[New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients].

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

[Comparison of hip offset and rotation center reconstruction between robot-assisted and manual total hip arthroplasty].

Objective: To compare the differences of hip offset and rotation center reconstruction between robot-assisted and manual total hip arthroplasty (THA). Methods: Patients underwent robot-assisted and manual THA from May to September of 2020 in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study. The patients included 27 patients (28 hips) in robot-assisted THA (rTHA) group and 29 patients (31 hips) in manual THA (mTHA) group. In rTHA group, there were 16 males and 11 females, with a mean age of (59±13) years. In mTHA group, there were 18 males and 11 females, with a mean age of (63±14) years. Basic information, including gender, age, body mass index (BMI), diagnosis and functional scoring etc, were recorded. In rTHA group, Mako robot system was used for preoperative planning, intraoperative real-time location and navigation. In mTHA group, traditional preoperative template design and surgical procedure were carried out. Operation time and functional scoring were compared postoperatively. Femoral offset, acetabular offset, global offset, rotation center changes in vertical and horizontal directions were measured on pelvis X-ray and analyzed. The correlation between intraoperative feedback of global offset change in robot system and postoperative measured global offset were analyzed. Results: Operation time in rTHA group was (80±10) min, which was statistically longer than that in mTHA group ((58±18) min, P<0.001). With 6 months' follow-up, the Harris scoring in rTHA group was 94.9±2.8, which was statistically higher than that in mTHA group (93.1±2.8, P=0.017), however there was no statistic difference in WOMAC scoring between rTHA and mTHA group (7.0±3.8 vs 7.1±2.4, P=0.840). Absolute global offset change within 5 mm, 5-10 mm and lager than 10 mm were 71.4%(20/28), 28.6%(8/28) and 0 in rTHA group, which were 45.2%(14/31), 29.0%(9/31) and 25.8%(8/31) in mTHA group (all P<0.05). A positive relation was found between intraoperative feedback of global offset change in robot system and postoperative measured global offset in rTHA group (r=0.77, P<0.001). It was found that rotation center changes concentrated in outer upper quadrant in both groups, and rotation center change in rTHA group concentrated mainly in the area less than 10 mm, however, rotation center change in mTHA group was more dispersive compared with rTHA group. Conclusion: rTHA may accurately reconstruct hip offset and rotation center, intraoperation feedback of global offset change may be an effective reference.

[Quality of life and related factors in patients with interstitial cystitis/bladder pain syndrome].

OBJECTIVE: To evaluate the quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS), to compare the difference between IC/BPS and overactive bladder (OAB) pain syndrome, and to explore the related factors affecting the quality of life of IC/BPS patients. METHODS: The demographic data of female outpatients with IC/BPS in Beijing Hospital and other medical centers in China were collected. The quality of life of the patients was investigated by multi-angle questionnaires and compared with the data of OAB patients. According to the influence degree of quality of life, the patients with IC/BPS were divided into mild-moderate group and severe group. RESULTS: In this study, 109 patients with IC/BPS were included. The average age was (46.4±14.3) years and the average course of disease was (39.4±51.6) months. Compared with the OAB patients, the patients in IC/BPS group had a longer average course of disease (P=0.008), a lower proportion of the patients of first visit for the disease (P < 0.001), a higher score of the American Urological Association symptom index (AUA-SI) (P < 0.001), a lower body mass index (BMI) ratio (P=0.016), and a lower incidence of constipation (P=0.006). IC/BPS had the greatest impact on family life, followed by social activity. The score of IC/BPS related symptoms on family life was significantly higher than that of the OAB group (P=0.003). The top three symptoms of the IC/BPS patients were pain (45%), frequency (28%) and urgency (17%). The score of quality of life in the IC/BPS patients was significantly higher than that in the OAB patients (P < 0.001). Caffeine intake (P=0.034) and constipation (P=0.003) might be the factors influencing the quality of life of the patients with IC/BPS. CONCLUSION: IC/BPS has a great influence on the quality of life of patients. Caffeine intake and constipation may be related factors affecting the quality of life of patients with IC/BPS. Urologists should recommend changes in diet and lifestyle to reduce symptoms and improve the patients' quality of life.

[Treatment outcome of 100 patients with hepatoblastoma based on a new risk stratification].

Objective: To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients. Methods: A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk. The patients at very low risk were treated with surgery only and followed-up. The patients at very low risk were treated with C5V(Cisplatin+ 5-Fluroracil+ Vincristine) regimen for 4 courses. The patients at intermediate risk were treated with C5VD(Cisplatin+ 5-Fluroracil+ Vincristine+ Doxorubicin)regimen before and after surgery for 6-8 courses. The patients at high risk were treated with C5VD and IIV (ifoshamide+ irinotecan+ vincristine) alternately before and after surgery for 8 courses. Results: One hundred patients were stratified into extremely low-risk, low-risk, medium-risk and high-risk groups for 2, 10, 51 and 37 cases, respectively. Eighty three cases had evaluable lesions before chemotherapy. Among them, 65 patients achieved partial remission, stable disease and progressive disease were observed in 10, and 8 cases, respectively, with a response rate of 78.3%. During a median follow-up of 20 months, 30 patients experienced tumor relapse or progression, and 27 of them died. The 2-years progression-free survival (PFS) and overall survival (OS) rates were 69.2% and 72.0%, respectively. The 2-years PFS rates of patients with extremely low risk, low risk, medium risk and high risk were 100%, 88.9%, 75.3% and 43.2%, respectively. The 2-years OS rates were 100%, 100%, 81.0% and 44.8%, respectively. Conclusions: The novel HB risk classification is simple and feasible. With active comprehensive treatment, patients at extremely low-, low- and medium-risk have excellent outcomes. The survival rate of high-risk HB patients remains to be improved, and new treatment strategies need to be explored.

LncRNA MT1JP inhibits the malignant progression of hepatocellular carcinoma through regulating AKT.

OBJECTIVE: The purpose of this study was to investigate the expression profile of long non-coding RNA (lncRNA) MT1JP in hepatocellular carcinoma (HCC), and to explore the relationship between its expression level and the clinical indicators, as well as the prognosis of HCC patients. PATIENTS AND METHODS: In this study, the expression level of MT1JP in 45 pairs of tumor tissue specimens and paracancerous ones collected from HCC patients were examined through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) method, and the interplay between MT1JP expression and clinical indicators, as well as the prognosis of HCC patients, was also analyzed. Meanwhile, the expression of MT1JP in HCC cell lines was further verified by qRT-PCR. In addition, MT1JP overexpression model was constructed using lentivirus in HCC cell lines (Hub7 and HepG2), and then, Cell Counting Kit-8 (CCK-8), cell colony formation assay, and flow cytometry were performed to examine the impact of MT1JP on the HCC cell functions. Additionally, whether MT1JP exerts its biological characteristics through protein kinase B (AKT) was finally explored. RESULTS: In this experiment, qRT-PCR results showed that the expression level of lncRNA MT1JP in tumor tissues of HCC patients was remarkably lower than that in adjacent tissues, and the difference was statistically significant. Meanwhile, compared with patients with high expression of MT1JP, patients with low expression of MT1JP had a higher pathological staging and a lower overall survival rate. In addition, overexpression of MT1JP remarkably attenuated the proliferation ability of HCC cells but enhanced cell apoptosis rate at the same time. Finally, Western blot results revealed that the overexpression of MT1JP may markedly reduce the AKT expression, thereby suppressing the malignant progression of HCC. CONCLUSIONS: LncRNA MT1JP expression is remarkably decreased in HCC tumor tissue samples, which is associated with pathological stage and poor prognosis of HCC patients. In addition, MT1JP may inhibit the malignant progression of HCC by downregulating AKT.

miR-34a and miR-125a-5p inhibit proliferation and metastasis but induce apoptosis in hepatocellular carcinoma cells via repressing the MACC1-mediated PI3K/AKT/mTOR pathway.

microRNA-34a (miR-34a) and microRNA-1251-5p (miR-125a-5p) were considered as tumor suppressors in hepatocellular carcinoma (HCC). Nevertheless, the modulatory mechanisms of miR-34a and miR-125a-5p in HCC haven't been completely understood. The levels of metastasis-associated with colon cancer 1 (MACC1) and miRNAs (miR-34a and miR-125a-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of associated proteins were detected by western blot assay. Cell proliferation and metastasis were examined via Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Cell apoptosis was measured through flow cytometry. The effect of MACC1 on HCC in vivo was explored via xenograft assay. Dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay were implemented to explore the target correlation. The expression of MACC1 was upregulated in HCC tissues and cells. Knockdown of MACC1 inhibited proliferation and metastasis but expedited apoptosis of HCC cells and the repression of tumor growth in vivo was evoked by MACC1 downregulation. Both miR-34a and miR-125a-5p directly targeted MACC1 and repressed the expression of MACC1 in HCC cells. Overexpression of miR-34a or miR-125a-5p restrained cell proliferation and metastasis while induced apoptosis by downregulating MACC1 in HCC cells. miR-34a and miR-125a-5p repressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway via reducing MACC1 in HCC cells. miR-34a and miR-125a-5p refrained proliferation and metastasis while motivated apoptosis in HCC cells through the PI3K/AKT/mTOR pathway by repressing MACC1. miR-34a and miR-125a-5p might be splendid biomarkers in the therapeutic strategies for HCC.

[The clinical efficacy of arthroscopic combined with dual-plane high tibial osteotomy in the treatment of anterior cruciate ligament injury combined with varus deformity of knee joint].

Objective: To explore the short-term effectiveness of arthroscopic combined with dual-plane high tibial osteotomy in the treatment of anterior cruciate ligament injury combined with varus deformity of knee joint. Methods: A retrospective study was performed on 17 patients with anterior cruciate ligament injury combined with varus deformity of knee joint who underwent arthroscopic combined with dual-plane high tibial osteotomy at Department of Bone and Joint, the Affiliated Hospital of Southwest Medical University from January 2017 to June 2018.There were 11 males (11 knees) and 6 females (6 knees), aged 41.3 years (range: 32 to 49 years) .During the surgery, the weight bearing line of lower extremity was set to 62.5% position of the tibial plateau on coronal plane. The tibial slope was adjusted to the normal range on sagittal plane, and anterior cruciate ligament was reconstructed to improve the stability of knee joint.At final follow up, full length weight bearing X ray was used to evaluate the position of weight bearing line, femoral tibial angle and tibial slope pre- and post-operatively.The Lysholm scores, Hospital for Special Surgery score, Tegner knee activity scores and International Knee Documentation Committee (IKDC) scores were used to estimate knee joint function, while the Lachman test, KT-1000 side-to-side difference and pivot-shift test were used to estimate the knee joint stability. Results: The patients were followed up for 1.8 years(range:1.2 to 2.5 years). No complication such as infection, deep vein thrombosis, graft failure, nonunion or delayed union was observed.The weight bearing line was corrected from (28.48±2.24)% preoperatively to (57.43±1.02)% postoperatively (t=46.80, P=0.00) .The femoral tibial angle was improved from (172.31±3.37) ° preoperatively to (178.91±1.34) ° postoperatively(t=10.46, P=0.00). The tibial slope was decreased from (14.29±1.26) ° preoperatively to (9.31±0.79) ° postoperatively (t=24.59, P=0.00) . The KT-1000 side-to-side difference decreased from (7.95±1.19) mm preoperatively to (1.79±0.49)mm postoperatively(t=18.34, P=0.00). At the last follow-up, Lysholm score, Hospital for Special Surgery score, Tegner score, and the IKDC knee evaluation score of patients showed significant improvement from preoperative(P<0.05). Conclusion: Arthroscopic combined with dual-plane high tibial osteotomy can get a good short term efficacy in the treatment of anterior cruciate ligament injury combined with varus deformity of knee joint which can significantly improve the alignment of lower extremity and knee joint stability.

Down-regulation of hsa_circ_0092125 is related to the occurrence and development of oral squamous cell carcinoma.

Circular RNA plays an important role in regulating tumour development and progression and can serve as a biomarker for cancer. This study was performed to investigate the clinical significance of hsa_circ_0092125 expression in oral squamous cell carcinoma (OSCC). The expression of hsa_circ_0092125 in OSCC tissues and cell lines was determined by reverse transcription-quantitative PCR analysis. The association between hsa_circ_0092125 expression and clinicopathological data was determined by χ2 test. Overall survival (OS) curves were created using Kaplan-Meier survival analysis, and the differences were examined by log-rank test. Moreover, univariate and multivariate Cox analysis were employed to evaluate the risk factors of the OSCC prognosis. The expression of hsa_circ_0092125 was significantly down-regulated in OSCC tissues and cell lines. A low expression of hsa_circ_0092125 was associated with clinicopathological factors in OSCC patients, including tumour size, TNM stage, and lymph node metastasis. Kaplan-Meier survival analysis indicated that the OS time was shorter in OSCC patients with a lower hsa_circ_0092125 expression level than in those with a higher expression level. In addition, univariate and multivariate Cox analysis identified lower hsa_circ_0092125 expression, tumour size, TNM stage, and lymph node metastasis as independent risk factors for the OSCC prognosis. Thus, down-regulated expression of hsa_circ_0092125 might serve as a biomarker of the OSCC prognosis.

[Functional and supraomohyoid neck dissection in stage cN0/N1 oral squamous cell carcinoma].

Objective: To evaluate the clinical effects of functional neck dissection (FND) and supraomohyoid neck dissection (SOND) in patients with cN0/N1 oral squamous cell carcinoma (OSCC). Methods: A total of 210 patients with stage cN0/N1 OSCC underwent FND and SOND between January 2012 and May 2015 were retrospectively reviewed, among which, 147 patients were male and 63 were female, with an age range of 23-82 years and mean age of (62.2±10.2) years. There were 112 and 98 patients in FND and SOND groups, respectively. The follow-up data included cervical lymph node metastasis, movement of shoulder joint, great auricular nerve function, recurrence rate of cervical lymph nodes. Results: There was no significant difference in gender, age, tumor location, T stage, N stage, histological grades between the two groups (all P>0.05). Compared to patients in FND group, the activities of shoulder joint and earlobe numbness improved significantly in SOND group. Of the 210 patients, 17 patients (8.1%) had cervical recurrence, with 9 patients (8.0%) in FND group and 8 patients (8.2%) in SOND group. No significant difference was observed for neck recurrence between the two groups (P=0.973). Conclusion: SOND can be safely performed in cN0 or cN1 OSCC patients, which avoids major complications of FND, and improves postoperative quality of life in those patients.

[Relevant molecular characteristics analysis on malignant transformation of interstitial cells induced by tumor stem cells in glioma microenvironment].

Objective: A variety of interstitial cells in tumor microenvironment (TME) based on glioma stem cells(GSC) have the function to promote malignant progression of tumors, but whether these interstitial cells have already undergone malignant transformation and their related molecular characteristics are still poorly understood. Methods: Human SU3-RFP glioma stem cells (GSC) stably transfected with red fluorescent protein (RFP) and interstitial cells from enhanced green fluorescent protein (EGFP) transgenic nude mice were co-cultured in vitro. SU3-RFP cells were also inoculated in different tissues of EGFP-Balb/c nude mice. Immortal EGFP(+) cells were monocloned either from co-culture cells in vitro, or from their xenografts in vivo. These immortal EGFP(+) cells were confirmed to bear characteristics of tumor cell via chromosomal analysis and tumorigenicity assay. Related molecular phenotypes of these cells were further detected through RT-PCR, flow cytometry and immunochemistry(IHC) techniques. Results: (1) Two EGFP(+) cell lines were obtained in vitro, and 5 EGFP(+) cell lines were obtained in vivo tumorigenic experiments. Seven EGFP(+) cell lines all have characteristics of self-renewal, heteroploid of chromosomes and 100% tumorigenicity. (2) Cell surface marker analysis showed cell origin of these cell lines were macrophages (tMΦ1 and tMΦ2 ), dendritic cells (tDC1 and tDC2), fibroblasts (tFB), oligodendrocytes (tOG) and BMSC cells (tBMSC), respectively. (3)All of these seven cell lines co-expressed Sca-1 and c-myc, and have Sox-2 or Nanog expression also, which suggest that they may bear molecular characteristics of mesenchymal stem cells or pluripotent stem cells. Conclusions: (1) Tumor stromal cells in TME have undergone malignant transformation, which is related to the tissue remodeling of TME by GSCs, and not limit to the specific type of their parasitic tissues. (2) Tumor cells originated from GSC and tumor interstitial cells, respectively, are two major types of tumor cells with different origins in glioma parenchyma, can not be simply regarded as tumor heterogeneity, transformed interstitial cells of TME may have the potential to serve as new targets for target diagnosis and therapy.

[Experimental studies on correlation between nucleolus spindle-related protein 1 and the malignant progression and prognosis of human glioblastoma multiforme].

Objective: To investigate the correlation between nucleolus spindle-related protein 1 (NUSAP1) and malignant progression and prognosis of human glioblastoma multiforme (GBM). Methods: RT-PCR and immunohistochemical technique were applied to analyze NUSAP1 expression level in GBM surgical specimens. Correlations between NUSAP1 expression and molecular classification and survival of patients with GBM were also investigated in TCGA database. The gene silencing technique was used to silence NUSAP1 expression in U87 cells, CCK-8 assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle changes, and in vivo tumorigenicity was evaluated after NUSAP1 silencing in tumor-bearing mice. Results: NUSAP1 expression level in GBM was higher than that in non-tumor brain tissue. Survival curve analysis showed that the survival time of GBM patients with high NUSAP1 expression decreased significantly (P<0.01). NUSAP1 expression was relatively lower in mesenchymal and neural molecular subtypes of GBM, when compared with the other two molecular subtypes. And it was closely related with specific genetic aberrations (such as PTEN loss and IDH1 mutation). Silencing NUSAP1 inhibited G2/M cell cycle progression of GBM cells, and inhibited cell proliferation both in vitro and in vivo. Conclusion: Expression of NUSAP1 is closely related to progress and prognosis of GBM, and can be a biomarker reflecting GBM prognosis and act as a therapeutic target with potential clinical application value.

Synthesis, crystal structure, and anti-breast cancer activity of a novel metal-porphyrinic complex [YK(TCPP)(OH)2·(solvents)x]

A novel heterometallic metal-porphyrinic framework (MPFs) built from Y and K ions as nods and meso-tetra(4-carboxyphenyl)porphyrin as linkers has been successfully synthesized and characterized. The single crystal X-ray diffraction indicated that this complex 1 exhibited a bilayered architecture of the porphyrins, which is seldom seen in MPFs. In addition, in vitro anticancer activity of complex 1 on three human breast cancer cells (BT474, SKBr-3 and ZR-75-30) was further determined.

Synthesis, crystal structure, and anti-breast cancer activity of a novel metal-porphyrinic complex [YK(TCPP)(OH)2·(solvents)x].

A novel heterometallic metal-porphyrinic framework (MPFs) built from Y and K ions as nods and meso-tetra(4-carboxyphenyl)porphyrin as linkers has been successfully synthesized and characterized. The single crystal X-ray diffraction indicated that this complex 1 exhibited a bilayered architecture of the porphyrins, which is seldom seen in MPFs. In addition, in vitro anticancer activity of complex 1 on three human breast cancer cells (BT474, SKBr-3 and ZR-75-30) was further determined.

Autophagy inhibition increased the anti-tumor effect of cisplatin on drug-resistant esophageal cancer cells.

The sensitivity of tumor cells to treatment can be affected by autophagy. The drug resistance of esophageal cancer cells against cisplatin occurs during the long period of chemotherapy drug treatment. This study was designed to observe the effect autophagy has on the occurrence of esophageal cancer cell drug resistance against cisplatin and investigate its molecular mechanism in order to provide new details and strategies for the clinical treatment of esophageal cancer, especially cisplatin treatment. The detection methods used in this study were 3-(4,5-dimethylthiazd-2-yl)-2,5-dipheny-ltetrazolium bromide (MTT) colorimetric assay, clone survival technique, small interfering RNA (siRNA) transfection, and Western blot. Autophagy is a protection mechanism of drug-resistant cells processed by cisplatin, and maintains the cell clone survival ability. Autophagy activation requires the involvement of Atg5 and Atg7.

[Survey of economic burden of hepatitis B-related diseases in 12 areas in China].

Objective: Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China, so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking. This study aimed to analyze the direct, indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China. Methods: The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study. All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases. The direct expenditure included direct medical cost and direct non-medical cost. The indirect expenditure, including work loss of patients and caregivers, were calculated by using human capital method for urban and rural populations in 12 areas. The intangible expenditure were reflected by willing to pay and stochastic tournament. The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis. Results: A total of 27 hospitals in 12 areas were included in the survey. A total of 4 718 cases were surveyed, the overall response rate was 77.7%. The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case, in which the highest proportion (61.2%) was medicine fees [10 365.10 yuan (RMB)]. The average direct expenditure and indirect expenditure were consistent with the severity of illness, which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively, with the ratio of 3.85 ∶ 1. The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)]. It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures. Among the average indirect expenditure, the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)]. The total direct and indirect expenditure was highest for liver transplantation, followed by severe hepatitis, hepatocellular carcinoma and decompensated cirrhosis, acute hepatitis B, compensated cirrhosis and chronic hepatitis B. The influencing factors for both direct and indirect expenditure were high hospital level, severity of hepatitis B, living in urban area, antiviral therapy, long hospitalization and monthly income of family. For average 3.74 outpatient visits and 1.51 hospitalization, the average annual direct, indirect and intangible expenditure for HB-related diseases were 30 135.30, 6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)], accounting for 37.3%, 7.7% and 55.0%, respectively. Of the annual direct medical expenditure [28 402.80 yuan (RMB)], which were much higher than non-medical expenditure [1 732.50 yuan (RMB)], hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)]. The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB), respectively. Of the annual intangible expenditure, the highest was that for primary hepatocellular carcinoma, followed by cirrhosis, chronic hepatitis B, severe hepatitis B, liver transplantation and acute hepatitis B. Conclusions: A heavy economic burden has been caused by HB-related diseases in China, and patients are more likely to rely on medical service rather than non-medical service. It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits. The influence of HB related diseases on mental health of the people can be reflected by an economics term, intangible expenditure.

Transcription Factors in Breast Cancer-Lessons From Recent Genomic Analyses and Therapeutic Implications.

Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways. A notable observation is that DB-TFs that mediate major oncogenic signaling (e.g., WNT, receptor tyrosine kinase (RTK), NOTCH, and HIPPO), which switch from default repression (signal OFF) to transcriptional activation (signal ON), are not altered in breast cancer. Instead, corepressors (e.g., pRb for E2F1 downstream of various proliferation signals) or upstream factors (e.g., APC and AXIN for TCF, downstream of canonical WNT signaling) are lost, or coactivators (e.g., NOTCH1/2 for CSL/RBPJk) are induced. In contrast, constitutive (MYC, TBX3) and signal-induced (TP53, FOXA1) DB-TFs that do not mediate default repression are directly altered in breast cancer. Some of these TFs have been implicated in the establishment of super-enhancers and positive transcriptional elongation. In addition, oncogenic transcription is induced by mutations affecting regulatory elements or chromatin conformation that create new TF-binding sites in promoters and enhancers of oncogenic genes to promote tumorigenesis. Here we review these diverse oncogenic alterations in TFs in BC and discuss implications for therapy.

Apoptosis, proliferation, and morphology during vein graft remodeling in rabbits.

Neo-intima development and atherosclerosis limit the long-term use of vein grafts for revascularization of ischemic tissues. Recently, studies have confirmed that proliferating cell nuclear antigen (PCNA) plays an important role in cell proliferation. Our research confirmed that 28 days after vein transplantation, PCNA expression increases significantly. Using rabbits, rather than rodents, for a more representative model of human vein grafts, we aimed to establish a time course of changes in cell proliferation and apoptosis using morphometric and immunohistochemical analyses, western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling, and transmission electron microscopy (TEM). The external jugular veins of 42 healthy purebred male New Zealand white rabbits were grafted onto their common carotid arteries. The rabbits were divided into seven groups, with vein grafts being harvested before surgery, and at 1, 3, 7, 14, 28, and 90 days afterwards. The extent of stenosis and apoptosis, PCNA protein levels, and TEM morphology were subsequently examined. Intimal thickness was slightly decreased 1 day following surgery, but then increased continuously until the 90th day. Western blot and immunohistochemistry both indicated lowered PCNA expression on day 1, although levels subsequently increased, peaking at 7 days post-surgery. After surgery, apoptosis was lowest on day 7, and remained low thereafter. TEM revealed signs of apoptosis as vein graft restenosis progressed. Proliferation and apoptosis co-occurred following grafting, indicating that both processes were involved in vein graft remodeling. Apoptosis levels were highest between days 1 and 3 after surgery, whereas proliferation culminated on the 7th day.

Transthoracic closure of atrial septal defect and ventricular septal defect without cardiopulmonary bypass.

The minimally invasive surgical transthoracic occlusion of an atrial septal defect (ASD) or a ventricular septal defect (VSD) is an increasingly widespread alternative treatment for congenital heart disease. The aim of this study is to summarize our clinical experience with minimally invasive surgical transthoracic occlusion of ASD and VSD without cardiopulmonary bypass (CPB). Between April 2011 and October 2012, 27 patients with ASD and 95 patients with VSD (78 men and 44 women) were considered for minimally invasive surgical transthoracic occlusion without CPB. A small infrasternal incision (2.0-4.0 cm) was made under general anesthesia, under transesophageal echocardiography (TEE) guidance; the ASD and VSD were closed by using an appropriate occluder; and TEE was performed simultaneously to demonstrate the position of the device, any residual shunting, or encroachment on the atrioventricular valve, coronary sinus, or aortic valve. Successful transthoracic occlusion was performed in all 122 patients without complications. No complications such as third-degree atrioventricular block and residual shunting occurred after the procedures. The ventilation time was 2.2 ± 1.2 h, and the average length of hospital stay was 4.7 ± 1.7 days. All patients received aspirin at 3 mg·kg(-1)·day(-1) (maximum 100 mg/day) 24 h after the procedure. Minimally invasive surgical transthoracic occlusion without CPB is a new treatment that has many advantages such as causing little trauma, promoting quick recovery, having less complications, and avoiding radiation damage. However, the appropriate selection of patients is still key to improving the success rate of the operation.

Effect of glycogen synthase kinase-3 inactivation on mouse mammary gland development and oncogenesis.

Many components of the Wnt/ß-catenin signaling pathway have critical functions in mammary gland development and tumor formation, yet the contribution of glycogen synthase kinase-3 (GSK-3α and GSK-3ß) to mammopoiesis and oncogenesis is unclear. Here, we report that WAP-Cre-mediated deletion of GSK-3 in the mammary epithelium results in activation of Wnt/ß-catenin signaling and induces mammary intraepithelial neoplasia that progresses to squamous transdifferentiation and development of adenosquamous carcinomas at 6 months. To uncover possible ß-catenin-independent activities of GSK-3, we generated mammary-specific knockouts of GSK-3 and ß-catenin. Squamous transdifferentiation of the mammary epithelium was largely attenuated, however, mammary epithelial cells lost the ability to form mammospheres suggesting perturbation of stem cell properties unrelated to loss of ß-catenin alone. At 10 months, adenocarcinomas that developed in glands lacking GSK-3 and ß-catenin displayed elevated levels of γ-catenin/plakoglobin as well as activation of the Hedgehog and Notch pathways. Collectively, these results establish the two isoforms of GSK-3 as essential integrators of multiple developmental signals that act to maintain normal mammary gland function and suppress tumorigenesis.