Risk factors for prolonged postoperative ileus after radical colorectal cancer resection / 中华普通外科杂志

Objective:To investigate the prognostic factors for the risk of prolonged postoperative ileus (PPOI) after colorectal cancer resection.Methods:The clinical data of 896 patients undergoing radical colorectal cancer resection at Affiliated Hospital of Qingdao University between Jan 2016 and Dec 2022 were retrospectively analyzed. Patients were divided into PPOI group (59 cases) and non-PPOI group (837 cases) according to whether PPOI happened after surgery. Potential prognostic factors for the risk of developing PPOI were analyzed by univariate and multivariate Logistic regression. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:Fifty-nine patients (6.5%) developed PPOI after radical colorectal cancer resection. Univariate and multifactorial logistic regression analyses showed that diabetes mellitus ( OR=2.360, P=0.018), preoperative albumin level <35 g/L ( OR=2.196, P=0.036), postoperative epidural analgesia ( OR=2.399, P=0.007), open surgery ( OR=3.413, P=0.001), and ICU hospitalization ≥ 48 h ( OR=6.134, P<0.001) were independent prognostic factors for PPOI. Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.698-0.838), with an accuracy, sensitivity and specificity of 73.9%, 74.0%, 72.9%, respectively. Conclusion:Diabetes mellitus, preoperative albumin level, postoperative epidural analgesia, open surgery, and ICU hospitalization ≥ 48 h were risk factors for PPOI after radical colorectal cancer resection.

Treatment of Paroxysmal Sympathetic Hyperactivity by the Method of “Returning Fire to Its Origin” / 中医杂志

This paper summarized the clinical experience of using the method of “returning fire to its origin” for treatment of paroxysmal sympathetic hyperactivity （PSH）. According to the causes and clinical characteristics of PSH， the author believes that the deficiency of kidney qi， and the loss of yin and yang are the basis of the pathogenesis of PSH. Fright causes qi to be chaotic as the triggering mechanism of PSH. The key mechanism of PSH is that the deficiency yang with upper manifestation， and the fire does not return to its origin. The treatment should be nourishing yin and astringing yang， by taking modified Yinhuo Decoction （引火汤） internally， and receiving warm moxibustion as the first choice externally with selected acupoints Guanyuan （CV 4）， Mingmen （GV 4）， and bilateral Yongquan （KI 1）； For prevention， attention should be paid to take care of stomach qi， support healthy qi， and cultivate original qi.

Research progress of microRNA in oxidative stress and lipid metabolism of non-exudative age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

Effect of Baicalin on Pyroptosis of Diffuse Large B-Cell Lymphoma Cell Lines DB and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism.@*METHODS@#DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC50) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture.@*RESULTS@#Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC50 was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production.@*CONCLUSION@#Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.

Regulation of Baicalin on Growth of Extranodal NK/T Cell Lymphoma Cells through FOXO3/CCL22 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism.@*METHODS@#Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation.@*RESULTS@#In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001).@*CONCLUSION@#Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.

Risk factors of cerebral infarction in patients with primary antiphospholipid syndrome / 中华风湿病学杂志

Objective:To analyze the clinical manifestations, risk factors and risk of recurrence in patients with primary antiphospholipid syndrome (PAPS) complicated with cerebral infarction.Methods:Inpatients diagnosed with PAPS was recruited between 2010 and 2020. Clinical characteristics,laboratory results and adjusted global antiphospholipid syndrome score (aGAPSS) were compared between patients with cerebral infarction and without cerebral infarction by χ2 test, t test or Mann-Whitney U test. Univariate and multivariate Logistic analysis were performed to identify the risk factors associated with cerebral infarction. Results:In 145 PAPS patients [median age 44.0 (34.0, 51.5) years, 66.2% female], 46 (31.7%) patients had cerebral infarction. Patients with cerebral infarction had higher rates of transient ischemic attack (TIA) (50.0% and 20.2%, χ2=13.37, P<0.001), cardiac valvular anomalies (32.6% and 11.1%, χ2=9.86, P=0.002), lupus anticoagulant (LA) (87.0% and 42.4%, χ2=25.35, P<0.001) and triple antiphospholipid antibodies (aPL) positivity (50.0% and 11.1%, χ2=26.64, P<0.001). The aGAPSS value was significantly higher in patients with cerebral infarction compared to those without [13(11, 14) and 9(7, 13), U=934.50, P<0.001]. The independent risk factors for PAPS-associated cerebral infarction were TIA [ OR (95% CI)= 3.612 (1.387, 9.403), P=0.009]、triple aPL positivity[ OR(95% CI)=8.904 (3.169, 25.019), P<0.001], higher aGAPSS[ OR(95% CI)=1.421(1.209, 1.670), P<0.001]. Conclusion:Patients with cerebral infarction may have a higher risk of thrombus recurrence. TIA, triple aPL positivity and higher aGAPSS are independent risk factors for PAPS patients with cerebral infarction.

Cohort study on the change trend of astigmatism among preschool children in Baiyun district, Guangzhou from 2018 to 2021 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the characteristics of astigmatism in preschool children before, during and after the COVID-19 epidemic, so as to provide a reference for further prevention and control of children's vision.METHODS: In the consecutive four years from January 2018 to December 2021, a retrospective analysis of vision data was conducted on 2 273 preschool children(4 546 eyes)younger than 4 years old who participated in children's vision screening test in Baiyun district, Guangzhou. They were divided into 1-year old group(ages&#x003C;1-year old, 420 cases), 2-year old group(1-year ≤ ages &#x003C;2-year, 543 cases), 3-year old group(2-year ≤ages &#x003C;3-year, 614 cases), and 4-year old group(3-year ≤ ages&#x003C;4-year, 696 cases)according to ages. The analysis included astigmatic degrees of children's eyes as well as their conditions of astigmatism.RESULTS: In 2018, the astigmatic degrees of the both eyes of 1-year-old group were higher than those of other groups(P&#x003C;0.05). The binocular astigmatic degrees of the preschool children in four groups were obviously higher in 2020 than 2019(P&#x003C;0.05), while they were significantly decreased in 2021 when compared with 2020(P&#x003C;0.05). From 2019 to 2020, the increase of astigmatic degrees of the right eye is more considerable than the left eye of preschool children in those four groups(P&#x003C;0.001). Furthermore, the morbidity of astigmatism basically echoes with the changing tendency of astigmatic degrees from 2018 to 2021.CONCLUSIONS: Preschool children in Baiyun district, Guangzhou, have the highest degree of astigmatism and the fastest progression rate within 1 year old. Before COVID-19 epidemic, the changes in astigmatism and prevalence were relatively stable; during COVID-19 epidemic, the astigmatism and prevalence increased significantly and the astigmatic degrees of right eye increased more than that of the left eye; after the normalization of epidemic prevention and control, the astigmatism and prevalence decreased significantly.

Molecular Mechanism of Wendantang Against Schizophrenia in Rats： An Exploration Based on miRNA-219， NR2B， DISC1 and CaMKⅡγ / 中国实验方剂学杂志

ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.

Molecular Mechanism of Jingfang Mixture Against H1N1 Influenza Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the potential targets and mechanism of Jingfang mixture in the treatment of H1N1 influenza and provide references for clinical application of Jingfang mixture. MethodThe active components and targets of Jingfang mixture against H1N1 influenza were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），SwissTargetPrediction， and TargetNet. The targets of H1N1 influenza were obtained from GeneCards，Online Mendelian Inheritance in Man （OMIM）， and DisGeNET and standardized by UniProt KB. The intersection targets were obtained by Venny 2.1.0. The "drug-component-target" network was constructed with Cytoscape 3.2.1 and analyzed for the topological attributes. The intersection targets were uploaded to STRING 11.5 to obtain the protein-protein interaction （PPI） network. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis were carried out by Metascape. Finally，the top active components ranked by degree were docked to the core targets by Autodock vina and visually analyzed by PyMOL. Balb/c female rats were used for experimental verification. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in lung tissues. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of tumor necrosis factor-α（TNF-α），interleukin-10（IL-10）， and interleukin-17（IL-17）. Real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels in lung tissues. ResultThere were 144 active components in Jingfang mixture. A total of 421 target genes of Jingfang mixture and 2 956 targets of H1N1 influenza were identified，including 199 common targets. Topological analysis showed that the core components of Jingfang mixture against H1N1 influenza included quercetin，luteolin， and kaempferol，and the core targets included prostaglandin-endoperoxide synthase 2（PTGS2），estrogen receptor alpha（ESR1），inducible nitric oxide synthase 2（iNOS2），peroxisome proliferator-activated receptorγ（PPARγ），and cyclooxygenase-1（PTGS1）. GO enrichment yielded 697 items in biological process （BP） （P<0.01）， 59 items in molecular function （MF）（P<0.01）， and 21 items in cellular component （CC） （P<0.01）. A total of 132 signaling pathways （P<0.01） were obtained by KEGG enrichment analysis， including phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway，most of which were related to the regulation of immune inflammation. Molecular docking showed that the binding energy of the active components of Jingfang mixture to the core targets was less than -5.0 kcal·mol-1，indicating good binding activity. HE staining showed that the lung tissues were significantly improved after drug intervention，and Real-time PCR and Western blot showed that Jingfang mixture could reduce the mRNA and protein expression of PI3K and Akt in lung tissues. ConclusionJingfang mixture can play an anti-viral effect against the influenza A virus through multiple components，multiple targets， and multiple pathways. The active components quercetin，luteolin， and kaempferol may control the inflammation and regulate immunity on the PI3K/Akt，MAPK， and other signaling pathways by acting on targets such as PTGS2，ESR1，iNOS2，PPARγ， and PTGS1.

Effect of PEG-rhG-CSF in Preventing Chemotherapy-induced Neutropenia in Locally Advanced Non-small Cell Lung Cancer Patients at Nutritional Risk / 肿瘤防治研究

Objective To explore the efficacy and safety of polyethylene glycol recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in locally advanced non small cell lung cancer (NSCLC) patients at nutritional risk. Methods A total of 337 locally advanced NSCLC patients at nutritional risk were selected. They were randomly divided into three groups: 112 cases in the non-prophylactic drug group (control group), 112 cases in the prophylactic use of rhG-CSF treatment group (rhG-CSF group), and 113 cases in the prophylactic use of PEG-rhG-CSF treatment group (PEG-rhG-CSF group). The incidence and duration of neutropenia after chemotherapy and the ratio of CD4+/CD8+T cells in peripheral blood were observed. Results The incidences of neutropenia in the control group, rhG-CSF group, and PEG-rhG-CSF group were 67.97%, 41.57%, and 38.98% (P < 0.05), respectively. The incidences of grade Ⅲ-Ⅳ neutropenia in the three groups were 22.39%, 14.25%, and 11.14% (P < 0.05); moreover, the incidence of febrile neutropenia in the three groups was 3.55%, 1.84%, and 1.21% (P < 0.05); in addition, the ratios of CD4+/CD8+T cells in peripheral blood were 1.27±0.44, 1.41±0.52, and 1.49±0.42 (P < 0.05). The duration of grade Ⅲ-Ⅳ neutropenia and the time required for the neutrophil value to reach 2.0×109/L from the lowest value in the PEG-rhG-CSF group were lower than those in the control and rhG-CSF groups (P < 0.05). Conclusion The PEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy in locally advanced NSCLC patients at nutritional risk can reduce the incidence of neutropenia and improve immunologic function. PEG-rhG-CSF preventive treatment is worthy of clinical recommendation.