Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Effects of operating room nursing intervention on wound infection in patients undergoing ovarian cysts surgery: A meta-analysis.

We conducted this study aimed to explore the effect of operating room nursing intervention on wound infection in patients undergoing ovarian cysts surgery. A computer system was used to search PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, from database inception to October 2023, for randomised controlled trials (RCTs) on the application of operating room nursing intervention to ovarian cyst surgery. Literature that met the requirements was independently screened by two researchers, and data were extracted and assessed for literature quality. RevMan 5.4 software was applied for data analysis. Fifteen RCTs involving 1187 patients were finally included. The analyses revealed that, compared with routine nursing, the implementation of operating room nursing intervention had a significant advantage in reducing the incidence of wound infections (1.17% vs. 5.44%, odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.15-0.58, p = 0.0004) and postoperative complications (6.34% vs. 25.17%, OR: 0.20, 95%CI: 0.13-0.29, p < 0.00001), as well as being able to shorten the operative time (standardised mean difference [SMD]: -3.93, 95%CI: -5.67 to -2.20, p < 0.00001), hospital length of stay (SMD: -2.54, 95%CI: -3.19 to -1.89, p < 0.00001) and gastrointestinal recovery time (SMD: -1.61, 95%CI: -2.24 to -0.98, p < 0.00001) in patients undergoing ovarian cysts surgery. This study confirmed by meta-analysis that the operating room nursing intervention can significantly reduce the incidence of wound infection and complications, shorten the operative time, gastrointestinal recovery time, and hospital length of stay after ovarian cyst surgery.

[Difficulties and Confusion Concerning the Management of Hypertensive Disorders in Pregnancy--Interpretation of the Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy (2020)].

Hypertensive disorder in pregnancy is a disease with diverse clinical manifestations. Herein, we provided interpretations for "The Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy in China (2020 Edition)" and discussed the difficulties and confusion encountered in the management of hypertensive disorders in pregnancy in combination with clinical practice. Lowering blood pressure is the most important treatment and maintaining a stable target blood pressure can reduce damage to organ functions and is beneficial to fetal growth. When applying magnesium sulfate, attention should be paid to the indications and contraindications. Attention should be paid to hypoproteinemia in patients tested positive for proteinuria. There should be dynamic evaluation of the functions of maternal vital organs, fetal growth and development, fetal well-being and intrauterine safety, and determination of the appropriate timing of the termination of pregnancy, so as to ensure maternal and fetal safety. Attention should be paid to maternal high-risk factors, if early prediction and prevention are to be accomplished in order to reduce the incidence and severity of the disease.

Prognostic role of the recepteur d'origine nantais (RON) expression in primary high-grade osteosarcoma.

BACKGROUND: Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma. METHODS: Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ2 test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ2 test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan-Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients. RESULTS: The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P < 0.001) and osteosarcoma cell lines. Moreover, immunohistochemical high expression of RON was associated with a poor response to chemotherapy (P = 0.032) as well as worse progression-free (P = 0.003) and overall (P < 0.001) survival of osteosarcoma patients. Multivariate analysis revealed that high expression of RON was independently associated with reduced progression-free (P = 0.027, HR = 2.31) and overall survival (P = 0.004, HR = 5.06) time of osteosarcoma patients. CONCLUSIONS: The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.

Clinicopathological and prognostic value of NADPH oxidase 2 (NOX2) in primary osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, particularly among children and adolescents, and the prognosis of osteosarcoma patients remains poor. The NADPH oxidase 2 (NOX2) has been found over-expressed in several human cancers, and closely associated with poor prognosis. Meanwhile the role of NOX2 in osteosarcoma patients has not been reported. This study aimed to investigate the clinicopathological and prognostic significance of NOX2 in osteosarcoma patients. METHODS: Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of NOX2 in 55 primary osteosarcoma specimens and in 20 non-neoplastic bone tissue specimens. The correlations between NOX2 expression and clinicopathological parameters were analysed by using the χ2 test or Fisher's exact test. Disease free survival and overall survival of osteosarcoma patients were assessed by using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: NOX2 was over-expressed significantly in osteosarcoma compared with that in non-neoplastic bone tissue, and correlated with progression free survival (P < 0.001) and overall survival (P < 0.001). The over-expression of NOX2 was associated with tumor size (P < 0.001), tumor location (P < 0.001). The Cox analysed shown that the over-expression of NOX2 was predicted to be worse PFS (hazard ratio (HR) = 4.10, P = 0.004) and OS (hazard ratio (HR) = 3.50, P = 0.010) time in osteosarcoma patients. CONCLUSIONS: The results of our study suggest that the over-expression of NOX2 is related to adverse clinical outcome, and can be viewed as an independent prognostic marker in osteosarcoma. Further research is required to verify the predictive value of NOX2 in osteosarcoma patients.

Initial-onset symptoms of preeclampsia and their relation to pregnancy outcomes.

Preeclampsia (PE) is a serious gestational idiopathic hypertensive disease, threatening both maternal and foetal safety. As a systemic disease, the initial-onset symptoms (IOSs) and clinical manifestations of PE can vary widely from patient to patient. However, a lack of evidence-based data on IOS and their relationship to their corresponding clinical features and pregnancy outcomes persists. We hypothesised that there would be a significant difference between the morbidity time, subsequent organ dysfunction and the status of mother and foetus in PE patients with different IOS. Moreover, early identification of the characteristics of the PE patients with different IOS could improve pregnancy outcomes through individualised prevention or intervention. This study aimed to analyse maternal and foetal condition and pregnancy outcomes of PE patients with different IOS, and to explore the disease progression and characteristics of maternal and foetal outcomes for different IOS, so as to provide the basis for future maternal and foetal monitoring of PE patients.Impact statementWhat is already known on this subject? In 2013, the American College of Obstetricians and Gynecologists revised their definition of PE, sparking a heated debate. Subsequently in 2015, China updated its guidelines to define PE as hypertensive pregnancy accompanied by involvement of any other organ or organ system, to include the heart, lungs, liver and kidneys, among others. However, IOS can be varied in PE, so the maternal management and foetal monitoring should be classified through different IOS. No evidence-based data on IOS in PE patients exist.What the results of this study add? Significant differences in mean morbidity times and mean delivery times were demonstrated among patients with different IOS; medians of the interval from morbidity to delivery were between 4 and 6 weeks. Significant differences in laboratory values were found in patients with different IOS. In patients that did not present with proteinuria as an IOS, 89.1% experienced proteinuria following diagnosis. Patients with the most severe complications presented with hypertension as an IOS. Follow-up visits demonstrated different foetal weight medians.What the implications are of these findings for clinical practice and/or further research? IOS could be an indicator to help evaluate the potential for different maternal and foetal complications and PE outcomes. Moreover, the duration of treatment for PE maybe 4-6 weeks.

Clinicopathological and prognostic values of ErbB receptor family amplification in primary osteosarcoma.

Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.

Clinicopathological and prognostic values of fibronectin and integrin αvß3 expression in primary osteosarcoma.

BACKGROUND: Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvß3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvß3 in osteosarcoma. METHODS: Immunohistochemistry and western blotting were used to detect the expression of FN and αvß3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and αvß3 with the clinicopathological features of osteosarcoma patients were analyzed using the χ2 test and Fisher's exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index. RESULTS: FN (P < 0.05) and αvß3 (P < 0.05) were overexpressed in osteosarcoma specimens compared with osteochondroma specimens. High FN expression was associated with a poor response to chemotherapy (P = 0.001) and poor disease-free (P < 0.001) and overall (P < 0.001) survival. High expression of αvß3 was linked to an advanced surgical stage (P = 0.028), a poor response to chemotherapy (P = 0.002), and both poor disease-free survival (P < 0.001) and overall survival (P < 0.001). FN and αvß3 co-expression were associated with sex (P = 0.011), an advanced surgical stage (P = 0.013), and a poor response to chemotherapy (P = 0.002). Moreover, high expression of both proteins can serve as an independent prognostic value for reduced survival time in osteosarcoma patients. CONCLUSIONS: The results of this study suggest that FN and αvß3 expression is associated with an unfavorable clinical outcome of osteosarcoma, and these molecules may constitute attractive therapeutic targets for osteosarcoma treatment. To improve the survival of osteosarcoma patients, further investigations are required to clarify their prognostic values in a larger population.

Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

BACKGROUND: The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. RESULTS: LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). CONCLUSIONS: Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

[Guilu Erxian Glue Induced Osteogenic Differentiation of BMMSCs and Its Effects on Wnt Signal Pathway].

Objective To observe the effects of Guilu Erxian Glue (GEG) containing serum on osteogenin differentiation of bone marrow mesenchymal stem cells (BMMSCs) and Wnt signal pathway related factors. Methods Totally 100 three months old female SD rats had their bilateral ovaries excised peritoneally They were divided into the low, middle, high GEG groups, and the blank control group by random digit table, 25 in each group. The dose of GEG was calculated according to body surface area, and GEG containing serum was administered by gastrogavage for 7 successive days. Blood was collect- ed by abdominal aorta to prepare drug containing serum. F3 passage BMMSCs of 1-month SD rats were i- solated by whole bone marrow adherent method, and cultured in vitro for 3 passages. The cell surface markers (CD45 and CD90) of F3 passage were detected by flow cytometry (FCM). BMMSCs were trea- ted with different concentrations GEG containing serum for 72 h. Then the cell cycle was determined by FCM, and the proliferation index calculated. The optimal intervention concentration was determined. Then F3 passage BMMSCs were divided into four groups, i.e., the fetal bovine serum (FBS) group, the blank control group, the GEG group, the classical induction group. After they were treated with corresponding medium for 21 days, BMMSCs were dyed with alizarin red staining (ARS) to observe their osteogenin dif- ferentiation. mRNA expressions of alkaline phosphatase (ALP) and osteocalcin (OC) of BMMSCs were detected by RT-PCR. mRNA and protein expressions of Wnt5a, ß-catenin, and lymphoid enhancer factor- 1 (Lef-1) were detected by RT-PCR and Western blot. Results The ratio of CD45 positive expression was 1. 46% ?0. 23%, and the ratio of CD90 positive expression was 96. 97% ±3. 21%. Middle EGE contai- ning serum (10%) could significantly stimulate the proliferation of BMMSCs. In ARS citrus red calcium nodules could be seen in the GEG group and the classical induction group. Compared with the FBS group and the blank control group, mRNA expressions of OC and ALP were up-regulated, mRNA and protein expressions of Wnt5a and p-catenin were up-regulated in the GEG group and the classical induction group (P<0. 05). Compared with the FBS group, the blank control group, and the classical induction group, mRNA and protein expressions of Lef-1 were up-regulated in the EGE group (P <0. 05). Compared with the FBS group and the blank control group, protein expressions of Lef-1 increased in the classical induc- tion group (P <0. 05). Conclusions GEG containing serum had the functions of stimulating the prolifera- tion of BMMSCs, and inducing the osteogenic differentiation of BMMSCs. Its mechanism might be possi- bly related with regulating Wnt signal pathway related factors.

Heme oxygenase-1 promotes neuron survival through down-regulation of neuronal NLRP1 expression after spinal cord injury.

BACKGROUND: Understanding the mechanisms underlying neuronal death in spinal cord injury (SCI) and developing novel therapeutic approaches for SCI-induced damage are critical for functional recovery. Here we investigated the role of heme oxygenase-1 (HO-1) in neuroprotection after SCI. METHODS: Adeno-associated virus expressing HO-1 was prepared and injected into rat spinal cords before SCI model was performed. HO-1 expression, inflammasome activation, and the presence of inflammatory cytokines were determined by quantitative polymerase chain reaction, immunohistological staining, immunoblot, and immunoprecipitation. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. The hindlimb locomotor function was evaluated for extent of neurologic damage. In an in vitro model, hydrogen peroxide was used to induce similar inflammasome activation in cultured primary spinal cord neurons, followed by evaluation of above parameters with or without transduction of HO-1-expressing adeno-associated virus. RESULTS: Endogenous HO-1 expression was found in spinal cord neurons after SCI in vivo, in association with the expression of Nod-like receptor protein 1 (NLRP1) and the formation of NLRP1 inflammasomes. Administration of HO-1-expressing adeno-associated virus effectively decreased expression of NLRP1, therefore alleviating NLRP1 inflammasome-induced neuronal death and improving functional recovery. In the in vitro model, exogenous HO-1 expression protected neurons from hydrogen peroxide-induced neuronal death by inhibiting NLRP1 expression. In addition, HO-1 inhibited expression of activating transcription factor 4 (ATF4), which is a transcription factor regulating NLRP1 expression. CONCLUSIONS: HO-1 protects spinal cord neurons after SCI through inhibiting NLRP1 inflammasome formation.

High level of serum apolipoprotein A-I is a favorable prognostic factor for overall survival in esophageal squamous cell carcinoma.

BACKGROUND: Noninvasive prognostic tools for esophageal squamous cell carcinoma (ESCC) are urgently needed. Serum lipids and lipoproteins are used for the prognosis of certain diseases; however, the prognostic value of serum apolipoprotein A-I (ApoA-I) in ESCC has not been described. METHODS: Pre-treatment serum lipids and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) were analyzed retrospectively and compared between 210 patients with ESCC and 219 healthy controls. The prognostic significance of serum lipids and lipoproteins was determined by univariate and multivariate Cox hazard models in ESCC. RESULTS: Clinical characteristics (age, sex, pT status, pN status, pM status, pTNM status, histological differentiation or alcohol index) had no influence on baseline ApoA-I level. Serum ApoA-I, HDL-C, LDL-C, and TC levels were significantly lower and Apo-B was significantly higher in ESCC patients than in normal controls. On univariate analysis, ApoA-I, alcohol index, pT status, pN status and pTNM status were associated with significantly poor survival, and ApoA-I (p = 0.039), alcohol index (p = 0.037) and pTNM status (p = 0.000) were identified as prognostic factors associated with shorter survival in the multivariate analysis. CONCLUSIONS: Overall survival was shorter in ESCC patients with decreased pre-treatment ApoA-I levels. Our findings suggest that serum ApoA-I level should be evaluated as a predictor of survival in patients with ESCC.

Effects of Notch2 and Notch3 on Cell Proliferation and Apoptosis of Trophoblast Cell Lines.

AIMS: To investigate the effect of Notch2 and Notch3 on cell proliferation and apoptosis of two trophoblast cell lines, BeWo and JAR. METHODS: Notch2 and Notch3 expression in BeWo and JAR cells was upregulated or downregulated using lentivirus-mediated overexpression or RNA interference. The effect of Notch2 and Notch3 on cell proliferation was assessed by the CCK-8 assay. The effect of Notch2 and Notch3 on the apoptosis of BeWo and JAR cells was evaluated by flow cytometry using the Annexin V-PE Apoptosis kit. Lentivirus-based overexpression vectors were constructed by cloning the full-length coding sequences of human Notch2 and Notch3 C-terminally tagged with GFP or GFP alone (control) into a lentivirus-based expression vector. Lentivirus-based gene silencing vectors were prepared by cloning small interfering sequences targeting human Notch2 and Notch3 and scrambled control RNA sequence into a lentivirus-based gene knockdown vector. The effect of Notch2 and Notch3 on cell proliferation was assessed by the CCK-8 assay. And the effect of Notch2 and Notch3 on the apoptosis of BeWo and JAR cells was evaluated by flow cytometry using the Annexin V PE Apoptosis kit. RESULTS: We found that the downregulation of Notch2 and Notch3 gene expression in BeWo and JAR cells resulted in an increase in cell proliferation, while upregulation of Notch3 and Notch2 expression led to a decrease in cell proliferation. Moreover, the overexpression of Notch3 and Notch2 in BeWo and JAR cells reduced apoptosis in these trophoblast cell lines, whereas apoptosis was increased in the cells in which the expression of Notch3 and Notch2 was downregulated. CONCLUSIONS: Notch2 and Notch3 inhibited both cell proliferation and cell apoptosis in BeWo and JAR trophoblast cell lines.

Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis.

Apoptosis has been widely reported to be involved in the pathogenesis associated with spinal cord injury (SCI). Recently, autophagy has also been implicated in various neuronal damage models. However, the role of autophagy in SCI is still controversial and its interrelationship with apoptosis remains unclear. Here, we used an in vitro SCI model to observe a time-dependent induction of autophagy and apoptosis. Mechanical injury induced autophagy markers such as LC3 lipidation, LC3II/LC3I conversion, and Beclin-1 expression. Injured neurons showed decreased cell viability and increased apoptosis. To elucidate the effect of autophagy on apoptosis, the mechanically-injured neurons were treated with the mTOR inhibitor rapamycin and 3-methyl adenine (3-MA), which are known to regulate autophagy positively and negatively, respectively. Rapamycin-treated neurons showed the highest level of cell viability and lowest level of apoptosis among the injured neurons and those treated with 3-MA showed the reciprocal effect. Notably, rapamycin-treated neurons exhibited slightly reduced Bax expression and significantly increased Bcl-2 expression. Furthermore, by plasmid transfection, we showed that Beclin-1-overexpressing neuronal cells responded to mechanical injury with greater LC3II/LC3I conversion and cell viability, lower levels of apoptosis, higher Bcl-2 expression, and unaltered Bax expression as compared to vector control cells. Beclin-1-knockdown neurons showed almost the opposite effects. Taken together, our results suggest that autophagy may serve as a protection against apoptosis in mechanically-injured spinal cord neurons. Targeting mTOR and/or enhancing Beclin-1 expression might be alternative therapeutic strategies for SCI.

Identification of risk and prognostic factors for patients with clonorchiasis-associated intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma caused by clonorchiasis (CICC) has a poor prognosis, and there have been insufficient studies regarding risk and prognostic factors. We aimed to identify CICC-associated factors. METHODS: A retrospective analysis of 127 eligible patients with CICC was performed with 254 clonorchiasis cases used as matched controls to identify risk factors for CICC. The main outcomes analyzed included overall survival (OS) and disease-free survival (DFS). RESULTS: Out of 127 surgeries, R0 resection was performed in 61 patients, R1 in 32 patients, and R2 in 22 patients; nonresection surgery was performed in 12 patients. Median OS for the entire cohort was 29.5 months. Median OS and DFS for 61 patients with R0 resection were 52.4 months and 41.5 months, respectively. We found independent risk factors for CICC were duration of raw fish consumption of ≥28 years (p < 0.001) and hepatitis B virus infection (p = 0.040). R0 resection (p < 0.001), well or moderately differentiated tumor (p = 0.019), and stage I to II tumor (p < 0.001) predicted improved OS for CICC. Serum carcinoembryonic antigen level of ≤5 ng/ml (p = 0.029) and stage I to II tumor (p < 0.001) predicted improved DFS. CONCLUSIONS: Duration of raw fish consumption ≥28 years and hepatitis B virus infection were significant risk factors for CICC in patients with clonorchiasis. For patients with CICC, curative resection is an effective treatment. Higher tumor differentiation and earlier American Joint Committee on Cancer stage predicted good prognosis. Serum carcinoembryonic antigen level was found to predict the possibility of recurrence after curative resection.

Analysis of risk factors for pancreatic duct stones formation in patients with alcoholic chronic pancreatitis.

BACKGROUND: Alcoholic chronic pancreatitis (ACP) is the dominant cause of chronic pancreatitis (CP). As a main complication of CP, the formation of pancreatic duct stones (PDS) compromises pancreatic function and symptomatic patients are often subjected to aggressive treatments. The present study aimed to identify PDS risk factors in patients with ACP. METHODS: A retrospective analysis of 93 ACP patients was performed; patients were divided into two groups: ACP with PDS (n = 48) and ACP without PDS (n = 45). Fourteen potential factors were analyzed by univariate and multivariate analyses to identify independent risk factors of PDS formation in ACP patients. A comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS (n = 43) was also carried out. RESULTS: ACP accounted for 47.7% (93/195) of CP in this cohort. Among ACP patients, the morbidity of PDS was 51.6% (48/93). Significant risk factors of PDS formation for ACP patients included duration of drinking ≥24.7 years (OR, 9.036; 95% CI, 2.737-29.837; p < 0.001); daily alcohol consumption ≥147.0 g (OR, 3.147; 95% CI, 1.040-9.522; p = 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205-23.811; p = 0.001). Shorter periods between diagnosis and PDS formation (PDP) were observed in ACP patients than non-ACP patients. CONCLUSIONS: Alcohol consumption accelerates the progression of PDS formation in patients with CP.

Identification of prognostic factors and the impact of palliative resection on survival of patients with stage IV hepatolithiasis-associated intrahepatic cholangiocarcinoma.

BACKGROUND: Hepatolithiasis-associated intrahepatic cholangiocarcinoma (IHHCC) has a poor prognosis, because of lower curative resection rate when diagnosed in the advanced stage. There has been insufficient data regarding prognostic factors and the impact of palliative resection on its outcome. METHODS: A retrospective analysis of 78 eligible patients with stage IV IHHCC was performed. The potential prognostic factors were assessed by univariate and multivariate analyses. Patients were divided into groups A (margin positive) and B (nonresection) based on surgical methods. Demographic and operative data were compared. RESULTS: Of 78 surgeries, R1 was achieved in 11, R2 in 21 and nonresection in 46 patients. Median overall survival (OS) of the entire cohort was 10.5 months. Surgery (P < 0.01), tumor differentiation (P = 0.03), AJCC stage (P < 0.01), and serum CEA levels (P < 0.01) were independent prognostic factors. Significant differences were achieved in OS (P < 0.01), operation time (P < 0.01), estimated blood loss (P < 0.01), and postoperative complications (P = 0.02) between groups A and B. CONCLUSIONS: For patients with stage IV IHHCC, palliative resection is a rational and effective treatment. Normal serum CEA levels, higher tumor differentiation, and stage IVa predict good prognosis in stage IV IHHCC.

Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.

BACKGROUND/AIMS: To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. METHODS: SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. RESULTS: The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. CONCLUSIONS: The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI.

Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1.

In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32+ and Ctip2+ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.

FIM-A, a phosphorus-containing sirolimus, inhibits the angiogenesis and proliferation of osteosarcomas.

The mTOR pathway is a central control of cell growth, proliferation, metabolism, and survival, and is deregulated in most cancers. Cancer cells are addicted to increased activity of mTOR kinase-mediated signaling pathways, leading to numerous inhibitors of mTOR signaling in preclinic and clinical trials for cancer therapy. Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling, inhibits cancer cell growth in vitro. Here we report that FIM-A reduces the angiogenesis and proliferation of osteosarcoma both in vitro and in vivo. In cultured osteosarcoma cell lines, FIM-A inhibited cell proliferation and arrested cells in the G1 phase of the cell cycle, accompanied with reduction of VEGF and HIF-1alpha. With in vivo mouse osteosarcoma xenografts, FIM-A treatment resulted in the inhibition of mTORC1 signaling as demonstrated by the decreased phosphorylation of p70S6K1 and 4E-BP1. Consistent with this finding, FIM-A significantly decreased the average tumor volume, nuclei staining of PCNA, and the number of intratumoral microvessels. Our data demonstrated that targeting mTORC1 by FIM-A inhibited the growth of osteosarcoma in vitro and in vivo, providing the basis for further development of FIM-A as a therapy for osteosarcoma patients.