Glaucoma is a group of neurodegenerative disease characterized by progressive retinal ganglion cells (RGCs) death and visual field defect.Although its pathological mechanism is unclear,elevated intraocular pressure is considered to be the main contributing factor.As the main components of the aqueous humor drainage system,the structural abnormalities,dysfunction of trabecular meshwork and Schlemm canals may cause aqueous humor outflow obstruction and result in elevated intraocular pressure.Increasing evidences suggest that oxidative stress is the key factor leading to the apoptosis,dysfunction of the human trabecular meshwork cell,and other progression of degenerative changes.Oxidative damage is an imbalance between the oxidative stress and anti-oxidative system,which leads to lipid peroxidation,protein denaturation and DNA damage.Previous studies showed that the level of oxidative biomarker was elevated in the aqueous humor of glaucoma patients.In addition,oxidative stress is thought contributing to the pathogenesis of DNA damage,mitochondrial dysfunction and inflammation in human trabecular meshwork cells.This review considered the contribution of oxidative stress on human trabecular mesh work dysfunction and its possible mechanisms.

Objective To investigate the predictive and guiding significance of peripheral blood biomarkers on the therapeutic effects of PD-1/PD-L1 inhibitor treatment on lung cancer patients. Methods We collected the data of 200 lung cancer patients treated with PD-1/PD-L1 inhibitors treatment, including clinical indicators, peripheral blood indicators, efficacy indicators and survival indicators. Results The DCR of patients with non-hepatic metastasis, immune combined chemotherapy, NLR≤2.81 and LDH≤202.5 u/L was higher (P < 0.05). The AUC value of NLR combined with LDH predicting DCR was 0.698 (P < 0.05). Univariate analysis showed that non-hepatic metastasis, first-line immunotherapy, immunotherapy combined with chemotherapy and LDH≤202.5 u/L were related to PFS (P < 0.05). Multivariate analysis showed that the patients with non-hepatic metastasis and LDH≤202.5 u/L had longer PFS (P < 0.05). The significant decrease of NLR and LDH after two cycles of immunotherapy indicated the effectiveness of immunotherapy (P < 0.05). Conclusion NLR≤2.81, LDH≤202.5 u/L, non-hepatic metastasis and immunotherapy combined chemotherapy are positively correlated with immunotherapy efficacy. Non-hepatic metastasis and LDH≤202.5 u/L are independent prognostic factors of the patients treated with immunotherapy. The changes of peripheral blood NLR and LDH are related to the efficacy of PD-1/PD-L1 inhibitors treatment.

Objective:To investigate the prognostic value of texture analysis of MRI diffusion weighted imaging (DWI) for neonatal hypoglycemic encephalopathy (HE).Methods:The clinical data and MRI data of 119 patients with neonatal HE admitted to Children′s Hospital of Nanjing Medical University from July 2013 to September 2020 were retrospectively analyzed. The children were followed up to 7—8 months and scored by Bayley scales of infant and toddler development. According to the overall development index, the children were divided into three groups: normal group (≥85, group A, n=42), mild developmental retardation group (70－84, group B, n=46) and developmental retardation group (≤69, group C, n= 31). The whole brain region (except sulcus and cisterna) was delineated as region of interest (ROI) by LIFEx 3.4 software in MRI apparent diffusion coefficient images. A total of 37 parameters were calculated automatically by the software, The clinical data, including gender, gestational age, age at MRI scan, birth weight, mode of delivery, history of asphyxia at birth, maternal preeclampsia or diabetes, minimum blood glucose, duration of hypoglycemia, neonatal behavioral neurological assessment (NBNA), presence or absence of polycythemia); the texture parameters, including histogram, volume, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), neighborhood gray tone difference matrix (NGTDM), gray level size zone matrix (GLSZM), in the three groups were analyzed; and the diagnostic efficacy of clinical parameters and texture parameters was analyzed. Multivariate Logistic regression was used to analyze statistically significant clinical parameters and texture parameters, and receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficacy of these parameter for neonatal HE. Results:There were no significant differences in gender, gestational age, age at MRI scan, delivery mode and blood glucose minimum among the three groups ( P>0.05). There were significant differences in birth weight [(3 150±130)g, (3 020±220)g, (2 880±140)g, F=-0.31, P=0.015], history of suffocation (10 cases, 18 cases, 20 cases, P=0.001), history of maternal diabetes or preeclampsia (14 cases, 29 cases, 21 cases, P=0.002), blood glucose duration [(5.0±0.2)d, (8.0±0.4)d, (14.0±1.7)d, F=-3.09, P=0.030] and NBNA scores (32.0±3.2, 28.0±2.6, 22.0±1.9, F=-4.21, P=0.010) among three groups. There were significant differences in kurtosis and entropy of histogram (2.57±1.12, 3.66±0.98, 4.23±0.37, F=3.54, P=0.010;5.89±1.09, 7.67±2.12, 8.92±1.62, F=-4.42, P=0.020); energy, contrast and dissimilarity of GLCM (0.48±0.01, 0.36±0.02, 0.23±0.01, F=-3.12, P=0.001;2 419±21, 3 354±31, 4 313±26, F=-4.16, P=0.020;126±14, 153±23, 344±43, F=-3.50, P<0.001); long run emphasis of GLRLM (0.78±0.15, 1.12±0.12, 1.76±0.31, F=-4.13, P=0.006), run length non-uniformity and run percentage (71.7±13.9, 96.6±10.7, 104.1±13.5, F=-0.98, P=0.001;0.91±0.05, 0.84±0.21, 0.72±0.17, F=2.97, P=0.010); coarseness and busyness of NGTDM [0.09±0.01, 0.13±0.03, 0.26±0.07, F=-1.95, P=0.003;0.16(0.04, 4.14), 0.32(0.05, 9.84), 0.45(0.15, 10.14), H=-3.24, P=0.030], short-zone emphasis and short-zone high gray length emphasis of GLSZM (4.74±0.45, 3.44±1.03, 1.88±0.67, F=-3.14, P=0.040; 278 963±239, 164 607±544, 111 653±618, F=-3.84, P=0.001) among three groups. Multivariate Logistic regression showed that duration of hypoglycemia, NBNA score, energy, kurtosis, run percentage and short zone effect were independent risk factors for poor prognosis of neonatal HE ( OR=7.43, 4.09, 1.10, 2.11, 1.36, 1.68, P=0.002, 0.027, 0.001, 0.006, 0.007, 0.010, respectively). ROC curve showed that for combined hypoglycemic duration, NBNA and texture parameters, the area under the curve (AUC) was the highest (AUC=0.94, P<0.001). Conclusion:Texture analysis of the MRI diffusion weighted imaging can predict the prognosis of neonatal hypoglycemic encephalopathy at an early stage, which has better prediction efficiency when combined with clinical features.

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg^-1）， paeoniflorin （50 mg·kg^-1） + inhibitor （20 mg·kg^-1） group， and high dose （50 mg·kg^-1）， medium dose （25 mg·kg^-1）， and low dose （12.5 mg·kg^-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.