding of lncRNA NEAT1/miR-129-5p and miR-129-5p/TLR4 was detected by dual-luciferase reporter gene analysis.The TLR4 expression in cells was detected by Western blot.Results In the in vivo experi-ment,compared with the healthy group,the expression of TNF-α,IL-6,IL-1β,lncRNA NEAT1,and TLR4 of peripheral blood in the sepsis group was significantly increased(P<0.05),while the expression of miR-129-5p was decreased(P<0.05).In the in vitro experiment,compared with the control group,the expression of lncRNA NEAT1 in the LPS group was increased(P<0.05).Compared with the LPS group and the LPS+siNC group,the expression of lncRNA NEAT1 in the LPS+siNEAT1 group was decreased(P<0.05),and the expression of miR-129-5p was increased(P<0.05).Compared with the control group,the cell apoptosis rate and the expression of TLR4,TNF-α,IL-6,and IL-1β in the LPS+siNC group were up-regulated(P<0.05).Compared with the LPS+siNC group,the cell apoptosis rate and the expression of TLR4,TNF-α,IL-6,and IL-1β in the LPS+siNEAT1 group were down-regulated(P<0.05).Compared with the LPS+siNEAT1 group,the cell apoptosis rate and the expression of TLR4,TNF-α,IL-6,and IL-1β in the LPS+siNEAT1+TLR4 group were up-regulated(P<0.05).Dual-luciferase reporter gene assay revealed an interaction between lncRNA NEAT1 and miR-129-5p,and TLR4 was the target gene of miR-129-5p.Compared with the control group,the expression of TNF-α,IL-6,and IL-1β as well as cell apoptosis rate in the LPS+ mimic NC group were increased(P<0.05).Compared with the LPS+mimic NC group,the expression of TNF-α,IL-6,and IL-1β as well as cell apoptosis rate in the LPS+mimic group were down-regulated(P<0.05).Compared with the LPS+mimic group,the expression of TNF-α,IL-6,and IL-1β as well as cell apoptosis rate in the LPS+mimic+TLR4 group were up-regulated(P<0.05).Conclusion lncRNA NEAT1 interacts with miR-129-5p and directly targets TLR4 to promote LPS-induced hepatocyte injury and inflammatory reaction.This study can provide a new therapeutic target for hepatocyte injury caused by sepsis.

A novel device for cannulated screwing for femoral neck fracture / 中华创伤骨科杂志

Objective:To evaluate our self-designed novel guide device for cannulated screwing in the treatment of femoral neck fracture.Methods:Between June 2019 and July 2020, 40 patients with femoral neck fracture were treated with cannulated screwing at Department of Orthopaedics, The Second Hospital Affiliated to Shanxi Medical University. They were divided into a manual group of 20 cases whose cannulated screwing was implemented by hand and a guide group of 20 cases whose cannulated screwing was implemented with the aid of our self-designed guide device. In the guide group, there were 5 males and 15 females, with an age of (48.4±10.2) years (from 18 to 63 years); there were 12 cases of types Ⅰ & Ⅱ and 8 cases of types Ⅲ & Ⅳ by the Garden classification. In the manual group, there were 8 males and 12 females, with an age of (49.8±8.4) years (from 18 to 60 years); there were 13 cases of types Ⅰ & Ⅱ and 7 cases of types Ⅲ & Ⅳ by the Garden classification. All fractures underwent closed reduction and internal fixation with 3 cannulated screws. The intraoperative fluoroscopy, operation time, femoral cortex drilling, angle between the guide pin and the femoral neck axis in the anteroposterior view, angle between the guide pin and the femoral neck axis in the lateral view, fracture healing time, Harris hip score and complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). In the guide group, intraoperative fluoroscopy [(10.0±2.2) times], operation time [(41.8±5.6) min], femoral cortex drilling [(4.5±1.1) times], angle between the guide pin and the femoral neck axis in the anteroposterior view (3.0°±0.8°) angle between the guide pin and the femoral neck axis in the lateral view (3.9°±1.0°) and fracture healing time [(6.2±0.5) months] were significantly less or smaller than those in the manual group [(24.8±8.3) times, (60.0±15.3) min, (12.8±2.0) times, 7.2°±1.8°, 7.6°±2.6°, and (7.2±0.5) months] (all P<0.05). There was no significant difference in Harris hip score between the 2 groups ( P>0.05). None of the patients had wound infection, internal fixation displacement, fracture nonunion or screw breakage. Conclusions:Application of our self-designed guide device can shorten operation time, improve accuracy of needle insertion, and reduce drilling attempts in the femoral cortex, making cannulated screwing easier for femoral neck fractures.

Correlation between malnutrition and early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between malnutrition and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with ischemic stroke received intravenous thrombolysis in the Department of Neurology, Nanjing Jiangbei People's Hospital from January 2018 to December 2021 were retrospectively enrolled. Nutritional status was assessed by geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI). END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale score within 24 h after intravenous thrombolysis compared with the baseline value. The demographic and baseline clinical data of the patients in the END group and the non-END group were compared. Multivariate logistic regression analysis was used to determine the independent correlation between malnutrition and END. Results:A total of 256 patients were enrolled, including 156 males (60.9%), aged 65.6±12.0 years. According to GNRI and PNI, there were 122 (46.7%) and 62 (24.2%) patients with malnutrition respectively. END occurred in 37 patients (14.5%) during hospitalization. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, there was a significant independent correlation between malnutrition and END after intravenous thrombolysis in patients with acute ischemic stroke (severe malnutrition as assessed by GNRI compared to normal nutritional status: odds ratio 5.736, 95% confidence interval 1.033-31.866, P=0.046; severe malnutrition as assessed by PNI compared to normal nutritional status: odds ratio 4.928, 95% confidence interval 1.589-15.282, P=0.006). Conclusion:Malnutrition is very common in patients with acute ischemic stroke and has a significant correlation with END after intravenous thrombolysis.

Prognostic value of pre-operation systemic inflammation response index in decompressive craniectomy for massive cerebral infarction caused by middle cerebral artery embolization / 中国综合临床

Objective:To explore the correlation between systemic inflammatory response index (SIRI) and clinical outcome of patients with massive cerebral infarction (MCI) after craniotomy and decompression.Methods:The clinical data of 50 MCI patients who were treated in the Affiliated Hospital of Qingdao University from January 2016 to December 2020 and underwent craniotomy and decompression were retrospectively analyzed. The measurement data of normal distribution were expressed as xˉ± s, and the measurement data of non normal distribution were expressed as M( Q1, Q3). T-test or rank sum test was used for comparison between the two groups. Multivariate Logistic regression was used to analyze the relationship between SIRI and prognosis of MCI patients and establish a prediction model. The predictive value and optimal cutoff value of SIRI were analyzed by receiver operating characteristic curve (ROC). Results:Among the 50 MCI patients who underwent craniotomy and decompression, 12 (24%, 12/50) had a good prognosis; In the poor prognosis group, 38 cases (76%, 12/50), of which 9 cases (18%, 9/50) died during hospitalization. The age of patients in the good prognosis group and the poor prognosis group ((54±11) years and (63±9) years; t=2.72, P=0.015), body mass index (BMI): ((23.91±2.64) kg/m 2 and (26.72±3.28) kg/m 2, t=3.01, P=0.006)), neutrophil count (7.08 (5.12, 7.38))×10 9/L and 10.59 (8.91,14.64)×10 9/L, Z=5.72, P<0.001), white blood cell count ((9.09±2.80)×10 9/L and (13.20±3.49) ×10 9/L; t=4.16, P<0.001), SIRI (2.49(1.78, 4.75) and 8.34(5.17, 13.61); Z=3.84, P<0.001), Glasgow Coma Score (12(9,14) and 8(6,10); Z=3.36, P=0.002) and lymphocyte count (1.58(0.91, 1.91)×10 9/L and 0.77(0.59,1.02) ×10 9/L; Z=3.30, P=0.001).The difference between the two groups was statistically significant. The prognosis of patients with dominant hemisphere infarction was worse than that of patients with non-dominant hemisphere infarction (22 cases (91.67%, 22/24) vs. 16 cases (61.54%, 16/26); χ 2=6.21, P=0.013). The ICU stay in the good prognosis group was significantly shorter than that in the poor prognosis group (2 (1, 5) days vs. 8 (3, 19) days; Z=2.78, P=0.005). Multivariate Logistic regression analysis showed that SIRI and GCS were correlated with clinical prognosis: SIRI ( OR: 2.378; 95% CI: 1.131-5.003; P=0.022); GCS at admission ( OR: 0.548; 95% CI: 0.307-0.980; P=0.043). The ROC curve analysis of SIRI prediction of poor prognosis: Area under the curve (AUC): 0.871, (95% CI: 0.765-0.976, P<0.001), sensitivity was 78.9%, specificity was 88.3%, and the optimal cut-off value was 4.96. The sensitivity, specificity and AUC of GCS for predicting poor prognosis after MCI craniotomy decompression were 89.5%, 58.3% and 0.791 (95% CI: 0.638~0.943, P=0.003), and the best truncation value was 11.5. Conclusion:SIRI was an effective predictor of clinical outcome for MCI patients underwent Craniotomy for decompression, and SIRI value greater than 4.96 indicates adverse clinical outcome.