ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure （POF） based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank， model， and low- and high-dose （2， 8 g·kg^-1， respectively） Zuoguiwan groups， with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg^-1 on the first day and 8 mg·kg^-1 from the second day to the fifteenth day for the modeling of POF. After modeling， the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， anti-Mullerian hormone （AMH）， malondialdehyde （MDA）， catalase （CAT）， superoxide dismutase （SOD）， and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， ferritin heavy chain （FTH1）， and acyl-CoA synthetase long chain family member 4 （ACSL4）. ResultCompared with the blank group， the model group showcased significantly increased atretic follicles， atrophied， fragmented， and vacuolated mitochondria， and reduced， loose， and disordered cristae in mitochondria. Compared with the model group， high-dose Zuoguiwan increased mature follicles， the volume of mitochondria in the ovary， alleviated the vacuolation， and improved the number and arrangement of mitochondrial cristae. Compared with the blank group， the modeling elevated the levels of iron， MDA， FSH， and LH， up-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， decreased the activities of SOD and CAT， lowered the levels of E₂ and AMH， and down-regulated the expression of ACSL4 （P<0.05， P<0.01）. Compared with the model group， drug interventions lowered the levels of iron， MDA， FSH， and LH， down-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， increased the activity of CAT， elevated the levels of E₂ and AMH， and up-regulated the expression of ACSL4 （P<0.05， P<0.01）. ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis， thereby improving the ovarian function of POF rats.

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg^-1·d^-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg^-1·d^-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E₂， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.
Biomarkers ; Carrier Proteins ; Child ; Humans ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Macrolides ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma/drug therapy* ; Proteomics

Under the diagnosis-related groups(DRG) prospective payment system, innovative health technologies with high costs and risks may be limited to some extent. How to balance the increase of health care cost and the development of innovative health technology is a difficult problem to be solved in the current reform. By studying the relatively mature payment systems of innovative health technologies in the world, the authors found that countries generally adopted additional payment or compensation to encourage the development of new technologies. But at the same time, a relatively perfect health technology assessment and payment management mechanism had been established to ensure the standardized operation of payment plan. These international advanced experience and practice could provide references for China′s innovative health technology payment strategy under the DRG payment system. It is suggested to establish a scientific and reasonable assessment mechanism of innovative health technology, create a special access channel for innovative health technology with limited short-term evidence, and gradually form a long-term incentive mechanism of innovative health technology in DRG payment system.

The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations

Objective:To evaluate the application efficacy of enhanced recovery after surgery(ERAS)in laparoscopic colorectal cancer surgery in primary hospitals.Methods:A total of 116 patients who underwent laparoscopic colorectal cancer surgery from January 2017 to December 2018 at our hospital were enrolled in this study.According to the perioperative rehabilitation program, 116 patients were divided into the group A(n=67, receiving enhanced recovery after surgery)and the group B(n=49, receiving traditional recovery after surgery).Results:The incidences of preoperative thirst and hunger were lower in the group A than in the group B(11.9% vs.53.1%, 16.4% vs.51.0%, χ2=23.10 and 15.83, respectively, P<0.001). The levels of CRP and blood glucose in the two groups were significantly higher after operation than before operation, and reached the peak values on the 3rd day after the operation.At different time points after operation, CRP levels and blood glucose levels were higher in the group B than in the group A(all P<0.05). On the 7th day after operation, blood glucose level was recovered to the preoperative level in the group A, while it was not so in the group B. The incidence of complication in the group A was similar to the group B(7.46% vs.12.2%, χ2=0.75, P>0.05). The hospitalization period was shorter and the hospitalization cost was less in the group A than in the group B(8.16±1.33)d vs.(15.39±2.81)d, (46100±1800)yuan vs.(56900±5600)yuan, t=10.98 and 9.96, P=0.000). Conclusions:The application of enhanced recovery after surgery is beneficial for perioperative safety, can reduce surgical stress response, promote postoperative recovery, shorten hospitalization time after surgery and reduce hospitalization costs in laparoscopic colorectal cancer surgery.

Objective: To explore an effective long non-coding RNA (lncRNA) signature in predicting the prognosis of hepatocellular carcinoma through the analysis on RNA sequencing data of hepatocellular carcinoma patients and peritumoral tissues in the Cancer Genome Atlas (TCGA) database. Methods: The clinical characteristics and RNA sequencing data of 377 hepatocellular carcinoma patients were obtained from TCGA database by the end of February 2018. Then, differentially expressed lncRNAs between 50 pairs of tumor and peritumoral tissues were explored using student’s t-test. Next, a lncRNA signature was established through LASSO Cox regression analysis. All the patients were divided into four groups (<P₂₅, P₂₅-, P₅₀-, ≥P₇₅) based on the cut-off quartiles signature. Finally, compared with the control group (<P₂₅), the hazard ratios (HRs) of three groups (P₂₅-, P₅₀-, ≥P₇₅) were calculated by using Cox regression. The survival outcomes of patients in the four groups were compared to evaluate the capacity of the lncRNA signature model. Results: A total of 951 differentially expressed lncRNAs were identified between tumor and peritumoral tissues. A three-lncRNA signature, including LNCSRLR, MKLN1-AS and ZFPM2-AS1, was established to predict the prognosis of hepatocellular carcinoma patients. The outcome suggested that the death risk of the ≥P₇₅ group was 1.57 times larger than that of the <P₂₅ group (95%CI: 1.06-2.31, P<0.05). Conclusion The three-lncRNA signature, which established by LNCSRLR, MKLN1-AS and ZFPM2-AS1, was significantly associated with the prognosis of hepatocellular carcinoma patients based on TCGA database data.

Objective To investigate the clinical efficacy of low-frequency transcranial magnetic stimulation (rTMS) on post-stroke upper limb spasticity and its mechanism. Methods From September, 2015 to December, 2017, 23 patients with post-stroke upper limb paralysis were randomly divided into control group (n=13) and experimental group (n=10). Both groups received routine rehabilitation, and the experimental group received 1 Hz rTMS at primary motor area (M1) for eight weeks. They were assessed with modified Ashworth Scale (MAS), modified Barthel Index (MBI) and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) before and after treatment, while the activation under fMRI in the task state was observed and the laterality index (LI) was calculated. Results The scores of MAS, FMA-UE and MBI improved after treatment in both groups (Z>2.121, t=6.248, P<0.05), and improved more in the experimental group than in the control group (Z>2.084, t=-2.095, P<0.05). The ipsilateral M1, ipsilateral sensory motor cortex and bilateral supplementary motor area were activated more in the control group than in the experimental group during the movement of affected hand. LI in the M1 increased after treatment in both groups (Z>2.366, P<0.05), and was more in the experimental group than in the control group (Z=-2.430, P<0.05). There was a positive correlation between the change of LI in the M1 and the improvement of the MAS and FMA-UE (r>0.612, P<0.05). Conclusion Low-frequency rTMS may improve the motor function and spasticity of upper limb after stroke by promoting reorganization of the cortex and inducing normalization of cortical function.

Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm) or normal saline as control (larger than 2000 nm). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.

Objective To investigate the clinical efficacy of neoadjuvant chemoradiotherapy in the treatment of locally advanced low and middle rectal cancer,and evaluate the effect of related clinical factors upon the long-term survival. Methods Clinical data of 101 patients with locally advanced low and middle rectal cancer admitted to our hospital from January 1,2010 to December 31,2014 were collected. All patients completed the preoperative intensity-modulated radiation therapy DT45-50. 4 Gy,synchronized with oxaliplatin+capecitabine/5-fluorouracil or single drug capecitabine chemotherapy,and total mesorectal excision) was performed 4-13 weeks after the end of the neoadjuvant therapy. The short-term efficacy and long-term prognosis of these patients were evaluated. Kaplan-Meier method was used for survival analysis,and Cox’s regression model for multivariate analysis. Results The total sphincter preservation rate was 53. 5%.The decrease rates of T,N staging and TNM total staging were 73. 26%,67. 32% and 72. 3%,respectively. The pathological complete response ( pCR) rate was 16. 8%.The median follow-up time was 41 months. The 3-year overall survival (OS), desease-free survival (DFS),local recurrence and distant metastases rates were 82. 2%,80. 7%,7. 2% and 12. 1%,respectively. The single factor analysis demonstrated that ypT and ypN stages were the risk factors affecting the 3-year OS,DFS anddistant metastases ( all P＜0. 05).Multivariate analysis revealed that ypT stage was an independent factor affecting the 3-year OS,and ypT and ypN stages were the independent factors of the 3-year DFS ( all P＜ 0. 05 ). ConclusionsNeoadjuvant chemoradiotherapy combined with TME in the treatment of locally advanced middle and low rectal cancer can partially decrease the tumor staging,enhance the sphincter preservation rate and improve long-term clinical prognosis. Both ypT and ypN stages are correlated with the clinical prognosis of patients.