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This study was conducted to evaluate the predictive efficacy of tumor mutation burden (TMB) in patients with non-small-cell lung cancer (NSCLC) receiving PD-1 antibodies. Embase, PubMed, Ovid Medline, and the Cochrane Library were systematically searched until May 24, 2020. The keywords included "PD-1," "TMB," and "NSCLC." Overall survival (OS) and progression-free survival (PFS) were summarized and combined using the hazard ratio (HR) and 95% confidence interval. Twenty-one studies with 9883 patients were included in the meta-analysis. The overall relapse rate ranged from 39.3% to 64.3% in the higher TMB group as compared with 0% to 40% in the lower TMB group. The median OS ranged from 2.9 to 23 mo in the higher TMB group as compared with 4.3 to 16.2 mo in the lower TMB group. Patients with a higher TMB had a better OS as compared with patients with a lower TMB (HR = 0.61, P < 0.001). Similarly, a higher TMB was also a good predictor of PFS in patients treated with PD1/PDL1 antibodies (HR = 0.55, P < 0.001). Our results suggest that among NSCLC patients receiving PD1/PDL1 antibodies, patients with higher TMB could have a better survival outcome.

Background Motoric cognitive risk syndrome (MCR) is a newly proposed predementia syndrome incorporating subjective cognitive complaints and slow gait. Previous studies have reported that subjective cognitive complaints and slow gait are associated with frailty in cognitively unimpaired older adults, but little is known about the link between MCR and frailty in older adults. Therefore, the aim of the study was to explore the associations of MCR and its components with frailty in older Chinese adults. Methods In an observational cross-sectional study, a total of 429 older adults aged 60 years and older were admitted to the geriatric department. According to MCR criteria, all participants were classified into 4 groups: 1) the MCR group; 2) the subjective cognitive complaints only group; 3) the slow gait only group; and 4) the healthy control group. Physical frailty was assessed by the Clinical Frailty Scale (CFS). Multivariate logistic regression analysis was used to examine the association between MCR and frailty in older adults. Results The prevalence rates of subjective cognitive complaints, slow gait and MCR were 15.9, 10.0 and 4.0%, respectively. After adjusting for confounding variables, the logistic regression analysis showed that slow gait (odds ratio [OR]: 3.40, 95% confidence interval [CI]: 1.40–8.23, P = 0.007) and MCR (OR: 5.53, 95% CI: 1.46–20.89, P = 0.012) were independently associated with frailty, but subjective cognitive complaints were not. Conclusions MCR and slow gait were significantly associated with frailty in older Chinese adults. Further studies should prospectively determine the causal relationship between MCR and frailty.

Purpose The study aimed to investigate the association between body composition and frailty in elder inpatients. Patients and Methods This is a cross-sectional study including 656 elder inpatients (275 females and 381 males) aged ≥65 years, from department of geriatrics of Zhejiang Hospital between January 2018 and March 2019. Sociodemographic, health-related data and anthropometric measurements were evaluated. Body composition was assessed by bioimpedance analysis (BIA), mainly including skeletal muscle mass, body fat mass, total body water, fat-free mass,percent body fat, basal metabolic rate. Frailty was assessed by Clinical Frailty Scale (CFS). Univariate logistic regression was used to analyze the association between body composition and frailty. Results Frailty was present in 43.9% of the participants. Frail inpatients showed higher waist circumference, body fat mass and percent body fat, non-frail inpatients showed greater upper arm circumference, calf circumference, skeletal muscle mass, total body water, fat-free mass and basal metabolic rate. Subjects with underweight (body mass index (BMI)

Background. Endocrinopathies are common in patients withβ-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism inβ-thalassemia major based on a meta-analysis.Methods. PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) inβ-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients withβ-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted.Results. A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM inβ-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders inβ-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias.Conclusion. High prevalence of endocrine disorders involving abnormal glucose metabolism was detected inβ-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide; however, accurate prognostic tools are still lacking. We aimed to identify immunohistochemistry (IHC)-based signature as a prognostic classifier to predict recurrence and survival in patients with HCC at Barcelona Clinic Liver Cancer (BCLC) early- and immediate-stage. In total, 567 patients who underwent curative liver resection at two independent centers were enrolled. The least absolute shrinkage and selection operator regression model was used to identify significant IHC features, and penalized Cox regression was used to further narrow down the features in the training cohort (n = 201). The candidate IHC features were validated in internal (n = 101) and external validation cohorts (n = 265). Three IHC features, hepatocyte paraffin antigen 1, CD34, and Ki-67, were identified as candidate predictors for recurrence-free survival (RFS), and were used to categorize patients into low- and high-risk recurrence groups in the training cohort (P < 0.001). The discriminative performance of the 3-IHC_based classifier was validated using internal and external cohorts (P < 0.001). Furthermore, we developed a 3-IHC_based nomogram integrating the BCLC stage, microvascular invasion, and 3-IHC_based classifier to predict 2- and 5-year RFS in the training cohort; this nomogram exhibited acceptable area under the curve values for the training, internal validation, and external validation cohorts (2-year: 0.817, 0.787, and 0.810; 5-year: 0.726, 0.662, and 0.715; respectively). The newly developed 3-IHC_based classifier can effectively predict recurrence and survival in patients with early- and intermediate-stage HCC after curative liver resection.

Background: Tumor-to-tumor metastasis is an extremely rare but interesting phenomenon. Prostatic cancer metastasizing to malignant solitary fibrous tumor (SFT) of the lung has not been previously reported.Case Presentation: In this report, we describe the case of a 60-year-old man presenting a large solitary neoplasm in the left lung on computed tomography. Pathology after left lung wedge resection indicated two different cancerous cell components: SFT cells with malignant potential and prostatic cancer cells. The heterogeneous cells of prostatic origin were confirmed by using evidence from fine needle aspiration and pathology after radical prostatectomy.Conclusions: We report the first tumor-to-tumor metastasis of prostatic cancer to lung malignant SFT.

Background: Intrinsic capacity (IC) is a novel view focusing on healthy aging. The effect of IC on adverse outcomes in older hospitalized Chinese adults is rarely studied. Objectives: This study focused on investigating the impact of IC domains on the adverse health outcomes including new activities of daily living (ADL) dependency, new instrumental activities of daily living (IADL) dependency, and mortality over a 1-year follow-up. Methods: In a retrospective observational population-based study, a total of 329 older hospitalized patients from Zhejiang Hospital in China were enrolled and completed 1-year follow-up. The 5 domains of IC including cognition, locomotion, sensory, vitality, and psychological capacity were assessed at admission. The IC composite score was calculated based on these domains, and the higher IC composite score indicated the greater amount of functional capacities reserved. Multivariate logistic regression models were used to explore the association between IC at baseline and 1-year adverse outcomes. Results: During the 1-year follow-up, 69 patients (22.5%) experienced new ADL dependency, 103 patients (33.6%) suffered from new IADL dependency, and 22 patients (6.7%) died. After adjusting for age, sex, education level, comorbidities, and polypharmacy, low Mini-Mental State Examination (MMSE) scores at admission predicted 1-year new ADL dependency (odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.12–4.78) and new IADL dependency (OR = 2.15, 95% CI: 1.14–4.04) among older hospitalized patients, but no significance was obtained between IC domains and mortality. Higher IC composite score at admission was associated with decreased risks of 1-year new ADL dependency (OR = 0.53, 95% CI: 0.40–0.70) and new IADL dependency (OR = 0.76, 95% CI: 0.61–0.95), and 1-year mortality (OR = 0.48, 95% CI: 0.31–0.74) after adjustment for the possible confounders. Conclusions: Loss of ICs at admission predicted adverse health outcomes including new ADL and IADL dependency and mortality 1 year after discharge among older hospitalized patients.

Purpose Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a recently discovered protein that is considered important in causing mutations in tumor cell genome bases. Whether APOBEC3B is expressed in nasopharyngeal carcinoma (NPC) still remains unknown. Studies have shown that programmed-cell-death receptor-1 ligand (PD-L1) is highly expressed in NPC, but its clinical significance has not been fully elucidated. We aimed to evaluate APOBEC3B and PD-L1 protein expression in NPC and also investigate their prognostic significance. Materials and methods One hundred and three patients with NPC were retrospectively collected in this study, and were followed-up for 5 years. The expression of APOBEC3B and PD-L1/PD-1 in NPC was detected by immunohistochemical staining. Results High expression of APOBEC3B was observed in 42.7% of NPC patients. The high expression rate of APOBEC3B was 31.5% in patients without recurrence or metastasis within 5 years, and 55.1% in those patients with recurrence or metastasis, and the difference was statistically significant (P=0.016). There was no significant difference in APOBEC3B expression among patients with different sex, age group, and clinical stage (P>0.05). The positive expression rate of PD-L1 was 55.3% in all patients with NPC. There was no significant difference in PD-L1 expression among patients with different sex, age group, clinical stage, and tumor recurrence or metastasis condition (P> 0.05). There was no significant correlation between the expression of APOBEC3B and PD-L1 in NPC patients. The positive expression rate of PD-1 was 1.9% (2/103) in patients with NPC. Conclusions APOBEC3B showed association with aggressive behavior and poor outcome in NPC, and is also considered as a potential marker for predicting NPC recurrence or metastasis. PD-L1 is not associated with the aggressive behavior and poor outcome in NPC.

Objectives To evaluate pretreatment tumor thickness in predicting pathologic complete response (pCR) of stage II/III rectal adenocarcinoma to neoadjuvant chemoradiation (chemoradiotherapy [CRT]). Methods We retrospectively analyzed 185 patients who were diagnosed with stage II or III rectal adenocarcinoma from January 2011 to July 2013 and treated with neoadjuvant intensity-modulated radiation therapy (45 Gy in 1.8-Gy fractions to pelvis and 50 Gy in 2-Gy fractions to rectal tumor as an integrated boost) or 3 dimensionally conformal radiation therapy (45 Gy in 1.8-Gy fractions to pelvis followed by an additional 5.4-Gy to rectal tumor) concurrently with two 3-week cycles of chemotherapy (oxaliplatin 130 mg/m on day 1 and capecitabine 825 mg/m, twice per day from day 1 to 14, cycle 2 starts on week 4). One week after CRT, 36% patients received 1 more cycle of the above chemotherapy and 55% received 1 to 2 cycles of FOLFOX6. Tumor response was categorized as pCR and non-pCR. Tumor thickness measured on magnetic resonance imaging was collected. A multivariate logistic regression model was used to evaluate the association of potential predictors and pCR. Results Thirty-eight patients (20.5%) reached pCR. Multivariate analysis found the pretreatment tumor thickness to be associated with higher probability of pCR after adjusting for radiation therapy-surgery interval time and pretreatment carcino-embryonic antigen level. The pretreatment carcino-embryonic antigen level was associated with pCR in the univariate analysis but lost the association in the multivatiate model. The pretreatment T or N stage, tumor volume, distance from tumor to anal verge, craniocaudal length of tumor, radiation therapy technique, and patient age and sex were not associated with pCR. Conclusions We concluded that pretreatment tumor thickness is an independent predictor for pCR of stage II/III rectal adenocarcinoma to the neoadjuvant CRT.

Objective: To investigate the proportion of HER2 gene amplifications and the association between the HER2-IHC-staining pattern and gene status in IHC-2+ breast cancers according to 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Methods: We retrospectively analyzed and re-evaluated the IHC-staining pattern of 2538 IHC-2+ surgical specimens of breast cancer from November 2014 to October 2015 in 12 institutions. All cases used for building a prediction model of HER2 gene amplification according to the IHC-staining pattern and were randomly divided into a training set (n = 1914) or validation set (n = 624). Results: The overall HER2 fluorescence in situ hybridization (FISH) amplification, non-amplification and equivocation rates in HER2 IHC-2+ cases were 17.8%, 76.2% and 6.0%, respectively. In the training set, cases that had ≤ 10% of cells with intense, complete and circumferential membrane staining or had > 85% of cells with complete membrane staining of any staining intensity tended to be HER2 gene amplified (77.0% and 60.5%, respectively). And cases with weak and incomplete membrane staining had the lowest amplification rate of 6.1%. The prediction model was constructed based on IHC-staining pattern in the training set and validated using a validation set. The positive and negative prediction values were 51.6% and 79.2%, respectively, in the validation set. Moreover, the HER2 copy number per cell was much higher in cases with amplification-associated staining patterns (7.84 and 8.75) than in cases with non-amplification-associated staining patterns (2.97 to 4.41, P < 0.05). Conclusions: In HER2 IHC-2+ breast cancers, the staining pattern is associated with the HER2 gene status. This finding is compatible with recommendations of 2013 ASCO/CAP guidelines.

This study aimed to investigate the value of 99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([99mTc]3PRGD2) imaging in diagnosis and staging of breast cancer compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) imaging, and to explore the expression of integrin αvβ3 in tumor vascular endothelial cells. Forty-two women with suspected breast cancer underwent both [99mTc]3PRGD2 imaging and [18F]FDG imaging. Visual analysis was used to assess primary breast lesion, axillary lymph node, and distant metastasis. The tumor-blood (T/B) ratios from [99mTc]3PRGD2 imaging and the maximum standardized uptake value (SUVmax) from [18F]FDG imaging were analyzed for breast lesions. Integrin αvβ3 was analyzed through immunohistochemistry. Forty-five breast lesions were found (malignant, n = 38; benign, n = 7). The sensitivity, specificity, and accuracy of [99mTc]3PRGD2 and [18F]FDG imaging in visual analysis for the breast lesion were 97.4, 87.5, and 95.6 % and 97.4, 71.4, and 93.3 %, respectively (P > 0.05). For semi-quantitative analysis, no significant difference of the area under the curves (AUC) was found in the imaging using the two radiopharmaceuticals (0.880 and 0.955; Z = 0.88, P > 0.05). The sensitivity, specificity, and accuracy for axillary lymph node metastasis with [99mTc]3PRGD2 and [18F]FDG were 78.05, 99.36, and 94.92 % and 85.37, 98.72, and 95.64 %, respectively (P > 0.05). Nine patients with distant metastases were all detected with the two radiopharmaceuticals. The expression of integrin αvβ3 was correlated with [99mTc]3PRGD2 uptake (r = 0.582, P = 0.001), which were significantly higher in the HER2-positive and stage III–IV patients (P

In this study, we compared the systemic stress response induced by microwave ablation with that induced by conventional open surgery for treatment of benign thyroid nodules.A total of 108 patients with benign thyroid nodules were randomly assigned to receive ultrasound-guided thyroid microwave ablation (microwave group, n = 57) and conventional open thyroid surgery (open group, n = 51). Body temperature, white blood cell (WBC) counts, visual analogue scale (VAS) scores for pain, and serum levels of high sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and cortisol were measured at 24 h before operation and at 8 h, 24 h and 48 h after operation.No significant between-group differences were observed with respect to preoperative body temperature, VAS scores, WBC counts, serum hs-CRP, IL-6 and cortisol levels. Patients in the open group exhibited higher body temperature at 24 h after operation and higher WBC counts at both 24 h and 48 h after operation, as compared to those in the microwave group. As compared with microwave ablation, open surgery was associated with significantly higher VAS scores, and significantly higher serum levels of hs-CRP, IL-6 and cortisol at all postoperative time-points (8 h, 24 h and 48 h).Microwave ablation induces a lower systemic stress response than open surgery for treatment of benign thyroid nodules.

Purpose: To investigate the clinicopathological features of patients with breast microinvasive carcinoma (MI). Methods: The clinical data of 121 cases with breast MI were retrospectively collected. The whole tumor in each case was stained with hematoxylin and eosin (H&E) for pathological evaluation. The relationships among size of tumor, histological grade, tumor-infiltrating lymphocytes (TILs), the number of MIs, type of MI, and lymph node metastasis were analyzed. Results: It was revealed that 86% of the cases had high-grade ductal carcinoma in situ (DCIS) and 63.6% had multiple MIs. The larger size of the tumors, the higher the grade of DCIS, the more the number of MIs; 3.3% of cases had rich TILs (lymphocyte/stroma > 30%) in the DCIS, and 26.5% had rich TILs in MIs. The type A of MIs is characterized by single cells and small clusters of solid cells. Tumor cells in type B of MIs can form glandular ducts. Formal grading of microinvasive is challenging/impossible due to its limited size precluding a representative mitotic count. But nuclear grade and tubule (differentiation) grades can be reported. In addition, 72.7% of cases had type A of MIs and 27.3% of cases had type B of MIs. Type B was found to be highly accompanied by moderate-grade DCIS. Only 6.6% of patients with MI had lymph node metastasis, which was mainly related to MIs with less TILs. Conclusion: Breast MI is easy to occur in high-grade DCIS, and multiple infiltration foci may be observed in case with tumor size of higher than 3.5 cm. Microinvasive carcinoma with poor TILs maybe a risk factor for lymph node metastasis in patient with DCIS-Mi.

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is known as a source of mutations in multiple cancers. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of heterogeneous tumors. However, the expression and significance of APOBEC3B in GEP-NENs remains unclear.A total of 158 cases of GEP-NENs, including 78 cases of biopsy or endoscopic submucosal dissection resection specimens and 83 cases of surgical resection specimens were collected in this study. The cases were grouped according to tumor classification grade, including 42 cases of neuroendocrine tumors G1 (NET G1), 36 cases of NET G2, 36 cases of NET G3, 44 cases of neuroendocrine carcinoma (NEC). All of the 158 tumors were immunohistochemically studied using a polyclonal antibody against APOBEC3B. We evaluated APOBEC3B expression in GEP-NENs and investigated the relationships among the immunoreactivity of APOBEC3B, clinical and pathologic features, such as age, sex, tumor site, Ki67 cell proliferation index, and lymph metastasis.A total of 33 cases (78.6%) of NET G1 showed high expression of APOBEC3B. A total of 28 cases (77.8%) of NET G2 demonstrated high expression of APOBEC3B. In NET G3 and NEC cases, the positive rates were 52.8% and 2.3%, respectively. The expression of APOBEC3B in NETs was significantly higher than that in NECs, NET G1 and NET G2 were higher than NET G3, and the difference was statistically significant. APOBEC3B high expression cases have lower lymph node metastasis rate, lower Ki67 cell proliferation index.In this study, APOBEC3B is highly expressed in GEP-NETs and is a predictor of lymph node metastasis in NET G3 and NEC cases. These findings might provide new insights into the biological mechanisms of GEP-NENs tumorigenesis and progression.

Assessment of tumor invasion depth prior to making therapeutic decisions in colorectal carcinoma is crucial for both the patient and the physician. In this paper, multiphoton microscopy (MPM) was used to simultaneously label freely image loose areolar connective tissue in the submucosa and intramuscular septa in the muscularis propria to perform assessment of colorectal carcinoma invasion depth. The results indicated that MPM can accurately exhibit whether colorectal carcinoma invades into the submucosa or the muscularis propria. Collagen content alteration and the presence of dirty necrosis can be extracted to serve as quantitatively intrinsic biomarkers for reflecting collagen degradation, the occurrence of desmoplastic reaction, and breakdown of cancer cells, which are tightly related to the prognosis of colorectal carcinoma. With the development and clinical applications of the multiphoton endoscope, in vivo histological-like diagnosis of tumor invasion depth may become its main application in the field of colorectal carcinoma and lead to faster and improved therapeutic decision making in the clinics.

This study was designed to analyze the clinical characteristics and prognostic value of c-MYC and BCL-2 proteins expression in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). 82 patients newly diagnosed with PCNS-DLBCL, from January 2008 to November 2018, were enrolled in this study. Clinical characteristics, immunohistochemical features, laboratory examinations, and treatment outcome were analyzed among these patients. Among these 82 cases, 45 were males (54.9%) and 37 were females (45.1%). Age ranged from 16 to 78 years old, and 29 patients (35.4%) were elder than 60 years old, with median age at 57 years old. According to Hans classification, 25 were accounted for origin of germinal center B-cell (GCB) subtype (30.5%) and 49 were accounted for non-GCB subtype (59.8%), respectively. Eight patients were unclassified due to lack of detailed pathological results. The median survival of these 82 patients was 30 months, and 1-year, 3-year, and 5-year overall survival (OS) rate was 59.7%, 44.6%, and 34.1%, respectively. Patients treated with sequential HD-MTX based chemotherapies showed a superior prognosis than those without. In combination with rituximab, the outcome was further improved. The median OS was 55 months in HD-MTX + R group, 27 months in HD-MTX group, and 9 months in other groups, respectively. Univariate analysis identified age ≥60, ECOG score ≥ 2 points, and overexpression of BCL-2 protein (≥85%) were adverse prognostic factors for OS. Co-expression of c-MYC (≥40%) and BCL-2 (≥50%) proteins was associated with poor ECOG score, high Ki-67 expression, and trended towards an inferior outcome. Gender, lesion location, number of lesions, lactic dehydrogenase (LDH), cell of origin, BCL-6 protein expression, expression of c-MYC protein alone and Ki-67 ≥85% had no significant impact on OS. In patients with PCNS-DLBCL, age ≥60 years old, ECOG score ≥2 points, and overexpression of BCL-2 protein (≥85%) were associated with a poor survival. HD-MTX based chemotherapies in combination with rituximab could improve the prognosis.

Background The optimal duration of Imatinib adjuvant treatment for patients with high-risk gastrointestinal stromal tumors (GISTs) is uncertain. Patients and Methods A total of 90 patients with high-risk GISTs after curative resection were recruited into this non-randomized case–control study, including 35 having Imatinib adjuvant therapy and 55 having follow-up alone. The recurrence-free survival (RFS) was compared. Results After a median follow-up of 44.0 months, a significantly reduced recurrence rate was observed in the treatment group than the control group (17.1% vs. 78.2%, P = 0.000). One-year, 2-year, and 3-year RFS rates were 100% vs. 70.9%, 88.0% vs. 37.8%, and 88.0% vs. 27.5%, respectively; with a significant advantage for Imatinib adjuvant therapy versus the surgery only (P = 0.000, HR 0.122, 95% CI 0.041–0.363). Continuation Imatinib treatment further improved RFS by comparison with the interruption treatment (both 2-year and 3-year RFS were 95.8% vs. 63.6%, P = 0.011, HR 0.103, 95% CI 0.012–0.883). There were no serious adverse events in the adjuvant therapy group. Conclusions Imatinib Adjuvant therapy could significantly prolong the RFS of patients with high-risk GISTs. Extended Imatinib adjuvant treatment strategy may further reduce the risk of relapse with a low drug resistance rate and toxicity profile. J. Surg. Oncol. 2011; 104:760–764. © 2011 Wiley Periodicals, Inc.

Multiphoton microscopy based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) was firstly employed to investigate pathological process from the unaffected skin to the erythematous phase and to finally affected skin of Jadassohn-Pellizzari anetoderma. Our study showed that the normal elastic fibers in unaffected skin were almost completely absent in erthematous skin tissue, then replaced by a lot of elastic fibers with granular morphology in affected skin. The obvious change of collagen fibers and occurrence of inflammatory cell infiltration in erthematous tissue suggested that variation of these two components were also main pathogenesis of anetoderma except for deficiency of elastic fibers. Our results give a sight to noninvasively study the pathological process of skin disease and the other disease with tight relation to variation of collagen and elastic fibers in skin dermis and cell in skin epidermis.

Integrating the solar utilization system with the coal- fired power plant into the solar supported coal-fired power generation (SSCPG) system shows an effective way for the large- scale utilization of solar energy and energy conservation in coal- fired power units currently in China. Two SSCPG systems integrating solar utilization system with C50-8.83/0.294 heat and electricity cogeneration unit are taken as examples to analyze its economy. Firstly, thermal performances of these two SSCPG systems are given by using solar heat electricity efficiency, solar heat input fraction, solar electricity generation fraction and so on as thermal economy evaluating indicators. The influence of location, operation mode on their thermal performance is also discussed. Then unit electricity generation cost of the SSCPG system is calculated, in which investment cost is involved. The results show that, on the condition assumed in this paper, the unit electricity generation cost of the SSCPG system of reducing 1# bled steam individually is 0.0386$/kW�‹ h, a little higher than that of the coal-fired only system, 0.0356$/kW�‹ h. But the unit electricity generation cost of solar part of it is 0.082$/kW�‹ h, lower than that of solar only electricity generation system, 0.14$/kW�‹ h. Finally, sensitivity analysis on the unit electricity generation cost is conducted. And the conclusion is that when collector price drops to 48$/m 2 and coal price increases to 368$/t meanwhile, the unit electricity generation cost of the SSCPG system of reducing 1# bled steam individually will be equal to that of the coal-fired only system as the discount rate is 12%.

The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.

The monitoring and evaluation of colorectal adenoma–carcinoma sequence during endoscopy are important for endoscopic resection of precursor lesions to disrupt the adenoma–carcinoma sequence and halt progression to invasive neoplastic disease. In this study, multiphoton microscopy (MPM) was used to identify different stages during the development of colorectal adenocarcinoma including adenoma with low-grade and high-grade dysplasia, and adenocarcinoma invading the submucosa. It was found that by combining two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging, MPM can reveal the morphological changes of the epithelial cells and glands, identify the invasive position and depth of atypical glands and quantitatively describe the change of the cellular nucleus and the nuclear-to-cytoplasmic ratio during the stepwise progression of colorectal adenocarcinoma. These are important pathological findings for pathologists when diagnosing colorectal lesions. With the advancement of a compact and flexible multiphoton endoscope for in vivo imaging and clinical applications, MPM has the potential to provide immediate histological diagnosis for the monitoring and evaluation of the colorectal adenoma–carcinoma sequence during endoscopy.

Discoid lupus erythematosus (DLE) is a chronic dermatological disease which lacks valid methods for early diagnosis and therapeutic monitoring. Considering the collagen and elastin disorder due to mucin deposition of DLE, multiphoton microscopy (MPM) imaging techniques were employed to obtain high-resolution collagen and elastin images from the dermis. The content and distribution of collagen and elastin were quantified to characterize the dermal pathological status of skin lesions with DLE in comparison with normal skin. Our results showed a significant difference between skin lesions with DLE and normal skin in terms of the morphological structure of collagen and elastin in the dermis, demonstrating the possibility of MPM for noninvasively tracking the pathological process of DLE even in its early stages and evaluating the therapeutic efficacy at the molecular level.