Impact of Diabetic Nephropathy on Pulmonary Function and Clinical Outcomes.

Objective: The main objective is to study the effect of diabetic nephropathy on pulmonary function and clinical outcomes. Methods: The method is to retrospectively analyze patients with diabetic nephropathy (DN) in our hospital from April 2018 to March 2022 as study subjects. The differences in baseline data, serum indicators, renal function indicators, and pulmonary function of patients at different clinical stages were analyzed and then explored. Finally, logistic regression was used to analyze the risk factors affecting patients' clinical outcomes and to evaluate the diagnostic effects. Results: Baseline information (age, disease duration, BMI, and systolic and diastolic blood pressure), serum indicators (HbA1c, FBG, 2hPG, TG, TC, and LDLC), renal function indicators (CysC, BUN, and Scr), and pulmonary function (TLC, VC, FEV1, FEV1/FVC, MVV, MEF25, MEF50 MEF75, DLCO, and DLCO/VA) were significantly different (P < 0.01); multiple logistic regression analysis showed that SBP, HbA1c, FBG, 2hPG, BUN, Scr, TLC, VC, FEV1/FVC, MVV, DLCO, and DLCO/VA were all key factors in the development of clinical outcomes in DN (P < 0.05). ROC analysis showed that all of these important factors had an AUC greater than 0.75 for the diagnosis of DN with high sensitivity and specificity. Conclusion: Serum and renal function indices of DN patients gradually increased with stage, accompanied by a decrease in pulmonary ventilation, and diffusion function; SBP, HbA1c, FBG, 2hPG, BUN, Scr, TLC, VC, FEV1/FVC, MVV, DLCO, and DLCO/VA were all key factors affecting the clinical outcome of DN; controlling blood glucose, lipids, improving pulmonary ventilation, and diffusion function can better prevent the occurrence and worsening of DN.

Invasive Micropapillary Carcinoma with CEP17 Monosomy of the Bilateral Breast: A Rare Case Report and Review of the Literature.

Invasive micropapillary carcinoma (IMPC) is a novel type of breast cancer which is potentially very aggressive and may show early lymphatic infiltration. Monosomy of chromosome 17 (m17) is rare in breast cancer, and according to the 2018 guidelines of the American Society of Clinical Oncology/College of American Pathologists, the decision to administer trastuzumab treatment should be made based on positive human epidermal growth factor receptor 2 results by immunohistochemistry. Here, we report a rare case of bilateral local advanced IMPC involving m17. A 33-year-old woman found a mass measuring 30 mm on the left breast that increased to 100 mm over 3 months. A diagnosis of IMPC was made based on the findings of core needle biopsies of bilateral breast masses and left axillary lymph node, and m17 was detected by fluorescence in situ hybridization (FISH). The patient underwent 6 cycles of neoadjuvant chemotherapy (docetaxel, epirubicin, and cyclophosphamide) and left-side modified radical mastectomy, left axillary lymph node dissection, right breast-conserving surgery, and right sentinel lymph node biopsy. Postoperative pathologic analysis of both breasts revealed IMPC, and m17 was confirmed by FISH. The patient received radiotherapy and endocrine therapy but rejected trastuzumab treatment. The patient was still alive at the 30-month follow-up, without recurrence or metastasis. Our findings suggest that loss of chromosome 17 may influence prognosis or therapeutic response, which needs to be further confirmed.

Comparison of efficacy of stereotactic body radiotherapy and thoracoscopic surgery in the treatment of early-stage non-small cell lung cancer.

PURPOSE: To observe and compare the efficacy and safety between stereotactic body radiotherapy and thoracoscopic surgery in the treatment of early-stage non-small cell lung cancer (NSCLC). METHODS: The clinical data of 106 early-stage NSCLC patients admitted to the Thoracic Surgery Department of the hospital from February 2014 to February 2016 were retrospectively analyzed. Among these patients, 53 received stereotactic body radiotherapy (SBRT group), and 53 underwent video-assisted thoracoscopic surgery (VATS group). The clinical data of all patients were collected. The short-term response rate, Karnofsky performance status (KPS) score, changes in serum tumor marker levels before and after surgery and adverse reactions were compared between the two groups. Besides, all patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded. RESULTS: The levels of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and neurone specific enolase (NSE) were decreased in both groups after treatment, and the differences were not statistically significant between the two groups. The patients tolerated well with SBRT, without evident myelosuppression or adverse hematological effects. In SBRT group, there were 7 cases of radioactive skin reaction, 2 cases of grade I radiation esophagitis and 4 cases of radiation pneumonitis (including 3 cases of grade I radiation pneumonitis and 1 case of grade II radiation pneumonitis). In VATS group, there were 3 cases of incision infection, 2 cases of pulmonary infection, 5 cases of pulmonary atelectasis, 1 case of pulmonary leakage and 1 case of deep vein thrombosis of lower extremity. The 3- year OS and PFS were 79.2% (42/53) and 67.9% (36/53) and 83.0% (44/53) and 77.4% (41/53) in SBRT group and VATS group, respectively. Kaplan-Meier survival showed no statistically significant differences in the OS and PFS between the two groups (log-rank). CONCLUSION: SBRT achieves better RR and DCR, similar OS and PFS to those of typical thoracoscopic surgery, and good patient tolerance in the treatment of early- stage NSCLC, which is a safe and effective treatment means.

Successful surgical treatment of Cronkhite-Canada Syndrome with bilateral flail chest: a case report.

BACKGROUND: Development of multiple rib fractures leading to bilateral flail chest in Cronkhite-Canada Syndrome (CCS) has not been reported. CASE PRESENTATION: A 59-year-old man presented with complaints of fatigue, chest pain, respiratory distress and orthopnea requiring ventilatory support to maintain oxygenation. CCS with bilateral anterior and posterior flail chest due to multiple rib fractures (2nd-10th on the right side and 2nd-11th on the left side). He underwent open reduction and anterior and posterior internal fixation using a titanium alloy fixator and a nickel-titanium memory alloy embracing fixator for chest wall reconstruction. He recovered gradually from the ventilator and showed improvement in his symptoms. He gained about 20 kg of weight in the follow up period (6 months after discharge from the hospital). CONCLUSION: CCS is a rare, complex disease that increases the risk of developing multiple rib fractures, which can be successfully treated with open reduction and internal fixation.

Uncoupling protein 2 is upregulated in melanoma cells and contributes to the activation of Akt/mTOR and ERK signaling.

The aim of the present study was to characterize the expression of uncoupling protein 2 (UCP2) in melanoma and to study the potential mechanisms underlying the involvement of UCP2 in melanomagenesis using human melanoma cell lines. The expression of UCP2 was evaluated in specimens from normal control subjects, patients with compound nevus, and patients with cutaneous and mucosal melanoma. Stable knockdown of UCP2 was achieved in human melanoma cell lines, which were used to examine whether UCP2 knockdown affects the mitochondrial membrane potential and intracellular levels of ATP, reactive oxygen species and lactate. Cell proliferation, invasion, spheroid formation and cisplatin sensitivity were also evaluated in the UCP2 knockdown cells. Finally, the effects of UCP2 knockdown on the Akt/mammalian target of rapamycin (mTOR) and extracellular signal­regulated kinase (ERK) pathways, which are important oncogenic pathways during melanomagenesis, were evaluated. Relatively high expression of UCP2 was detected in human melanoma specimens, which was correlated with Clark level and Breslow thickness. Knockdown of UCP2 suppressed cell proliferation, invasion and spheroid formation, and increased the sensitivity of melanoma cells to cisplatin. Furthermore, the UCP2 knockdown cells exhibited inhibition of Akt/mTOR signaling and ERK activation. Therefore, human melanoma tissues exhibit relatively high UCP2 expression, which may be implicated in the mechanisms underlying tumor progression. The potential role of UCP2 in melanomagenesis may involve enhancing the Akt/mTOR and mitogen­activated protein kinase/ERK pathways.

Animal Study to Evaluate the Effect of Carbon Dioxide Insufflation on Recurrent Laryngeal Nerve Function in Transoral Endoscopic Thyroidectomy.

Data with regard to potential recurrent laryngeal nerve (RLN) compromise caused by intra-neck CO2 insufflation during transoral endoscopic thyroidectomy vestibular approach (TOETVA) are missing. RLN electromyographic (EMG) profiles, metabolic and hemodynamic parameters (oxygen saturation, heart rate, blood pressure, experimental time, CO2 partial pressure, pH, O2 partial pressure), central venous pressure (CVP), airpocket temperature and pressure were recorded in a TOETVA animal model. Twelve pigs were randomly divided into different groups according to increasing CO2 insufflation pressures. Nerves segments were then collected for histopathology. Significant variation of metabolic and hemodynamic parameters were registered when CO2 insufflation pressures increased x3 and x5 the baseline parameters. Combined EMG amplitude drop and latency increase also were documented. There was no significant change in the intraluminal temperature. RLNs structure were preserved with normal axons, no fibrosis, and no vacuolization and without loss of myelinated fibers during the experiment. RLN EMG profiles (but not histology) were altered when CO2 insufflation pressures increased.

Internal Carotid Artery Embolism After Autologous Fat Injection for Temporal Augmentation.

BACKGROUND: There have been several reports of patients experiencing cerebral embolisms following the injection of autologous fat into the face during cosmetic surgery. These embolisms likely resulted from unintentional introduction of fat particles into facial arteries, which then reached the cerebral arteries by retrograde motion. CASE PRESENTATION: We describe here a patient who developed an internal carotid artery (ICA) embolism after autologous fat injection for temporal augmentation. To our knowledge, this is the first report of a pathologically proven ICA embolism after fat injection into the face. CONCLUSIONS: Our results suggest that the fat particles reached the cerebral arteries via a previously unknown pathway. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Postmortem Study Exploring Distribution and Patterns of Intracranial Artery Calcification.

Background and Purpose- Intracranial artery calcification detected by computed tomography is associated with ischemic stroke as an indicator of intracranial atherosclerosis. However, little is known about its histopathology. This study aimed to explore the intracranial calcification patterns and their associations with atherosclerotic plaques. Methods- We recruited 32 adult autopsy cases to assess the calcification patterns and distributions in the middle cerebral artery, vertebral artery, and basilar artery. The relationships of calcification patterns with plaque phenotype and luminal stenosis were evaluated. The calcification patterns on computed tomography were correlated with that on histology. Results- Visible calcifications were detected within 37 (39%) segments, including 25 segments with intimal calcification, 6 segments with internal elastic lamina calcification, 3 segments with adventitial calcification, and 3 segments with concurrent calcification. Calcification occurred more often in the vertebral artery (51%), followed by the middle cerebral artery (35%) and basilar artery (14%; P<0.01 for vertebral artery versus basilar artery). Internal elastic lamina calcification was predominantly detected in the vertebral artery (7/8, 88%). All of the 27 (100%) intimal calcifications were present in the progressive atherosclerotic lesions ( P<0.001), whereas only 3/8 (38%) internal elastic lamina calcifications and 4/6 (67%) adventitial calcifications were associated with progressive plaques. Arteries with intimal calcification had more severe luminal stenosis than those without (46% versus 21%; P<0.001). Conclusions- Our histological findings indicate that the presence of intracranial artery calcification has 3 patterns, including intimal, internal elastic lamina, and adventitial calcifications. But only intimal calcification is related with progressive atherosclerotic lesions, indicative of a proxy for intracranial atherosclerosis.

A large and aggressive fibromatosis in the axilla: a rare case report and review of the literature.

Aggressive fibromatosis (AF) is a rare benign tumor, which occurs in the deep part of bone and muscle fibrous tissue. Clinical and pathological features can be challenging for definitive diagnosis. Here, we report a rare case of a large AF in the axilla. Interestingly, 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography showed significant increase in standard uptake value. Surgical resection yielded a spindle cell tumor likely of fibromatosis origin which was positive for ß-catenin expression.

Postmortem Study of Validation of Low Signal on Fat-Suppressed T1-Weighted Magnetic Resonance Imaging as Marker of Lipid Core in Middle Cerebral Artery Atherosclerosis.

BACKGROUND AND PURPOSE: High signal on T1-weighted fat-suppressed images in middle cerebral artery plaques on ex vivo magnetic resonance imaging was verified to be intraplaque hemorrhage histologically. However, the underlying plaque component of low signal on T1-weighted fat-suppressed images (LST1) has never been explored. Based on our experience, we hypothesized that LST1 might indicate the presence of lipid core within intracranial plaques. METHODS: 1.5 T magnetic resonance imaging was performed in the postmortem brains to scan the cross sections of bilateral middle cerebral arteries. Then middle cerebral artery specimens were removed for histology processing. LST1 presence was identified on magnetic resonance images, and lipid core areas were measured on the corresponding histology sections. RESULTS: Total 76 middle cerebral artery locations were included for analysis. LST1 showed a high specificity (96.9%; 95% confidence interval, 82.0%-99.8%) but a low sensitivity (38.6%; 95% confidence interval, 24.7%-54.5%) for detecting lipid core of all areas. However, the sensitivity increased markedly (81.2%; 95% confidence interval, 53.7%-95.0%) when only lipid cores of area ≥0.80 mm(2) were included. Mean lipid core area was 5× larger in those with presence of LST1 than in those without (1.63±1.18 mm(2) versus 0.32±0.31 mm(2); P=0.003). CONCLUSIONS: LST1 is a promising imaging biomarker of identifying intraplaque lipid core, which may be useful to distinguish intracranial atherosclerotic disease from other intracranial vasculopathies and to assess plaque vulnerability for risk stratification of patients with intracranial atherosclerotic disease. In vivo clinical studies are required to explore the correlation between LST1 and clinical outcomes of patients with intracranial atherosclerotic disease.

Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy.

To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

In Vitro Assessment of Histology Verified Intracranial Atherosclerotic Disease by 1.5T Magnetic Resonance Imaging: Concentric or Eccentric?

BACKGROUND AND PURPOSE: Clinical trial studies show that plaque eccentricity (symmetry) is among the plaque features that have been associated with more frequent cerebrovascular events. Plaque eccentricity of intracranial atherosclerotic disease is unclear because of lacking of cerebral artery specimens. METHODS: 1.5T magnetic resonance imaging was performed in the postmortem brains to scan the cross sections of middle cerebral artery. Plaque eccentricity of histology-verified middle cerebral artery atherosclerosis was calculated on T1-weighted fat-suppressed sequence. RESULTS: Validated by histology, concentric atherosclerotic plaques were identified in 46 middle cerebral arteries (63.9%) on magnetic resonance imaging and eccentric plaques in 26 arteries (26.1%). Eccentric plaques showed higher maximum wall thickness and lower minimum wall thickness than concentric plaques (both P<0.001). Plaque burden and brain infarctions were similar between concentric and eccentric plaques. CONCLUSIONS: Intracranial atherosclerosis presents as eccentric or concentric in geometry, which may be not linked to intracranial plaque risk. Further in vivo imaging studies are needed to identify morphological features of intracranial plaques and to verify its association with brain infarctions.

An effective initial polytherapy for children with West syndrome.

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

NEDD9 is a positive regulator of epithelial-mesenchymal transition and promotes invasion in aggressive breast cancer.

Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. The latest studies revealed that aggressive breast cancer, especially the triple-negative breast cancer (TNBC) subtype was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types. In this study, we wished to discern the role of NEDD9 in breast cancer progression and to investigate the molecular mechanism by which NEDD9 regulates EMT and promotes invasion in triple-negative breast cancer. We showed that expression of NEDD9 was frequently upregulated in TNBC cell lines, and in aggressive breast tumors, especially in TNBC subtype. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to a string of events including the trigger of EMT, activation of ERK signaling, increase of several EMT-inducing transcription factors and promotion of their interactions with the E-cadherin promoter. Data presented in this report contribute to the understanding of the mechanisms by which NEDD9 promotes EMT, and provide useful clues to the evaluation of the potential of NEDD9 as a responsive molecular target for TNBC chemotherapy.

Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) and CD74 emerge as important players in pathogenesis and angiogenesis of several types of malignant tumors. The purpose of this study was to evaluate the expression of MIF and CD74 in cervical squamous cell carcinoma and explore the potential roles they play in cervical tumor angiogenesis. METHODS: Macrophage migration inhibitory factor and CD74 expression was assessed by immunohistochemistry in 209 cases with various degrees of cervical epithelial lesions, including 40 normal cervical epithelia, 43 mild cervical intraepithelial neoplasia 1 (CIN 1), 41 moderate-severe cervical intraepithelial neoplasia (CIN 2 to 3), and 85 cervical squamous cell carcinomas (SCCs). CD34 staining was used for counting microvessel density. Semiquantitative reverse transcription polymerase chain reaction and Western blot were used to detect messenger RNA and protein levels of MIF and CD74 in normal and malignant cervical tissues and cervical cancer cell lines SiHa and C-33A. The concentration of vascular endothelial growth factor (VEGF) in the conditioned media of cervical cancer cells was analyzed by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemical analysis showed that MIF and CD74 expression was significantly higher in CIN than in the normal samples and higher in SCC than in CIN. The overexpression of MIF was correlated with deep stromal infiltration but not with the other clinicopathologic features of SCC. Correlation analyses revealed that MIF was positively related to CD74, and both protein levels were associated with microvessel density. Exogenous MIF induced VEGF secretion in SiHa and C-33A cells in a dose-dependent manner, which can be inhibited by MIF-specific inhibitor (ISO-1) or anti-CD74 antibody. CONCLUSION: Overexpression of MIF and CD74 in SCC and its precancerous lesions and the up-regulation of VEGF secretion in cervical cancer cells indicate that MIF and CD74 may play critical roles in the pathogenesis and angiogenesis of cervical cancer.

BRAF point mutations in primary melanoma show different prevalences by subtype.

To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.

[Effects of mtDNA deletion associated with abnormal expression in rat cochlear with presbycusis].

OBJECTIVE: To investigate the effects of the common deletion (4834-bp) of mitochondrial DNA (mtDNA) in rat cochlear with presbycusis. METHODS: The mtDNA 4834-bp deletion was analyzed by PCR. The mitochondrial-encoded cytochrome c oxidase subunit I (COXI) transcript level and cytochrome c oxidase (COX) activity were measured by RT-PCR and histochemical methods respectively. RESULTS: The 4834-bp deletion occurred in all the senescent rat cochlear. The COXI transcript level was decreased associated with the decline of COX activity. CONCLUSION: The mtDNA 4834-bp deletion presented in the rat cochlear with presbycusis, which lead to the decrease of COXI transcript level and COX activity, may play an important role in the pathogens of presbycusis.

[Research into the human leucocyte antigen I deletion and local lymphocytes infiltration in laryngeal carcinoma].

OBJECTIVE: To detect the deletion of human leucotyte antigen (HLA) class I antigen expression in laryngeal carcinoma tissue and discuss the relationship between its expression and tumor infiltrating lymphocyte (TIL) cell infiltration or/and malignancy of tumor cell. METHODS: From Feb 2001 to May 2001 specific mouse antihuman HLA class I monoclonal antibody was combined to examined tissue, 64 samples of laryngeal carcinoma were detected by streptavidin-peroxidase (SP) method immunohistochemistry. RESULTS: All of 64 cases, 57 were positive HLA class I antigen and 7 were negative, the negative expression rate was 10.9% (7/64). CD3+ and CD8+ T cell infiltrated in HLA class I positive tumor mass were significantely more than those in negative tissue. the malignant degree elevated along with the declination of HLA class I antigen expression. By 3 years follow up, the mortalitywas not statistically significant in both HLA- group and HLA+ group (P > 0.05). CONCLUSION: There is deletion of HLA class I antigen in laryngeal tissue, which favours penetration of cytotoxic lymphoid cells into tumor mass; alteration in HLA class I expression may be used by cancer cells to avoid immune surveillance.