[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

[Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Methods: A total of 12 specimens were collected, which were surgically resected and verified as MEITL by postoperative pathology, immumohistochemical staining and gene rearrangement at the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018, and all of these had complete clinical and pathological data. The MEITL cases were reviewed to compare the clinicopathological characteristics, including morphologic and immunophenotypic features and followed up by telephone and clinic visit. Results: All the cases were diagnosed with MEITL. There were 8 males and 4 females. Male to female ratio was 2∶1, at a median age of 54 years. The sites of involvement included jejunum (4 cases), ileum (5 cases), duodenum (1 case), ileocecal junction (1 case) and rectum (1 case). The neoplastic cells were monotonous of small to intermediate cells in size with round to slightly irregular nuclei in 11 cases. The immunophenotyping showed that CD3 (12/12), CD8 (11/12), CD43 (11/12), CD56 (11/12), TIA-1 (12/12) were positive; CD5 (12/12), Gran B (9/12), and perforin (7/12) were negative. Two cases aberrantly expressed the B-cell marker CD20. A high proliferation index was demonstrated by Ki-67 immunostaining. In situ hybridization for EBER was all negative(12/12). The whole exome sequencing(WES) mutational landscape of MEITL was remarkably homogeneous, showing significantly enriched clusters among histone modifier genes, JAK-STAT and MAPK-signal pathways. Histonelysine N-methytransferase SETD2 gene was mutated in 2/4 tumors. All the patients analyzed harbored at least one mutation in the JAK-STAT signal pathway, including STAT5B (2/4), JAK3 (3/4) and STAT5A (2/4). Furthermore, frequent alterations (TP53) were observed in the MAPK pathway in 3/4 of MEITL cases. The CNV analysis derived from WES data identified multiple regions of frequent gains and losses. In particular, gains in 1q, 7q and 9q, and recurrent losses involving 7p and 8p were observed. Conclusions: MEITL is a rare and aggressive type of extranodal T-cell lymphoma. The differential diagnosis of MEITL includes EATL, extranodal NT/T-cell lymphoma and other types of PTCL. Diagnosis should be correlated to clinical symptoms while the final diagnosis is mainly based on the pathological features, immunophenotypes and genetic testing.

[Bronchiolar adenoma: a clinicopathological analysis of 15 cases].

Objective: To study the clinicopathological characteristics, diagnosis and differential diagnosis of bronchiolar adenoma (BA). Methods: Fifteen cases of BA were collected from the First Affiliated Hospital of Nanjing Medical University, from January 2016 to October 2019. The clinical data, imaging examination, morphology, immunostaining and molecular changes were retrospectively analyzed. Results: There were 3 males, 12 females, most of the patients were female, mainly in middle-aged to elderly (51-77 years). Three had smoking history. The patients usually had no clinical symptoms. Imaging findings were ground-glass and/or lobulated nodules. Grossly, the tumors were gray-whitish, taupe solid or focally microcystic nodules with distinct boundary but no capsule. The maximum diameter was 0.4-2.5 cm (mean 1.0 cm). Histologically, there were glandular, papillary, or flat patterns that were composed of basal cells, mucous cells, ciliated cells and type Ⅱ pneumocytes, some of which showed basal cell proliferation and squamous cell metaplasia. However, there were some cases with few or even without mucous and/or ciliated cells. Immunostaining highlighted the continuous basal cell layer (positive for p63, p40 and cytokeratin 5/6), which was the most important diagnostic evidence. Genetic tests did not show mutation in BRAF or EGFR genes. All patients were followed up for 1-41 months, and they were without recurrence or metastasis. Conclusions: BA is a benign neoplasm that develops in the peripheral lung with good prognosis. Definite diagnosis is very crucial for surgical treatment, especially in frozen consultation. Immunohistochemistry will be helpful if necessary.

First co-infection case of melioidosis and Japanese encephalitis in China.

BACKGROUND: Melioidosis is endemic in Southeast Asia and northern Australia. Infection usually follows percutaneous inoculation or inhalation or ingestion of the causative bacterium, Burkholderia pseudomallei, which is present in soil and surface water in endemic regions. Japanese encephalitis (JE) is a vector-borne viral zoonosis caused by Japanese encephalitis virus (JEV), leading to epidemic encephalitis in Southeast Asia. Both B. pseudomallei and JEV have spread dominantly in the Hainan and Guangdong provinces in China. Here we reported the first case of co-infection of B. pseudomallei and JEV, which was discovered in Huizhou in the Guangdong province in June 2016. CASE PRESENTATION: A 52-year-old man was admitted to the hospital with acute febrile illness and headache, diagnosed as respiratory infection, central nervous system (CNS) infection, septicemia, and hepatic dysfunction. Based on B. pseudomallei-positive blood and cerebrospinal fluid (CSF) cultures, the patient was diagnosed with melioidosis and treated aggressively with antibiotics. However, the patient failed to make a full recovery. Further laboratory tests focused on CNS infection were conducted. The co-infection of B. pseudomallei and JEV was confirmed after the positive IgM antibodies of JEV were detected in both CSF and blood. After diagnosis of co-infection with B. pseudomallei and JEV, the patient was provided supportive care in hospital and recovered after approximately 3 weeks. CONCLUSION: Given the possibility of co-infection of B. pseudomallei and JEV, as well as variable case presentations, it is critical to enhance the awareness, detection, and treatment of co-infection in regard to melioidosis.

Effects of left ventricular assist device (LVAD) placement on myocardial oxidative stress markers.

PURPOSE: The primary purpose of this study was to examine the changes in myocardial oxidative stress during the support of a left ventricular assist device (LVAD). METHODS: Myocardial tissue was collected from the lower left ventricle of 15 adult subjects with class IV heart failure (HF) during LVAD placement (n=9) or LVAD removal (Post-LVAD; n=6). Each tissue sample was separated into cytosolic and myofibrillar subfractions and analysed for protein content and carbonylation. RESULTS: The myofibrillar proteins in the HF subjects had a significantly lower (p=0.008) level of protein carbonylation when compared to the myofibrillar proteins in Post-LVAD patients at 1.630±0.277 and 3.075±0.413 optical density, respectively. The level of protein carbonylation in myosin and actin were lower in HF (myosin: 1406.22±218.45, actin: 436±79.72 optical density) subjects compared to Post-LVAD (myosin: 2280.5±441.26, actin: 804.67±155.71 optical density) subjects (p=0.035 and p=0.018, respectively). However, once the extent of carbonylation in the myosin and actin bands were normalised to the amount of protein content, all significant difference was lost (HF moysin: 1823.89±413.42, Post-LVAD myosin: 1330.33±297.10 optical density, p=0.199 and HF actin: 3755.78±349.59, Post-LVAD actin: 4402.83±666.51 optical density, p=0.182). There was no significant difference in the cytosolic subfractions before or after normalisation of protein content. CONCLUSION: Carbonylation is elevated in the myocardium of HF and Post-LVAD subjects and it appears that LVAD support does not affect the level of myocardial oxidative stress.

Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells.

It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial.

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

Improved liquid crystal pretilt angles by patterned dual alignment coating structures.

The pretilt angles for the optically compensated bend (OCB) mode liquid crystals have been improved using novel patterned dual alignment coating structures in this study. The transition from the splay configuration to the bend configuration can thus be effectively reduced. The dual alignment coating structures consisted of a horizontal alignment polyimide (PI) and a patterned vertical alignment liquid crystal polymer (LCP). Three patterning masks were designed for the photolithography process. The pretilt angles were demonstrated to be increased to 34 degrees for the triangle lattice array-patterned cells. It became 31 degrees for the square lattice array-patterned cells, and 24 degrees for the honeycomb lattice array-patterned cells. The improved pretilt angles were illustrated by the force balance model that can be predicted by the LCP area ratio. The effective control over the pretilt angle could improve the response time to 2 ms when the voltage was ramped up to 5.5 V for the OCB mode liquid crystal devices.

Plasma indoxyl sulfate concentration predicts progression of chronic kidney disease in dogs and cats.

Indoxyl sulfate is a protein-bound uremic toxin that increases as the severity of impaired renal function increases in humans, laboratory animals, dogs and cats. An elevation of indoxyl sulfate is related to prognosis among people with chronic kidney disease. However, whether indoxyl sulfate is able to predict the progression of chronic kidney disease in dogs and cats has not been previously studied. In the present study, 58 cats and 36 dogs with chronic kidney disease were enrolled. Plasma indoxyl sulfate was measured by high performance liquid chromatography. Renal progression was defined as an increase by one International Renal Interest Society (IRIS) stage and/or a rise in serum creatinine concentration of 0.5mg/dL during the same stage within a 3-month period. Compared with the non-progression groups, across different stages of renal failure, the baseline plasma indoxyl sulfate concentration was increased in the renal progression group (P<0.05), especially for IRIS stages 2 and 3 animals. The area under the receiver operator characteristic curves of indoxyl sulfate, when predicting renal progression, was above 0.75 for both dogs and cats. Indoxyl sulfate concentrations were also correlated with the increase of blood urea nitrogen, serum creatinine, and phosphate and the decrease of hematocrit among cats; while in dogs, concentrations were only correlated with the increase of phosphate concentrations. Indoxyl sulfate served as a biomarker of progression risk in dogs and cats with chronic kidney disease.

Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients.

The purpose of this study was to investigate the clinical usefulness of the color Doppler vascularity index (CDVI) in patients with colon cancer before surgery. Forty-four patients with sonographically visible tumor mass of colon cancer were investigated. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). The correlation between the CDVI and clinicopathological factors, mode of recurrence, and patient survival was studied. For comparison, microvessel density (the mean number of microvessels in three areas of highest vascular density at x200 magnification) of the tumors of these 44 patients was also evaluated by using immunohistochemical staining of surgical specimens with anti-CD34. The microvessel density was not correlated with Dukes' classification, clinicopathological factors, and survival. The CDVI was significantly higher in the patients with lymph node metastases and vascular invasion than in those without such metastases and invasion (P = 0.006 and P = 0.0098, respectively). Moreover, in patients with a high CDVI (> 15%) and positive vascular invasion, survival was significantly poorer than in those with low CDVI (< or = 15%) and negative invasion (P = 0.0037 and 0.0039, respectively). Multivariate analysis indicated that liver metastasis, vascular invasion, and CDVI are independent prognostic factors in the patients with colon cancer. According to the mode of recurrence in 36 patients who underwent curative resection, the frequency of the distant organ recurrence was significantly higher in the high CDVI group (40%) than in the low CDVI group (0%). The CDVI is a good preoperative indicator of recurrence and patient survival in colon cancer. Thus, the CDVI may be helpful in stratifying patients for adjuvant therapy.

Characterization of the memory gene dunce of Drosophila melanogaster.

The dunce (dnc) gene of Drosophila melanogaster encodes cAMP phosphodiesterase (PDEase) and is required for learning/memory and female fertility. The gene is structurally complex, demonstrated in part by Northern blotting experiments which detected multiple RNAs ranging in size from 4.2 to 9.6 kb (1 kb = 10(3) bases or base-pairs). To characterize these RNAs and to understand their sequence heterogeneity, we isolated and analyzed 29 new and independent cDNA clones representing the dnc RNAs. Restriction mapping, hybridization analysis and sequence determination of these cDNA clones and the corresponding genomic exons resolved these into six different classes. Exons defined by the cDNA clones are distributed over more than 148 kb of genomic DNA, with some exons being used alternatively among the RNAs. The RNAs are transcribed from at least three initiation sites: two of these were mapped by parallel S1-nuclease and primer extension experiments. In addition, some of the heterogeneity is generated by using varying lengths of a 3'-untranslated trailer sequence. Altogether, the results indicate that the size and sequence heterogeneity of dnc transcripts results from transcription initiation at multiple sites, alternative splicing, and processes which generate different 3' ends. The existence of multiple protein products is suggested by the alternative use of exons which code for portions of the open reading frame. The protein variation potentially includes N-terminal differences coded for by transcript-specific 5' exons and internal differences arising from the optional inclusion of a 39 base-pair exon and from the alternative use of two 3' splice sites separated by six base-pairs. Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation. The results suggest that the remarkable structural complexity of dnc may reflect an intricate control of the spatial and/or temporal expression of various isoforms of cAMP PDEase.

The Shatin community mental health survey in Hong Kong. II. Major findings.

A large-scale community survey in Shatin, Hong Kong, is presented with a modified two-phase design using flagged and nonflagged subsamples. A modified Self-Reporting Questionnaire and the Diagnostic Interview Schedule (version III) were used as the screening and diagnostic instruments, respectively. Lifetime rates for 19 Diagnostic Interview Schedule/DSM-III diagnoses are presented. The most common diagnoses in Shatin were tobacco dependence, generalized anxiety disorder, alcohol abuse and/or dependence, all phobias, and dysthymic disorder. The male-predominant disorders were tobacco dependence, alcohol abuse/dependence, pathological gambling, and antisocial personality. The female-predominant disorders were generalized anxiety disorder, all phobias, dysthymic disorder, major depressive disorder, obsessive-compulsive disorder, and bereavement.

Synthesis and Electrochemical Properties of Nitrogen-Doped Graphene (NG)/Nickle Oxide (NiO) Nanocomposite for Supercapacitor.

A novel nitrogen-doped graphene (NG)/nickle oxide (NiO) nanocomposite was synthesized by a facile two-step method, where NiO particles were dispersed on the surface of NG. The NG/NiO nanocomposite is characterized by using field-emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Raman spectroscopy. The electrochemical properties of NG/NiO nanocomposite have been studied using cyclic voltammetry (CV), galvanostatic charge/discharge and electrochemical impedance spectroscopy (EIS) techniques. Compared with the nitrogen-doped graphene, the electrode prepared by NG/NiO nanocomposite has a mass specific capacitance of 342 F g(-1) at scan rate of 5 mV s(-1), which is much higher than that of nitrogen-doped graphene (NG). The galvanostatic charge/discharge results show this new kind nanocomposite has high specific capacitance with 320 F g(-1) in the range of 0.1-0.5 V at a current density of 1 A g(-1). The enhanced supercapacitive performance of NG/NiO nanocomposite suggesting its promising potential in supercapacitors.

Glypican 3 and glypican 4 are juxtaposed in Xq26.1.

Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) gene cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS; ). The next centromeric gene detected is another glypican, glypican 4 (GPC4), with its 5' end 120763bp downstream of the 3' terminus of GPC3. One recovered GPC4 cDNA with an open reading frame of 1668nt encodes a putative protein containing three heparan sulfate glycosylation signals and the 14 signature cysteines of the glypican family. This protein is 94.3% identical to mouse GPC4 and 26% identical to human GPC3. In contrast to GPC3, which produces a single transcript of 2.3kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses show that GPC4 produces two transcripts, 3.4 and 4.6kb, which are very widely expressed (though at a much higher level in fetal lung and kidney). Interestingly, of 20 SGBS patients who showed deletions in GPC3, one was also deleted for part of GPC4. Thus, GPC4 is not required for human viability, even in the absence of GPC3. This patient shows a complex phenotype, including the unusual feature of hydrocephalus; but because an uncle with SGBS is less affected, it remains unclear whether the GPC4 deletion itself contributes to the phenotype.

Sleep paralysis in Chinese: ghost oppression phenomenon in Hong Kong.

Despite reports of wide variation in the prevalence of sleep paralysis among different ethnic groups, there has never been any study in Chinese. In Hong Kong, a condition known as ghost oppression is descriptively identical to sleep paralysis. To examine this phenomenon, the response of 603 undergraduate students to a questionnaire were analyzed. Thirty-seven percent had experienced at least one attack of ghost oppression. There was no sex difference in the prevalence, and the peak age of onset was at the range of 17-19 for both sexes. A strong familial association was found and 20% of subjects reported a positive family history. Over one sixth of the subjects identified sleep disruption and stress as precipitating events.

In vitro surface characterization of a biological patch fixed with a naturally occurring crosslinking agent.

The study was designed to characterize the surface properties (including water contact angle, surface tension, protein adsorption, platelet adhesion, and cellular compatibility) of a biological patch fixed with genipin, a naturally occurring crosslinking agent. Fresh and glutaraldehyde-fixed counterparts were used as controls. It was found that both glutaraldehyde and genipin are effective crosslinking agents for biological tissue fixation. Fixation of biological tissue with glutaraldehyde or genipin significantly increased its hydrophilicity and surface tension and reduced its mol ratio of adsorbed fibrinogen to adsorbed albumin as well as the amount of adhered platelet. There were no significant differences in hydrophilicity, surface tension, the mole ratio of adsorbed fibrinogen to adsorbed albumin, and the amount of platelet adhesion between the glutaraldehyde- and genipin-fixed tissues. However, the cellular compatibilities of fresh and the genipin-fixed tissues were significantly superior to the glutaraldehyde-fixed tissue.