ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang （MHGW） on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α （IRE1α） and CCAAT/enhancer-binding protein homologous protein （CHOP）. MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks， followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg^-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L^-1 were included in study （n=48）. The rats were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg^-1·d^-1）， a high-dose MHGW group （2.5 g·kg^-1·d^-1）， and a low-dose MHGW group （1.25 g·kg^-1·d^-1）. Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks， the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue （LFB） staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species （ROS） levels. Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to evaluate the expression of p-IRE1α protein， IRE1α mRNA， CHOP protein， and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group， the model group showed elevated serum ROS levels （P<0.01）. In contrast， the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group （P<0.01）. The sciatic nerve of the model group showed pathological changes compared with that in the normal group， while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group （P<0.01）. However， the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group （P<0.05， P<0.01）. Furthermore， compared with the normal group， the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve （P<0.01）， while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group （P<0.01）. ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA， thereby preventing and treating peripheral neuropathy in diabetes.

ObjectiveTo investigate the effect of modified Huangqi Guizhi Wuwutang （MHGW） on the protein and mRNA expression of B-cell lymphoma-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase-12 （Caspase-12） related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes. MethodAnimal experiments were conducted. A diabetes model was induced in sixty male sprague-dawley （SD） rats by feeding on a high-sugar and high-fat diet combined with streptozotocin （STZ） intraperitoneal injection. Rats with random blood glucose levels ≥ 16.7 mmol·L^-1 for three consecutive days were considered to have successfully developed diabetes. Forty-eight rats that successfully developed diabetes were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg^-1·d^-1）， a high-dose MHGW group （2.5 g·kg^-1·d^-1）， and a low-dose MHGW group （1.25 g·kg^-1·d^-1）， with 12 rats in each group. Another 10 rats were assigned to the normal group. Body weight and random blood glucose levels of the rats were monitored. At the end of a 16-week intervention period， the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system. The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultCompared with the normal group， the model group showed a significant decrease in body weight （P<0.01） and a significant increase in random blood glucose levels （P<0.01）. After a 16-week intervention， compared with the model group， the high-dose MHGW group exhibited a significant increase in body weight （P<0.05）， while there were no statistically significant differences in body weight changes among the other treatment groups. Random blood glucose levels significantly decreased in all treatment groups （P<0.01）. After 16 weeks of intervention， compared with the normal group， the model group had significantly reduced motor and sensory nerve conduction velocities （P<0.01）. Compared with the model group， all treatment groups showed significant increases in motor and sensory nerve conduction velocities （P<0.05， P<0.01）. The expression of Bax and Caspase-12 proteins in the sciatic nerve cells was significantly elevated in the model group compared with that in the normal group （P<0.01）. In contrast， all treatment groups showed significant reductions in the expression of Bax and Caspase-12 proteins in the sciatic nerve cells as compared with that in the model group （P<0.01）. The expression of Bax and Caspase-12 mRNA in the sciatic nerve cells significantly increased in the model group compared with that in the normal group （P<0.01）. Compared with the model group， the α-lipoic acid group and the high-dose MHGW group showed significant reductions in the expression of Bax mRNA in the sciatic nerve cells （P<0.05， P<0.01）， while the low-dose MHGW group showed a decreasing trend in the expression of Bax mRNA. The expression of Caspase-12 mRNA in the sciatic nerve cells significantly decreased in all treatment groups （P<0.01）. ConclusionMHGW may improve and repair sciatic nerve damage in diabetes rats by inhibiting sciatic nerve cell apoptosis.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective: To analyze cases in different groups of DRGs mortality risk ranking regarding overall medical dispute cases of the hospital from 2012 to 2017, and to study various groups of such ranking for these disputes as faced by different clinical departments, for the purpose of targeted intervention into medical risk exposures. Methods: Inpatient medical dispute cases in 2012-2017 period were selected, and classified into the various mortality groups by the standards and definition of BJ-DRGs. These data were used to calculate medical dispute incidence in each group, and analyze the difference between internal medicine and surgery departments. Results: Medical disputes of the hospital were mostly found in case groups of mortality free and those of low mortality risks, accounting for 66% of the total cases. This figure was the highest in surgical departments, having a percentage as high as 72%, and the CMI values of these cases were low as well (0.765 and 1.416 respectively). Conclusions As case groups of mortality free and low risks tend to attract disputes, the hospital is recommended to enhance the risk awareness and training of its medical staff and key medical regulations.

Objective To explore the clinical value of easy access optimization treatment for patients with acute upper gastrointestinal hemorrhage.Methods A total of 132 patients who suffered from upper gastrointestinal hemorrhage ( UGIH) were selected as control group in our emergency department three years before green channel, and 183 patients with UGIH were selected as experimental group during period of green channel.The control group just received traditional emergency treatment while the experimental group was given emergency easy access scheme, and the length of hospitalization, rate of operation, rehaemorrhagia and rate of recovered and discharged were compared.Results Patients who accessed treatment by green channel stayed in the hospital for (7.8 ±2.41) days and cost (4 426.5 ±297.51) Yuan averagely.Those of experimental group was lower than control group (t=3.102,20.843, respectively;P<0.05).The volume of blood transfusion, number of operational patient, rehaemorrhagia, cured patients were (384.9 ±39.7) ml,1 case (0.5%), 2 cases (1.1%) and 181 cases (99.5%),respectively, which were better than those of the control group ( t/χ2 =15.445, 8.347, 4.857, 11.174, respectively;P<0.05).Conclusions The green channel not only reduces the length of hospitalization, expense, patient′s trauma, fatality rate and complication, but also enhances cured rates.It is worthy to popularize in clinical.

Peking University Third Hospital is one of the first hospitals for experiments in clinical pathway selected by the Ministry of Health,which keeps optimizing the clinical pathway management mechanism and function of information system in its 4-year practice.This article described the combination strategy of clinical pathway management and information system applications,in terms of reasonable design of the management plan,standardized clinical pathway,strengthened execution control and improvement of the quality control.The purpose is to balance the relationship between clinical pathway management norms and user-friendliness of the system,enhance rationality and feasibility,improve efficiency and provide high-quality service to ensure medical safety.

Objective: To investigate the effects of hepatitis B virus (HBV) X protein (HBx) on the expression of tumor necrosis factor-α (TNF-α) in glomerular mesangial cells (GMCs) and the underlying intracellular signal pathways. Methods: The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs. HBx expression in the transfected GMCs was assessed by Western-blot. TNF-α protein and mRNA were assessed by ELISA and semi-quantitative RT-PCR, respectively. Three kinase inhibitors-U0126, an inhibitor of extracellular signal-regulated kinases (ERKs);lactacystin, an inhibitor of nuclear factor-κB (NF-κB);and SB203580, a selective inhibitor of p38 MAP kinase (p38 MAPK) were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-αexpression in transfected GMCs. Results:A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h, which was not affected by any of those kinase inhibitors mentioned above. A similar increase in the expression of both TNF-αprotein and mRNA was also observed at 36 h and 48 h, which was significantly decreased in the presence of U0126 or lactacytin, but not SB203580. Conclusions:HBx upregulates TNF-αexpression in cultured GMCs, possibly through ERKs and NF-κB pathway, but not p38 MAPK pathway.

Objective To investigate the clinical features, risk factors, diagnose, treatments and prognosis of patients with hepatitis B virus (HBV)-related liver failure complicated with invasive pulmonary aspergillosis (IPA). Methods A case-control study was performed to retrospectively analyze the clinical data of 43 patients with HBV-related liver failure complicated with IPA. A cohort of 43 patients with HBV-related liver failure complicated with bacterial infection only was analyzed at the same time and another cohort of 43 patients with HBV-related liver failure without any infections served as the control group. Results Compared with the control group, patients with infection had lower platelet counts and prothrombin activity, higher scores of model for end-stage liver disease (MELD), especially the patients with IPA (F=42.43,13.69,14, 22, all P＜0.01). And the similar results were observed in patients with IPA group before and after Aspergillus infection (F= 12.09,14.52,-16.74, all P＜0.01). Furthermore, the annual mortality was 100. 0% in patients with IPA,which was higher than that of patients complicated with bacterial infection only; and both groups were higher than control group of patients without infection. The statistic results showed that patients with longer length of stay, more antibiotics usage, and more invasive procedures were all risk factors of HBV-related liver failure complicated with IPA. Conclusions Conditions of patients with HBV-related liver failure deteriorate rapidly after complicated with IPA and patients have higher mortality and poorer prognosis.Therefore, it will be effective to enhance the recognition of the early clinical manifestations, and make diagnosis timely and treat with potent anti-fungal therapy to improve their survival.

BACKGROUND: External preparations treatment of fractures in traditional Chinese medidne are mostly ordinary hard-paste, cream, ointment, which lack of modernized traditional Chinese medicine transdermal delivery systems, and the treatment has poor drug absorption and simple process. The treating procedure needs to be used repeatedly, which would affect fracture external fixation and lead to unsatisfactory therapeutic effect. In this Paler, the extemal treatment of traditional Chinese medidna was combined with advanced micro-nano-technology to develop a new medical complex functional materials-micron traditional Chinese medicine functional lining material, which is an organic combination of diaplasis, fixation and local drug remedy, which provides a better treatment for fractures. OBJECTIVE: To explore the effect of micron tradifional Chinese medicine functional lining material on the healing of fracture in rabbits, METHODS: After model preparation, rabbits were randomly divided into 4 groups: rabbits in the micron group were treated with micron traditional Chinese medicine functional lining material plus plaster external fixation; those in the traditional Chinese medidna control group were treated with ordinary Chinese medicine functional material plus plaster extemal fixation; those in the lining material control group were treated with ordinary lining material added plaster extemal fixation; those in the natural healing control group had no special treatments. The effect of fracture healing was evaluated by X-ray at 2, 4 and 6 weeks after modeling. The serum concentration of alkaline phosphatase, calcium and phosphorus was detected respectivaly before modeling and at 2, 4 and 6 weeks after modeling. RESULTS AND CONCLISION: ①X-rap examination:After 6 weeks the external was almost copletly absorbed and medullary cavity was completely recanalizad in the micron group, while fracture line disappeared and the external callus began to be absorbed and medullary cavity was not recanalized in the traditional Chinese medidne control group. Additionally, there were case of non-union stump hardening in natural healing group. ②Serum biochemistry:The activity of alkaline phosphatase reached a peak after 2 weeks in micron group, which was 2 weeks ahead of time compared with that in traditional Chinese medicine control group. And the peak concentration of alkaline phosphatase in micron group was higher than other groups. After 4 weeks serum calcium concentration started to fall significantly and phosphorus concentration started to rise significantly in micron group, as was statistically significant compared with other groups. After 6 weeks serum calcium concentration in micron group had fallen to normal level, while that in other groups was higher than normal. And phosphorus concentration in micron group increased significantly, which was statistically significant compared with natural healing group. The results demonstrated that micron feature traditional Chinese medicine lining matedat can enhance the activity of alkaline phosphatase, decrease the serum concentration of calcium and increase the serum concentration of phosphorus and the product of calcium and phosphorus, therefore, promote the healing of fracture, It shows that micron traditional Chinese medicine functional lining matedal plays a stronger effect on promoting the healing of fracture than that of ordinary Chinese medicine functional lining material.

The X gene of HBV encodes a 17-KD protein, termed HBx, which has been shown to function as a transcriptional trans-activator of a variety of viral and cellular promoter/enhancer elements. The aim of this study was to investigate the effect of HBx on gene expression of interleukin (IL)-1β and IL-6, and proliferation of rat mesangial cells in vitro. The X gene of HBV was amplified by PCR assay, and inserted into the eukaryotic expression vector pCI-neo. The structure of recombinant pCI-neo-X plasmid was proved by restrict endonuclease digestion and sequencing analysis. pCI-neo-X was transfected into cultured rat mesangial cell line in vitro via liposome. HBx expression in transfected mesangial cells was detected by Western blot. The IL-1β and IL-6 mRNA expression in those cells was assayed by semiquantitative RT-PCR. Mesangial cell proliferation was tested by MTT. The results showed that HBx was obviously expressed in cultured mesangial cell line at 36th and 48th h after transfection. The expression of IL-1β and IL-6 mRNA was simultaneously increased. The cell proliferation was also obvious at the same time. It was concluded that HBx gene transfection could induce IL-1β and IL-6 gene expression and mesangial cell proliferation. HBx may play a critical role in mesangial cell proliferation through upregulation of the IL-1β and IL-6 gene expression.