Three-dimensional evaluation of the mandibular condyle in adults with various skeletal patterns / 대한치과교정학회지

Objective@#Morphometric and morphological evaluation of the mandibular condyle in adults and to identify its correlation with skeletal malocclusion patterns. @*Methods@#Cone-beam computed tomography scans of 135 adult patients were used in this study and classified into groups according to four criteria: (1) sex (male and female); (2) sagittal skeletal discrepancy (Class I, Class II, and Class III); (3) vertical skeletal discrepancy (hyperdivergent, normodivergent, and hypodivergent); and age (group 1 ≤ 20 years, 21 ≤ group 2 < 30, and group 3 ≥ 30 years). The morphometrical variables were mandibular condyle height and width, and the morphological variable was the mandibular condyle shape in coronal and sagittal sections. Three-dimensional standard tessellation language files were created using itk-snap (open-source software), and measurements were performed using Meshmixer (open-source software). @*Results@#The mandibular condyle height was significantly greater (p < 0.05) in patients with class III malocclusion than in those with class I or II malocclusion;the mandibular condyle width was not significantly different among different sexes, age groups, and sagittal and vertical malocclusions. There were no statistical associations between various mandibular condyle shapes and the sexes, age groups, and skeletal malocclusions. @*Conclusions@#The condylar height was greatest in patients with class III malocclusion. The condylar height and width were greater among males than in females. The mandibular condyle shapes observed in sagittal and coronal sections did not affect the skeletal malocclusion patterns.

Systematic evaluation of pharmacoeconomic studies on acute ischemic stroke population in China / 中国药房

OBJECTIVE To systematically evaluate pharmacoeconomic studies （modeling approach） based on the Chinese acute ischemic stroke （AIS） population， and to provide the suggestions for improving the pharmacoeconomic evaluation method of AIS. METHODS Retrieved from CNKI， Wanfang Data Knowledge Service Platform， VIP， PubMed， Embase， the Cochrane Library， ScienceDirect， and Web of Science databases， relevant literature on pharmacoeconomic evaluation of AIS were collected from January 2014 to February 2022. Basic information of included study， basic information and outcome indicators of the model were analyzed statistically. The quality of the included literature was evaluated using CHEERS 2022， and problems in the existing literature were identified and suggestions were made. RESULTS Twelve papers were finally included， involving five in Chinese and seven in English. All studies reported the study perspective， mainly from the perspective of health system； the age of the target population was mainly distributed around 60 years old； the main interventions in the included studies were pharmacotherapy， including single-drug regimens and combination drug regimens； nine papers used decision trees combined with Markov models， and three papers used Markov models alone， but the classification of health status was inconsistent； all papers reported study time frame and cycle period， with most studies choosing a study time frame of 30 years and a cycle period of 1 year； all studies used modified Rankin scale scores as an indicator of clinical effectiveness， which were mainly derived from clinical trials； utility values in most literature were derived from published studies， and costs were mainly direct medical costs； all studies performed cost-utility analyses using quality-adjusted life years and/or incremental cost-effectiveness ratios as outcome indicators， and single-factor sensitivity analyses and probabilistic sensitivity analyses were performed， but no contextual analyses were conducted for the different model structures that may exist. CONCLUSIONS The overall report of the included studies is relatively complete， but the methodology is relatively uniform， and there are still deficiencies in terms of study perspective， study time frame， parameter sources， and contextual analysis. Future AIS pharmacoeconomic evaluations should further improve the report content in accordance with the CHEERS list entries， conduct contextual analysis of multiple health state classification approaches from a society-wide perspective， while using data from real- world sources and standardizing the uncertainty analysis process of the study results to increase the authenticity and reliability of the study results.

Autophagy-regulated strategies in pre-clinical studies of inflammatory bowel disease / 药学学报

Inflammatory bowel disease (IBD) is a group of chronic idiopathic colorectal inflammatory diseases with a progressive and unpredictable course, including ulcerative colitis (UC) and Crohn's disease (CD). Abnormal intestinal inflammation and immune response contribute to the pathogenesis of IBD. Autophagy as an essential catabolic process in cells, has been demonstrated to have associations with a variety of inflammatory diseases including IBD. Here, we review the relationship between autophagy dysfunction and the process of IBD. The progress of several autophagy regulators for intestinal epithelial cells and macrophages is highlighted (inflammasome inhibitors, intestinal flora regulators, and other signal regulators) in the current studies on IBD.

miR-3607-3p inhibits the malignant biological behavior of cervical cancer cells by mediating the expression of profilin 2 / 中国医师杂志

Objective:To explore the effect of miR-3607-3p on the malignant phenotype of cervical cancer cells and related mechanisms.Methods:The OncoLnc bioinformatics website was used to analyze the relationship between the expression of miR-3607-3p and the prognosis of cervical cancer patients. Real time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-3607-3p in human normal cervical epithelial cells (H8) and cervical cancer cell lines (Hela, HCC94, SiHa, C33A). SiHa cells transfected with negative control nucleotide sequence in vitro were defined as negative control (NC) group, and SiHa cells transfected with miR-3607-3p mimicked sequence was defined as miR-3607-3p group. qRT-PCR was used to detect the expression changes of miR-3607-3p in SiHa cells. Cell counting kit-8 (CCK-8) method and scratch test were used to detect the malignant biological behavior changes of SiHa cells. qRT-PCR and Western blot were used to detect the expression changes of profilin 2 (PFN2) gene, and the dual luciferase reporter gene experiment was used to detect the targeting relationship between miR-3607-3p and PFN2. Results:The survival time of patients with high expression of miR-3607-3p was significantly higher than that of patients with low expression of miR-3607-3p ( P<0.01). Compared with H8 cells, the expression of miR-3607-3p was abnormally low in human cervical cancer cell lines ( P<0.05), and the expression of miR-3607-3p was the lowest in the SiHa cell line ( P<0.01). The expression of miR-3607-3p in the NC group and miR-3607-3p group was (1.04±0.31) and (9.28±1.76), respectively. The expression level of miR-3607-3p in SiHa cells transfected with miR-3607-3p mimic sequence was significantly higher than that in NC group, and the proliferation activity and scratch healing rate were significantly lower than that in NC group (all P<0.01). Dual-luciferase reporter gene assay confirmed that miR-3607-3p directly targeted and binded to PFN2 ( P<0.01). qRT-PCR and Western blot results showed that the expression of PFN2 mRNA and protein in miR-3607-3p group was lower than that in NC group; Western blot results showed the expression of proliferating proteins CDK3 and CDK2 in miR-3607-3p group was lower than that in NC group (all P<0.05), and the expression of epithelial phenotype related proteins Claudin-1 and ZO-1 in miR-3607-3p group was higher than that in NC group (all P<0.05). Conclusions:miR-3607-3p is positively correlated with the survival of cervical cancer patients. Up-regulating the expression of miR-3607-3p can inhibit the proliferation and migration of cervical cancer SiHa cells. The mechanism may be related to the targeted inhibition of PFN2.

Application value of contrast-enhanced ultrasound before and after microwave ablation of thyroid nodules / 中国基层医药

Objective:To investigate the application value of contrast-enhanced ultrasound (CEUS) before and after microwave ablation of thyroid nodules.Methods:Fifty-six patients (79 thyroid nodules) who received microwave ablation of thyroid nodules in Huaian Medical District, General Hospital of Eastern Theater Command from March 2016 to October 2019 were included in this study. CEUS was performed before microwave ablation to accurately assess the size, number and blood supply of thyroid nodules as well as the position of the feeding vessels. CEUS was performed immediately after microwave ablation to determine whether the lesion area was thoroughly ablated and to measure the volume of thyroid nodules. At 1, 3, 6 and 12 months after surgery, the level of thyroid hormone was measured and the absorption of thyroid nodules was evaluated.Results:Preoperative CEUS showed that among the 79 thyroid nodules, 42 were solid nodules that had different degrees of enhancement, including 33 annular homogeneously highly enhanced nodules and 9 heterogeneously highly enhanced nodules; 24 were cystic mixed solid nodules that had solid components, including 16 homogeneously highly enhanced nodules and 8 nodules with only local high enhancement in the solid component; 13 were cystic nodules, including 9 nodules with septa and 3 nodules with contrast medium on the diaphragm. Contrast medium was still visible around three nodules immediately after microwave ablation. Ablation continued in three nodules until there was no contrast medium. The incidence of complications during and after treatment was 0%. The average volume of the thyroid nodules before treatment was (7.52 ± 6.74) cm3. At 1, 3, 6 and 12 months after surgery, the average volume of the thyroid nodules was (6.06 ± 5.19) cm3, (3.06 ± 2.85) cm3, (1.32 ± 1.23) cm3 and (0.59 ± 0.52) cm 3, respectively. There was significant difference in volume of thyroid nodules between before and after microwave ablation ( F = 96.32, P < 0.001). Conclusion:Preoperative CEUS can determine the distribution of the blood supply of thyroid nodules and the course of the feeding vessels, identify the needle-entering position for microwave ablation and the primary ablation area, improve the accuracy of treatment, and reduce the occurrence of complications such as bleeding. Postoperative CEUS can determine whether lesion area is thoroughly ablated, reduce residual lesions and excessive ablation.

Summary of best evidence for exercise rehabilitation for atrial fibrillation / 中国实用护理杂志

Objective:To evaluate and summarize the best evidence of exercise instructions for patients with atrial fibrillation.Methods:A comprehensive search about evidence on exercise rehabilitation in patients with atrial fibrillation was conducted in following databases: Joanna Briggs Institute (JBI) Library, The Agency for Healthcare Research and Quality (AHRQ), National Institute for Health and Clinic Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), Registered Nurses′ Association of Ontario (RNAO), Physiotherapy Evidence Database (PEDro), American College of Physicians (ACP), Cochrane Library, PubMed, Embase, CINAHL, Medlive, China National Knowledge Infrastructure (CNKI), WanFang Database, VIP Database, and China Biology Medicine (CBM). The retrieval period was from the inception of databases to January 2021. Two researchers with evidence-based nursing background assessed the quality of the literature independently and identified the level of evidence.Results:A total of 16 articles were included, including 4 guidelines, 4 systematic reviews, 4 expert consensuses, 4 randomized controlled trials. Combined with professional judgment, 35 pieces of best evidence in 7 aspects were summarized, including exercise benefits, the appropriate crowd, exercise evaluation, exercise mode, exercise intensity, exercise time, exercise supervision and safety.Conclusions:Regular exercise is safe and beneficial for patients with atrial fibrillation. Clinical staff should guide patients to exercise moderately by applying the best evidence with scientific exercise intervention, promoting patients′ physical and mental health.

Early recovery status and outcomes after sepsis-associated acute kidney injury in critically ill patients / 中南大学学报(医学版)

Objective:Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients ' quality of life.Methods:We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease:Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients ' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3.Results:A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4％), 73 (13.2％), and 229 (41.4％) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2％ vs 26.0％ or 22.7％; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery:65.1％vs 27.4％or 22.7％;P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95％ CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95％CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate>20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. Conclusion:The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.

Application progress of single cell sequencing technology in diagnosis of genetic and reproductive / 国际生物医学工程杂志

The technique of prenatal diagnosis before embryo implantation has been greatly developed in assisted reproduction, especially for the people with abnormal genetic material to provide the technical possibility of eugenics and eugenics. As an emerging sequencing technology, single-cell sequencing can analyze the genome and transcriptome of cells from the level of a single cell, and reflect the heterogeneity between cells, thus helping to reveal the mechanism of the occurrence and development of diseases. Through prenatal diagnosis before embryo implantation and high-throughput sequencing of single cells obtained from embryo biopsy, euploidy of embryonic chromosomes can be effectively detected, and SNPs and chromosomal copy number variation, insertion, deletion and other variations can also be better detected. It can conduct the comprehensive detection and research of genomic polymorphism and mutation of individual and other species. In this paper, the single-cell sequencing technology and relevant methods was introduced, and the application scenarios of single-cell sequencing in genetic reproduction diagnosis were summarized. The applications of the technology in the field of genetic reproduction were described, and the future directions of the technology were discussed.

Evaluation value of intravascular optical coherence tomography for carotid atherosclerotic plaques / 国际脑血管病杂志

Objective:To investigate the evaluation value of optical coherence tomography (OCT) for carotid atherosclerotic plaques.Methods:Patients with carotid atherosclerotic stenosis underwent digital subtraction angiography (DSA) and OCT in the Affiliated Hospital of Jining Medical College from January 2020 to January 2022 were retrospectively enrolled. The demographics, baseline clinical data, DSA and OCT imaging data of the symptomatic group and the asymptomatic group were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for symptomatic carotid atherosclerotic stenosis. Results:A total of 39 patients were enrollded, including 21 in the symptomatic group and 18 in the asymptomatic group. The detection rate of fibrous plaque in the symptomatic group was significantly lower than that in the asymptomatic group (38.1% vs. 77.78%; P=0.023), while the detection rate of plaque rupture (38.1% vs. 5.56%; P=0.023) and macrophage infiltration (42.86% vs. 11.11%; P=0.037) was significantly higher than that in the asymptomatic group. Multivariate logistic regression analysis showed that plaque rupture (odds ratio 6.982, 95% confidence interval 1.068-45.660; P=0.043) and macrophage infiltration (odds ratio 6.480, 95% confidence interval 1.009-41.625; P=0.049) were significantly independently associated with the symptomatic carotid atherosclerotic stenosis. Conclusions:OCT is of value in evaluating the plaque characteristics of carotid atherosclerotic stenosis. Plaque rupture and macrophage infiltration are the independent risk factors for symptomatic carotid atherosclerotic stenosis.

Study on influencing factors of plasma FDP and D-dimer levels of newborns in NICU / 国际儿科学杂志

Objective:To investigate the influencing factors of physiological and pathological conditions at birth of newborn and gestational conditions of pregnant mothers on plasma fibrin/fibrinogen degradation products(FDP)and D-dimer levels.Methods:From May 1, 2018 to October 31, 2018, 222 newborns admitted to NICU of the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were enrolled in this study.Newborns were sent to NICU within 2 hours after birth and venous blood was collected immediately.The levels of FDP and D-dimer were detected by immunoturbidimetry.Groups were divided according to different gender, gestational age, birth weight, relationship between gestational age and birth weight, mode of delivery, asphyxia at birth, acidosis, antenatal hormone use, anticoagulant drugs, and perinatal risk factors(gestational hypertension, premature rupture of membranes, abnormal placenta, gestational diabetes). The levels of plasma FDP and D-dimer were compared among the groups.Mann Whitney U test, Kruskal Wallis H test, Spearman rank correlation and generalized linear model were used for statistical analysis. Results:The plasma FDP and D-dimer values of 222 NICU neonates were skewed at birth, with median values of 6.00 mg/L and 1.74 mg/L, and quartile distances of 10.40 mg/L and 2.55 mg/L, respectively.The concentrations of FDP in neonates born to natural labour and cesarean section were 11.70 mg/L and 5.30 mg/L, respectively, and D-dimer concentrations were 2.92 mg/L and 1.52 mg/L, respectively.The FDP and D-dimer levels were significantly higher in the former(Z values were -4.006 and -4.198, respectively, P<0.05). The levels of FDP and D-dimer in newborns with different gestational age, different birth weight and different blood pH values were compared respectively, and the differences were statistically significant( χ2 values were 15.322, 18.394, 9.677, 11.492, 7.023 and 8.345, respectively, P<0.05). Further analysis showed that the levels of FDP and D-dimer in neonates with gestational age < 34 weeks were significantly higher than those in~<37 weeks group and ≥37 weeks group( P<0.05). The FDP and D-dimer levels in the birth weight<1 500 g group were significantly higher than those in~<2 500 g group and ≥2 500 g group( P<0.05). Higher FDP and D-dimer levels were found in the pH<7.20 group than in the pH ≥7.35 group( P<0.05). A generalized linear model was established for multifactor analysis.The results showed that the concentration of FDP and D-dimer in plasma was related to gestational age, birth weight and arterial pH value. Conclusion:The levels of plasma FDP and D-dimer in NICU newborns at birth were influenced by gestational age, birth weight and acid-base balance.

The analgesic mechanism of exosomes derived from umbilical cord mesenchymal stem cells in rats modelling osteoarthritis / 中华物理医学与康复杂志

Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.

Interleukin-1β mediates the effect of macrophage androgen receptor on hyperphosphate-induced vascular smooth muscle cell calcification / 中华肾脏病杂志

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

Effective Components of Periploca forrestii Against Rheumatoid Arthritis by Targeting TNF-α / 中国实验方剂学杂志

ObjectiveTo analyze the effective components of Periploca forrestii against rheumatoid arthritis（RA）by targeting tumor necrosis factor （TNF）-α based on network pharmacology and experimental verification. MethodThe preliminary research of the research group found that the alcohol extracts of P. forrestii （CDLF and CQAF） had significant anti-RA activities，and 10 monomers with such activities were identified. The anti-RA activities of active monomers，CDLF， and CQAF were compared by the enzyme-linked immunosorbent assay （ELISA）with interleukin（IL）-6，nitric oxide （NO），IL-1β， and prostaglandin E2（PGE2）as indicators. Network pharmacology was employed to analyze the possible molecular mechanism of P. forrestii against RA. The targeting ability of P. forrestii chemical monomers to TNF-α was verified by TNF-α molecular docking，surface plasmon resonance （SPR）， and TNF-α-induced L929 injury model. ResultELISA showed that the anti-RA activities of CDLF and CQAF were significantly stronger than those of identified 10 active monomers. Network pharmacology analysis showed that the core targets of P. forrestii against RA were signal transducer and activator of transcription protein 3 （STAT3），TNF， and IL-6. Gene Ontology（GO） analysis revealed collagen catabolism，inflammatory response，positive regulation of nuclear factor kappa-B（NF-κB） transcription factor activity，and positive regulation of B cell proliferation. Kyoto Encyclopedia of Genes and Genomes （EKGG） pathway enrichment analysis demonstrated TNF signaling pathway，phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway，NF-κB signaling pathway，Toll-like receptor signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway， etc. Verification experiments by TNF-α molecular docking，SPR， and TNF-α-induced L929 injury model found that CDLF and CQAF had good binding activities and could manifestly antagonize TNF-α. However， the active components separated and identified from CDLF and CQAF did not show the same anti-TNF-α activity. ConclusionThe CDLF and CQAF of P. forrestii may treat RA by targeting TNF-α. The experiments found that the isolated chemical components had weaker binding activity to TNF-α than CDLF and CQAF. Meanwhile，the research group isolated chemical components with a minimum mass fraction of 0.25 ng·g-1 from P. forrestii， which suggested that the active components generated by binding to TNF-α with anti-RA activities were presumedly trace components .

Mechanism of Fuzi Lizhongwan Improving Injury in Cisplatin-induced CIPN Mice by Regulating MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Fuzi Lizhongwan alleviating the damage of chemotherapy-induced peripheral neuropathy （CIPN） mice caused by cisplatin based on mitogen-activated protein kinase （MAPK） signaling pathway. MethodA total of 40 female KM mice were randomized into blank group （distilled water， ig）， model group （distilled water， ig）， Fuzi Lizhongwan group （3.5 g·kg-1， ig）， and aspirin group （0.026 g·kg-1， ig）. Cisplatin （3 mg·kg-1， ip， 5 days） was used to induce CIPN in mice. Administration began while modeling and lasted 12 days. The general conditions and behaviors of mice were observed. After the last administration， samples were collected. Pathological changes of the soles were observed based on hematoxylin-eosin （HE） staining. Biochemical assay was employed to determine the levels of serum superoxide dismutase （SOD）， hydrogen peroxide （H2O2）， malondialdehyde （MDA）， and nitric oxide （NO）， enzyme-linked immunosorbent assay （ELISA） the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and glutathione peroxidase-3 （GPX-3） in kidney tissue， and Western blotting the expression of extracellular signal-regulated kinase1/2 （ERK1/2）， phosphorylated-ERK1/2 （p-ERK1/2）， p38 MAPK， and phosphorylated-p38 MAPK （p-p38 MAPK） in kidney tissue. ResultCompared with the blank group， model group demonstrated obvious pathological damage on the soles， hyperkeratosis of the epidermis with a basketweave pattern， atrophy of stratum spinosum， reduction of cells， and intracellular edema. Compared with the model group， Fuzi Lizhongwan significantly alleviated the pathological damage of the skin tissue of the soles. The model group showed lower body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， higher content of H2O2， MDA， and NO （P<0.01）， and higher expression of IL-6， IL-1β， and TNF-α （P<0.01） than the blank group. Fuzi Lizhongwan group demonstrated higher body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， lower content of H2O2， MDA， and NO （P<0.05）， and lower expression of IL-6， IL-1β， and TNF-α （P<0.01） than the model group. The expression of ERK1/2， p-ERK1/2， p38 MAPK， and p-p38 MAPK increased significantly （P<0.01） in the model group compared with that in the blank group， while the expression decreased significantly （P<0.01） in the Fuzi Lizhongwan group compared with that in the model group. ConclusionFuzi Lizhongwan can relieve the neurological injury of cisplatin-induced CIPN mice and increase the pain threshold of mice， possibly by regulating the MAPK signaling pathway and inhibiting inflammatory response and oxidative stress.

Proteomics Analysis of Mechanism of Shenxiong Glucose Injection in Antagonizing H2O2-Induced Oxidative Damage in H9c2 Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Shenxiong glucose injection （SGI） in inhibiting hydrogen peroxide （H2O2）-induced oxidative damage in H9c2 cells by tandem mass tags （TMT）-labeled quantitative proteomics. MethodH9c2 cells cultured in vitro were exposed to H2O2 for inducing oxidative damage. The cell viability was measured by cell proliferation and cytotoxicity assay （MTS）， followed by peptide fractionation by high performance liquid chromatography （HPLC） and protein expression detection in H9c2 cells by ultrahigh performance liquid chromatography-mass spectrometry. MaxQuant （v1.5.2.8） was utilized for data retrieval， and the high-resolution mass spectrometry was conducted to screen out differentially expressed proteins， which were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The protein expression levels of perilipin 2 （Plin2） and tropomyosin 1 （Tpm1） in cells were measured by Western blot. ResultThe spectral analysis yielded 48 608 specific peptide fragments and 5 903 quantifiable proteins. Compared with the model group，the SGI group exhibited 82 differentially expressed proteins，of which 22 were up-regulated and 60 were down-regulated. GO analysis results showed that the differentially expressed proteins were mainly involved in biological processes such as programmed cell death regulation，regulation of cell proliferation，cardiovascular system development， and cell migration. As revealed by KEGG analysis， these proteins were mainly related to peroxisome proliferator-activated receptor （PPAR），focal adhesion，phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt），and Ras-related protein 1 （Rap1） pathways. Western blot results demonstrated that compared with the model group，SGI significantly increased the Plin2 protein expression and decreased the Tpm1 protein expression （P<0.01），consistent with the proteomics results. ConclusionSGI may inhibit cell apoptosis and antagonize H2O2-induced cell oxidative damage by regulating PPAR，focal adhesion，PI3K/Akt and Rap1 pathways，which should be further verified by subsequent experiments.

A case-control study:the clinical efficacy of total laminectomy with lateral mass screw fixation and single open-door laminoplasty for cervical spinal cord injury without fracture and dislocation / 中国骨伤

OBJECTIVE@#To compare the clinical effects of total laminectomy with lateral mass screw fixation and single open-door laminoplasty in the treatment of cervical spinal cord injury without fracture and dislocation.@*METHODS@#The clinical data of 75 patients with cervical spinal cord injury without fracture and dislocation treated from December 2014 to April 2020 were retrospectively analyzed, including 65 males and 10 females, aged from 33 to 83 years old with an average of (60.1±11.4) years. According to surgical method, the patients were divided into observation group (36 cases) and control group (39 cases). The observation group was treated with C3-C6 single open-door laminoplasty. In the control group, the C3-C6 whole lamina was opened by "uncovering", and the lateral mass screw was fixed and fused. The general conditions including operation time, intraoperative blood loss, hospital stay and complications such as axial pain, cerebrospinal fluid leakage, postoperative C5 nerve palsy were recorded. Visual analogue scale(VAS), Nurick pain scale, Japanese Orthopaedic Association(JOA) scores and American Spinal Injury Association(AISA) injury scale were used to evaluate the improvement of clinical symptoms and related functional recovery 12 months after operation.@*RESULTS@#There were no statistically significant differences in operation time, intraoperative blood loss and hospital stay between two groups(P>0.05). There were statistically significant differences in JOA, VAS, ASIA and Nurick scores of the all patients between 12 months after surgery and before surgery (P<0.05), and there was no significant difference between groups. There was significant difference in the incidence of C5 nerve root palsy and axial pain between two groups(P<0.05), but there was no significant difference in the complications of cerebrospinal fluid leakage between two groups (P>0.05).@*CONCLUSION@#Total laminectomy with lateral mass screw fixation and single open-door laminoplasty in treating cervical spinal cord injury without fracture and dislocation can obtain satisfactory results in restoring nerve function, alleviating pain and improving daily behavior, but single open-door laminoplasty has the advantages of less trauma and low incidence of complications.

Identification, biological characteristics, and fungicide screening of pathogen of black spot in Aconitum carmichaelii / 中国中药杂志

In Hezhang county, Guizhou province, black spot tends to occur to Aconitum carmichaelii in the hot rainy summer, with the incidence up to 50%-70%, seriously impacting the yield and quality of the medicinal material. Thus, this study aims to clarify the pathogen and the occurrence characteristics. To be specific, the pathogen was isolated and identified according to Koch's postulates and the pathogenicity and biological characteristics were determined. In addition, the sensitivity of the pathogen to four microbial fungicides, four botanical fungicides, and five chemical fungicides was determined with the mycelium growth rate method for the purpose of screening out optimal fungicides. The pathogen was identified as Alternaria alternate, as evidenced by the similar colony morphology and microscopic characteristics and 99.55%-100% similarity in sequences of rDNA-ITS, LSU, 18S, and TEF of the two. The optimum growth conditions for A. alternata were 28 ℃, pH 8, and continuous darkness. Bacillus subtilis had strong inhibitory effect on the pathogen, and the inhibition rate was more than 90% when the concentration was 1 mg·L~(-1). In addition, difenoconazole and quinoline copper can also control the pathogen, with median effective concentration(EC_(50)) of 2.92 and 9.02 mg·L~(-1), respectively. This study lays a theoretical basis for the field control of black spot in A. carmichaelii.

Cloning of transcription factor PcFBA-1 in Pogostemon cabin and its interaction with FPPS promoter / 中国中药杂志

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.

UPLC fingerprint and determination of five components of substance benchmark of classical prescription Shentong Zhuyu Decoction / 中国中药杂志

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.

Effects of acupuncture plus medication on hippocampus SIRT1 and FOXO3a expression, MDA content, and SOD activity of rats with Alzheimer disease / 针灸推拿医学（英文版）

Objective: To observe the effect of the acupuncture plus medication on the expression of silent information regulator of transcription 1 (SIRT1) and transcription factor forkhead box protein O3a (FOXO3a) in the hippocampus, the malondialdehyde (MDA) content, and the superoxide dismutase (SOD) activity of rats with Alzheimer disease (AD), and to explore the possible mechanism of combining acupuncture and medication in improving AD-related neurological symptoms. Methods: Sixty male Sprague-Dawley rats were divided into a normal group, a model group, an electroacupuncture (EA) group, a drug group, and an acupuncture-medication combined group by the random number table method, with 12 rats in each group. The model was established by micro-injection of streptozotocin into the bilateral lateral ventricles. After successful modeling, rats in the EA group received EA at Zusanli (ST36) and Dazhui (GV14), those in the drug group received intragastric administration of resveratrol at a dose of 44 mg/(kg·bw), and those in the acupuncture- medication combined group received the combined intervention of EA and resveratrol. Rats in each group received intervention once a day for 4 consecutive weeks. Morris water maze was used to detect the rat behavioral changes. Nissl staining method was used to observe the cell morphology and changes in the number of rat hippocampal neurons. Western blotting and immunohistochemical staining methods were used to observe the expression changes of SIRT1 and FOXO3a. The thiobarbituric acid method was used to detect the MDA content. SOD activity was determined by the hydroxylamine method. Results: Compared with the normal group, the escape latency was significantly prolonged (P<0.05); the percentage of stay in the target quadrant was reduced (P<0.05), the hippocampal neuronal cells were shrunken, nucleoli were unclear, and cell number was reduced (P<0.05); the SIRT1 expression and SIRT1 positive cell number were decreased, while the FOXO3a expression and FOXO3a positive cell number were increased significantly (P<0.05); the MDA content was increased significantly, and the SOD activity was decreased significantly (P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05); the percentage of stay in the target quadrant was increased (P<0.05); the shape and number of hippocampal neurons tended to be normal (P<0.05); the SIRT1 protein expression and the SIRT1 positive cell numbers were increased, the FOXO3a protein expression and the FOXO3a positive cell number were decreased (P<0.05); the MDA content was significantly decreased, and the SOD activity was significantly increased (P<0.05) in the EA group, the drug group, and the acupuncture-medication combined group. The changes in the acupuncture-medication combined group were more obvious (P<0.05). Conclusion: Both EA and resveratrol improve the learning and memory ability of AD rats by regulating the expression of SIRT1 and FOXO3a and improving the levels of MDA and SOD in the hippocampus and protect the hippocampal neurons, while the combined use of EA and medication is more effective than EA or resveratrol alone, suggesting that this combined treatment is more effective in AD treatment.