ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Objective:To summarize the thinking and compatibility law of TCM in the treatment of stable angina pectoris (SAP) based on syndrome differentiation using data mining technology.Methods:The clinical studies of TCM treatment for SAP in databases of CNKI, Wanfang Data, VIP and SinoMed China Biomedical Literature Service System were retrieved from the establishment of the databases to February 28, 2022. The frequency statistic, clustering analysis and association rule analysis of TCM data were conducted using Clementine 12.0, Excel 2016, SPSS Statistics 22.0 software, and core prescriptions were summarized.Results:Totally 289 prescriptions were included, involving 185 kinds of Chinese materia medica, including 38 TCM syndrome types. Based on the overall study of SAP "disease", the clinical treatment of SAP was mainly based on the drugs for activating blood circulation and removing blood stasis, tonifying deficiency and strengthening healthy qi, and regulating qi and resolving phlegm. The single Chinese materia medica with high frequency of use were Chuanxiaong Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Angelicae Sinensis Radix, etc. The commonly used drug pairs included Chuanxiaong Rhizoma-Angelicae Sinensis Radix, Chuanxiaong Rhizoma-Carthami Flos, Chuanxiaong Rhizoma-Aurantii Fructus Immaturus, etc. The drug complex network diagram and clustering analysis showed that the prescription of Buyang Huanwu Decoction was the basic prescription for the treatment of SAP; based on the specific research of SAP "syndrome", the most common TCM syndromes of SAP were qi deficiency and blood stasis, phlegm and blood stasis, and qi stagnation and blood stasis. The drug properties of the three drugs were mainly warm and mild; the tastes were mainly sweet, pungent and bitter, and most of them belong to the liver, spleen, lung and heart meridian; in terms of specific medication, the basic prescription of qi deficiency and blood stasis syndrome was Buyang Huanwu Decoction, which was composed of high-frequency drugs such as Angelicae Sinensis Radix, Chuanxiaong Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, etc; The phlegm and blood stasis syndrome was often based on the Gualou Xiebai Banxia Decoction and Taohong Siwu Decoction, which were composed of high frequency drugs such as Pinelliae Rhizoma, Chuanxiaong Rhizoma, Allii Macrostemonis Bulbus, etc; the basic prescription of qi stagnation and blood stasis syndrome was Xuefu Zhuyu Decoction, which was composed of high frequency drugs such as Chuanxiaong Rhizoma, Angelicae Sinensis Radix, Aurantii Fructus. Drug clustering analysis showed that both qi deficiency and blood stasis syndrome and qi stagnation and blood stasis syndrome were divided into 3 categories, and phlegm and blood stasis syndrome were divided into 4 categories.Conclusions:Deficiency, blood stasis, phlegm and stagnation are important pathological factors of SAP, in which qi deficiency is the basis of SAP, blood stasis runs through the disease, or both phlegm and qi stagnation. Focusing on the pathogenesis of deficiency in root and excess in superficiality, drugs with the efficacy of tonifying the deficiency and promoting blood circulation and removing blood stasis are used in clinical treatment, according to different syndrome differentiation of prescription selection.

Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

Objective:To explore the feasibility of rapid identification of methicillin-resistant Staphylococcus aureus using different algorithms of the matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer. Methods:Totally 314 clinical isolates of Staphylococcus aureus were selected from the bacterial bank at Beijing Tongren Hospital from January 2017 to June 2019. The samples were identified by MALDI-TOF MS, and screened by cefoxitin disk method (inhibition ring diameter ￡21 mm) and PCR mecA gene. The strains were divided into a methicillin-resistant Staphylococcus aureus (MRSA) group (130 strains) and a methicillin-susceptible Staphylococcus aureus (MSSA) group (184 strains). Then, after collecting the spectrograms of these samples using formic acid extraction, the MRSA group and MSSA group were divided into three subgroups each, namely MRSA-1 (43 strains), MRSA-2 (42 strains), MRSA-3 (45 strains) and MSSA-1 (60 strains), MSSA-2 (61 strains) and MSSA-3 (63 strains). The groups were studied using genetic algorithm (GA), fast classification algorithm (QC) and supervised neural network algorithm (SNN) in the ClinProTools software on the Bruker MALDI-TOF mass spectrometer, and the convolutional neural network algorithm (CNN) in the Ex-SmartSpec software on the Zhongyuan Hui-Ji mass spectrometer. These studies were repeated for 3 rounds. The first round with MRSA-1 and MRSA-2, MSSA-1 and MSSA-2 being model groups, MRSA-3 and MSSA-3 being validation groups. The validation groups were rotated for each round. The areas under the receiver operating characteristic (ROC) curve expansions of the four algorithms were used to confirm each program′s performance. Then, 38 MRSA strains and 40 MSSA clinical strains were selected from the bacterial bank of the Laboratory of Beijing Tongren Hospital from July 2019 to December 2019, and were put through the formic acid extraction method to collect their spectra. These samples were tested independently with their convolutional neural network models. Results:After three rounds of modeling and verification, the areas under the ROC curves of the three Bruker ClinProTools programs were as follows: for genetic algorithm, the areas were 0.89, 0.74, and 0.64 respectively; for fast classification algorithm, the areas were 0.77, 0.95, and 0.94 respectively; and for supervised neural network algorithm, the areas were 0.90, 0.98, and 0.98 respectively. The areas under the ROC curves of the convolutional neural network algorithm with Zhongyuan Huiji mass spectrometer′s Ex-SmartSpec software were 0.95, 0.99, and 0.99 respectively. The independent test results of convolutional neural network algorithm showed that these results have an accuracy, specificity, sensitivity and AUC of 88.82% (810/912), 81.15% (779/960), 84.88% (1 589/1 872) and 0.92 respectively.Conclusions:The supervised neural network algorithm of Bruker′s ClinProTools and the convolutional neural network algorithm of Zhongyuan Hui-Ji mass spectrometer′s EX-Smartspec is clinically acceptable for rapid identification of MRSA performance indicators. Using convolutional neural network algorithm and MALDI-TOF mass spectrometry, MRSA strains can be identified quickly, providing timely advice for clinical medications.

In order to investigate the molecular mechanism of silk/threonine protein kinase (STK)-mediated blue light response in the algal Chlamydomonas reinhardtii, phenotype identification and transcriptome analysis were conducted for C. reinhardtii STK mutant strain crstk11 (with an AphvIII box reverse insertion in stk11 gene coding region) under blue light stress. Phenotypic examination showed that under normal light (white light), there was a slight difference in growth and pigment contents between the wild-type strain CC5325 and the mutant strain crstk11. Blue light inhibited the growth and chlorophyll synthesis in crstk11 cells, but significantly promoted the accumulation of carotenoids in crstk11. Transcriptome analysis showed that 860 differential expression genes (DEG) (559 up-regulated and 301 down-regulated) were detected in mutant (STK4) vs. wild type (WT4) upon treatment under high intensity blue light for 4 days. After being treated under high intensity blue light for 8 days, a total of 1 088 DEGs (468 upregulated and 620 downregulated) were obtained in STK8 vs. WT8. KEGG enrichment analysis revealed that compared to CC5325, the crstk11 blue light responsive genes were mainly involved in catalytic activity of intracellular photosynthesis, carbon metabolism, and pigment synthesis. Among them, upregulated genes included psaA, psaB, and psaC, psbA, psbB, psbC, psbD, psbH, and L, petA, petB, and petD, as well as genes encoding ATP synthase α, β and c subunits. Downregulated genes included petF and petJ. The present study uncovered that the protein kinase CrSTK11 of C. reinhardtii may participate in the blue light response of algal cells by mediating photosynthesis as well as pigment and carbon metabolism, providing new knowledge for in-depth analysis of the mechanism of light stress resistance in the algae.
Chlamydomonas reinhardtii/genetics* ; Photosynthesis/genetics* ; Plants/metabolism* ; Protein Kinases ; Threonine/metabolism* ; Carbon/metabolism* ; Serine/metabolism*

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Objective:To observe the morphological and hemodynamics changes of aortic segments in mice with angiotensinogen Ⅱ(Ang II) combined with β-aminopropionitrile(BAPN) induced-aortic dissection by color Doppler ultrasound(CDUS).Methods:Twenty male mice of 6-8 weeks old C57BL/6 were randomly divided into two groups: the model group( n=10) was induced by intraperitoneal injection of Ang Ⅱ combined with BAPN to establish mice model with aortic dissection; the control group( n=10) was intraperitoneally injected with normal saline.The body weight, systolic and diastolic blood pressure of the mice were routinely recorded. On the 42th day, CDUS was used to measure the indexes of ascending aorta(AoA), descending thoracic aorta(DAo) and suprarenal aorta(SAo) in both groups, including the inner diameter of the cross section, peak systolic velocity(PSV), the end diastolic velocity(EDV), the resistance index(RI), the pulsatility index(PI), time average mean velocity(TAMV), the heart rate(HR) and the maximal shear rate(SR). Then, the aortas were harvested from the root to the bifurcation of the renal artery. The pathological changes of the aortic wall were observed using hematoxylin-eosin(HE) staining. Results:①There were statistically significant differences in body weight, systolic blood pressure, diastolic blood pressure and heart rate between the model group and the control group(all P<0.05). Compared with the control group(0/10), the incidence of the AoA dissection(8/10) in the model group was obviously higher, the difference was statistically significant( P<0.05); while the incidence of the DAo dissection(4/10) and the SAo dissection(3/10) in the model group was slightly higher, the differences were not statistically significant (all P>0.05). ②Compared with the ascending aorta of the control group, the inner diameter, PSV, EDV, TAMV, PI and SR in the model group were significantly higher(all P<0.05), while RI showed no significant difference between the two groups ( P>0.05). For the descending thoracic aorta, PSV, EDV, TAMV, PI and SR in model group were higher than those of the control group(all P<0.05), however the inner diameter and RI were not significantly different between the two groups (all P>0.05). And for the superior renal aorta, PSV, TAMV, RI, PI and SR in the model group were obviously higher than the control group(all P<0.05), whereas the inner diameter and EDV were not significantly different between the two groups (all P>0.05). ③The HE of the tissue section in the model group showed, the aortas were obviously dilated, irregular, with inhomogeneously thickening wall; the endothelial cell nuclei were slightly stained, and some intima and middle layer ruptured and protruded outward to form dissecting aneurysms. The adventitias were markedly infiltrated with inflammatory cells. Conclusions:Ultrasonography could primarily evaluate the hemodynamic changes of aorta in hypertension with aortic dissection, and the PSV, TAMV, PI and SR of aorta may be important indicators for early predicting the occurrence of aortic dissection in hypertension.

Objective:To investigate the role of stress-inducible protein Sestrin2 (Sesn2) in the improvement of insulin resistance in rat L6 skeletal muscle cells treated with liraglutide.Methods:The establishment of insulin resistance model of rat L6 skeletal muscle cells was induced by palmitate. The experimental cells were divided into control group(Con group), palmitate 0.6 mmol/L treatment group(PA group), palmitate 0.6 mmol/L+ liraglutide 10 nmol/L treatment group(PA+ Lir10 group), palmitate 0.6 mmol/L+ liraglutide 100 nmol/L treatment group(PA+ Lir100 group), and palmitate 0.6 mmol/L+ liraglutide 1 000 nmol/L treatment group(PA+ Lir1000 group). The cell counting kit 8(CCK8) method was used to detect the cell activity in each group. Western blotting was used to detect the expression levels of glucose transporter 4(GLUT4), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), and Sesn2 protein in L6 cells. L6 cells were transfected with siRNA to inhibit the expression of Sesn2. The cells were treated with palmitate and liraglutide. Western blotting was used to detect the expression levels of Sesn2, Akt, p-Akt, and GLUT4 protein in L6 cells.Results:Compared with Con group, the cell survival rate, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression in PA group decreased significantly( P<0.05). After liraglutide intervention, the cell activity, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression of PA+ Lir100 and PA+ Lir1000 groups was increased( P<0.05). After inhibiting the expression of Sesn2, p-Akt/Akt ratio and GLUT4 protein in transfected si-Sesn2 and treated with 0.6 mmol/L palmitate group(PA+ si-Sesn2 group) and transfected si-Sesn2 and treated with 0.6 mmol/L palmitate+ liraglutide 100 nmol/L group (Lir100+ PA+ si-Sesn2 group) were significantly lower than those in transfection negative group (si-Con group; P<0.05). Even after liraglutide intervention, compared with PA+ si-Sesn2 group, p-Akt/Akt ratio and GLUT4 protein expression level were not significantly increased in Lir100+ PA+ si-Sesn2 group ( P>0.05). Conclusions:Palmitate could induce the decrease of p-Akt/Akt ratio and GLUT4 protein expression in L6 cells. Liraglutide upregulates the expression of Sesn2, which leads to the increase of p-Akt/Akt ratio and GLUT4 protein expression and contributes to the improvement of insulin resistance.