ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO
COVID-19 ; Cerebrovascular Disorders/epidemiology* ; Comorbidity ; Humans ; SARS-CoV-2 ; Tomography, X-Ray Computed

Objective To investigate the effects of high glucose and lysophosphatidylcholine (LPC) on the immune function of in vitro cultured macrophages during Nocardia farcinica infection. Meth-ods RAW264.7 macrophages were cultured in vitro under different conditions as follows: routine culture (control group),50 mmol/L glucose (high glucose group),10 mg/L LPC(LPC groupⅠ),25 mg/L LPC (LPC groupⅡ) and 50 mmol/L glucose+25 mg/L LPC(high glucose and LPC group). The activity of mac-rophages in each group was tested after 6,12,24 and 36 h of culture. After 24 h of culture, macrophages were collected from every group and co-cultured with Nocardia farcinica. Dynamic phagocytosis rates were detected at 1,2,3,4,5 and 6 h after co-culture. Toxic effects of Nocardia farcinica on macrophages and concentrations of IL-10 and TNF-α were measured at 1,3 and 6 h after co-culture. Results Macrophages in all four experimental groups showed decreased activity as compared with those in the control group (P<0.01). Phagocytosis of Nocardia farcinica by macrophages was also reduced by high glucose and LPC. Phagocytosis rates of high glucose group and LPC groupⅡ at 1 and 2 h,LPC groupⅠat 1,2 and 3 h,and high glucose and LPC group at 1,2,3 and 4 h after co-culture were significantly lower than that of the con-trol group (P<0.05 or P<0.01). Compared with the control group, significantly reduced toxic effects on macrophages caused by Nocardia farcinica was observed in the experimental groups (P<0.05 or P<0.01). Compared with the control group,LPC groupsⅠand Ⅱ and high glucose and LPC group had decreased se-cretion of IL-10 at 3 h,and high glucose group and LPC groupⅠhad decreased secretion of TNF-α at 1 h(P<0.05). Conclusion Culture macrophages under the conditions of high glucose and LPC would reduce their activity and impair their ability to phagocytose Nocardia farcinica. Moreover, high glucose and LPC might have impacts on the toxic effects of Nocardia farcinica on macrophages and the secretion of IL-10 and TNF-α.

AIM:To explore the therapeutic effect of Buyang-Huanwu decoction (BYHWD) on experimental au-toimmune encephalomyelitis ( EAE) and its immunoregulatory effect on monocyte-macrophages .METHODS: Chronic EAE was induced by myelin oligodendrocyte glycoprotein peptide fragment 35-55 ( MOG35-55 ) in the female C57BL/6 mice, which were randomly divided into saline group and BYHWD group .On day 3 after immunization , the mice in BYHWD group were orally administrated with BYHWD , while normal saline was given to the control mice .The clinical score and body mass were recorded every other day .At day 17 after immunization , the mice were sacrificed and spinal cords were obtained for HE staining and myelin staining .The M1 and M2 macrophage phenotypes of splenic cells were detected by flow cytometry and immunofluorescence staining .The protein expression of iNOS , TNF-α, arginase and IL-10 in the spinal cord macro-phages was determined by Western blotting .RESULTS:BYHWD delayed the onset of EAE , reduced the clinical scores of EAE, inhibited the inflammatory cell infiltration and demyelination in the spinal cord , and promoted the conversion of M 1 macrophages into M2 phenotype in the spinal cord and spleen .CONCLUSION:BYHWD intervention attenuates the be-havioral and pathological changes in the EAE mice , and its mechanism may be related to the macrophage conversion .

OBJECTIVE:To study the pharmacokinetics and brain targeting of Toutongning nasal spray in rats in vivo. METH-ODS:84 SD rats were divided into nasal administration group and vein administration group,42 in each group,with dose of 1.2 mL/kg. 5 mL sample blood was taken in abdominal aorta after 5,10,15,30,60,90,120 min of administration,and brain tissue was taken (6 rats in each time point). HPLC-MS was adopted to determine the concentration of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma and brain tissue of rats in each group,and DAS 2.0 software was used to calculate the pharma-cokinetic parameters and brain targeting indexes. RESULTS:The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in nasal administration group were(0.2024±0.0158),(0.3738±0.0857)μg/mL;tmax were(10.0000±0.0000) min;and AUC0-∞ were (16.5429 ± 2.1103),(27.4527 ± 5.5721)μg·h/mL,respectively. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were (0.1802 ± 0.0384),(0.3204 ± 0.0277)μg/g;tmax were (10.0000 ± 0.0000)min;and AUC0-∞ were(17.1053±2.4329),(24.5416±3.7534)μg·h/g,respectively. The cmax of prim-o-glucosylcimi-fugin and 5-O-methylvisammioside in plasma of rats in vein administration group were (0.3002 ± 0.0161),(0.5267 ± 0.0441)μg/mL;tmax were(10.0000±0.0000)min;and AUC0-∞ were(28.0105±4.1128),(60.2941±11.2902)μg·h/mL,respective-ly. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were(0.1498±0.0315),(0.1998± 0.0401)μg/g;tmax were(15.0000±0.0000)min;and AUC0-∞were(22.6434±2.8831),(36.7218±14.8856)μg·h/g,respec-tively. The brain targeting indexes of prim-o-glucosylcimifugin and 5-O-methylvisammioside were 2.3870 and 2.1761,respective-ly. CONCLUSIONS:After nasal administration of Toutongning nasal spray,parts of drugs can directly transport to the brian by na-sal absorption. It is scientific and reasonable to make nasal spray.

Background and objective Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prog-nosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases.Methods Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases.Results There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.Conclusion Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic fac-tor for lung cancer patients with pancreatic metastases.

Objective To investigate the current situation of the pressure load of nurses in the dementia ward of a geriatric hospital, and to provide the intervention for nurses in alleviating the work and life stress of nurses in dementia wards, and in improving the work enthusiasm and the quality of nursing. Methods A total of 35 nurses in dementia ward and 36 nurses in non-dementia ward were surveyed by the questionnaire which the revised Chinese version of the stress load scale. Results The event load dimension score (27.60±6.57) and the individual vulnerability score (26.74±9.70) in the two dimensions of nurses' stress load of dementia ward were higher than those of non-dementia ward nurses, and the differences between the two groups were statistically significant (P<0.05). The top 3 of the stress load items for the dementia ward nurses were all in the event load dimension including "I felt too much pressure and responsibility", "I felt bound by various responsibilities" and "I felt too much to do, but had not enough time". Conclusions Nursing managers should pay attention to the pressure load of nurses in dementia ward, take active measures to intervene, promote the health of nurses and improve their work efficiency and nursing quality.