[Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease].

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3ß phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Epidemiology and risk factors for faecal extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) carriage derived from residents of seven nursing homes in western Shanghai, China.

Nursing homes (NHs) have been implicated as significant reservoirs of antibiotic-resistant organisms causing severe infectious disease. We investigated the prevalence and molecular epidemiology of, and risk factors for, faecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). A multicentre cross-sectional study was conducted in seven NHs in Shanghai between March 2014 and May 2014. Antimicrobial susceptibility testing and polymerase chain reaction were used to detect genes coding for ESBLs and carbapenemases. NH records at individual-resident level and facility level were examined for potential risk factors. Four hundred and fifty-seven Enterobacteriaceae isolates were collected of which 183 (46·92%) were colonized by ESBL-E. CTX-M enzymes (198/200, 99%) predominated, with CTX-M-14 (84/200, 42%) the most common types. Two carbapenemase producers harboured blaKPC-2. Resistance rates to carbapenems, TZP, AK, FOS, CL and TGC were low. History of invasive procedures [odds ratio (OR) 2·384, 95% confidence interval (CI) 1·318-4·310, P = 0·004], narrow-spectrum cephalosporins (OR 1·635, 95% CI 1·045-2·558, P = 0·031) and broad-spectrum cephalosporins (OR 3·276, 95% CI 1·278-8·398, P = 0·014) were independently associated with ESBL-E carriage. In conclusion, NH residents have a very high prevalence of faecal carriage of ESBL-E. Continuous and active surveillance is important, as are prudent infection control measures and antibiotic use to prevent and control the spread of these antibiotic-resistant strains.

Detection of aminoglycoside resistance related genes in multidrug-resistant Acinetobacter baumannii isolated from a single institute of Shanghai, China.

AIM: Aminoglycoside resistance is common in Acinetobacter baumannii. We investigated aminoglycoside resistance genes in clinical multidrug-resistant Acinetobacter baumannii strains isolated from the Chinese population. METHODS: One-hundred-and-seven strains of multidrug-resistant Acinetobacter baumannii were isolated from Ruijin Hospital in Shanghai, China. The minimum inhibitory concentrations (MICs) of amikacin, kanamycin, tobramycin, gentamicin, netilmicin and neomycin for these strains were determined with agar dilution method. 16S rRNA methylase genes and eight aminoglycoside modifying enzyme genes were tested via polymerase chain reaction. RESULTS: We found MICs of amikacin, kanamycin, tobramycin, gentamicin, netilmicin and neomycin in these strains with doses of ≥64 µg/mL, ≥64 µg/mL, ≥128 µg/mL, ≥128 µg/mL, ≥32 µg/mL and ≥8 µg/mL, respectively. Most of those strains showed a high-level resistance to aminoglycosides. ArmA was found in 90% (97/107) of the strains. Six modifying enzyme genes, including aac(6')-Ib, aac(6')-II, aac(3)-II, aac(3)-I, aph(3')-I and ant(3")-I were found with a positive rate of 47%, 50%, 28%, 31%, 93% and 96%, respectively. CONCLUSION: Multidrug-resistant Acinetobacter baumannii is highly resistant to aminoglycosides. Resistant genes could coexist in one strain, therefore, strict implementation of infection control measures is essential to avoid the rapid spread or outbreaks of these multidrug-resistant Acinetobacter baumannii in healthcare-associated facilities.

Retraction of articles by H. Zhong et al.

A series of 41 papers by H. Zhong et al. are retracted.

[An analysis of S/N ratio of the phonocardiogram exercise test].

Phonocardiogram exercise testing (PCGET) is a method through applying a phonocardiograph to evaluate cardiac contractility and the cardiac reserve. In order to test the certainty of PCGET method, a study on its S/N ratio was performed. Thirty volunteers performed PCGET. The average value of baseline amplitudes after exercise with respect to the average value of baseline amplitudes before exercise is 1.150; The average value of number of time of the S1 amplitude after exercise with respect to the S1 amplitudes before exercise is 10.57. The results suggest that PCGET has increased S/N ratio; introcardiac noise, noise from transmission of heart/thorax acoustic system, respiratory noise, muscle noise and ambient noise could not interfere in the application of PCGET. PCGET might be a noninvasive, convenient, and inexpensive technique to quantitatively evaluate cardiac reserve for abnormal or normal persons.

Electronic-Brain Medical Erudite: its past, present, and future.

Electronic-Brain Medical Erudite (EBME) is a large medical consultation system. Its core is the Enormous Knowledge Base of Disease Diagnosis Criteria (EKBDDC), which contains diagnostic criteria of 1,001 diagnostic entities and describes nearly 4,000 items of diagnostic indicators. EBME was implemented initially on a low-cost popular microcomputer, written in BASIC. This system can aid in the prompting of typical diseases and the teaching of diagnosis. We have performed a preliminary evaluation of EBME. Its performance on a series of trials with a total of 815 cases appeared qualitatively similar to that of the hospital clinicians. The diagnostic accordance rates were 89.7, 89.4, and 85% respectively. Recently, it is being transferred to a 386 microcomputer with a relational database, FoxBASE PLUS. This system will be improved, expanded, and connected with international medical information systems.

Idiopathic sudden hearing loss and disturbance of iron metabolism. A clinical survey of 426 cases.

The role of disturbances of the iron metabolism (DIM) in idiopathic sudden hearing loss (ISHL) was investigated in 426 patients with ISHL who received iron therapy, anti-DIM medication, vitamins, and a combined regimen in a randomized study which was stratified by stages and groups. Low concentrations of haemoglobin, serum iron, serum ferritin, and red cell basic ferritin as well as abnormal circadian variations in the serum iron level were observed. The results were significantly better in patients receiving iron therapy than in those receiving anti-DIM medication, vitamins, and the combined regimen. Hearing improvement was achieved in 53.26% of the patients whose treatment started later than 3 months after the onset of the disease. The clinical association of DIM and ISHL is discussed.

Sudden sensorineural hearing loss induced by experimental iron deficiency in rats.

The relation between iron deficiency (ID) and sudden sensorineural hearing loss (SSHL) was evaluated in the growing rats of three different experimental groups. Fourteen rats of 132 (10.61%) that were raised on a basic ID diet showed SSHL in varied extent, from moderate to profound. By contrast, none of 128 standard control and 126 anemic control rats that were fed with the final iron-supplemented diet showed any degree of SSHL. The main cochlear correlates of SSHL in ID rats were synchronous abnormalities of the iron-containing enzymatic activity in the whole cochlea, a significant reduction of spiral ganglion cells and a rapid involvement of stereocilia of the outer and inner hair cells. The results suggest that ID can play a major role in the pathogenesis of SSHL.

Red cell basic ferritin concentration in sensorineural hearing loss.

Red cell basic ferritin (RCBF) was measured in 62 healthy subjects with normal hearing and 224 patients with different kinds of sensorineural hearing loss, compared with serum ferritin, haemoglobin, serum iron and circadian variation in the serum iron levels. The results showed that the RCBF concentrations in most kinds of sensorineural hearing loss were significantly lower than those in normal hearing status. It is conceivable that the RCBF assay can be used to evaluate the adequacy of iron stores that are useful in times of urgent iron needs and to diagnose relative iron deficiency in those patients with some other normal laboratory assays related to iron metabolism.

Noise-induced hearing loss in iron-deficient rats.

The role of iron deficiency in noise-induced hearing loss (NIHL) was evaluated in 64 rats of four different experimental groups. Iron-deficient rats (ID-rats) and normal rats (N-rats) were simultaneously exposed to a steady state white noise (20-10,000 Hz) at 110 dB SPL for 30 min. Unexposed ID- and N-rats served as controls. In N-rats the temporary threshold shifts (TTS) would have completely disappeared if the animals were allowed to survive for 72 h. No permanent threshold shift (PTS) was seen in any of the N-rats. The ultrastructural correlates in N-rats are stereocilia disarray and mitochondria swelling in outer hair cells (OHCs). The TTS in ID-rats were larger than those in the N-rats, and most ID-rats with larger threshold shifts showed varying degrees of PTSs at 11 days post-exposure. The ultrastructural correlates of NIHL in ID-rats are obvious pathology of the stereocilia, such as segmental coalescence of stereocilia of many continuous OHCs and fusion of the tips of stereocilia of OHCs, and a significant reduction of mitochondria as well as slight degeneration of nucleus in the OHCs. It is concluded that iron deficiency can provide a pathological basis for NIHL.

Changes in the cochlear iron enzymes and adenosine triphosphatase in experimental iron deficiency.

The influences of iron deficiency on the cochlear iron enzymes and adenosine triphosphatase were studied in 68 iron-deficient rats and 68 control rats (normal and with chronic anemia). A disorderly or topographic distribution and reduction or disappearance of the cochlear succinic dehydrogenase and peroxidase reaction products were found in 37.8% of the rats fed on a basic iron-deficient diet for 14 to 100 days. The activity of cochlear sodium-potassium-dependent adenosine triphosphatase in iron-deficient rats was slightly increased, compared to that in normal controls. These results suggest that iron deficiency would produce significant abnormalities of succinic dehydrogenase and peroxidase activity, which in turn would disturb cell respiration and initiate peroxidative damage to the inner ear cells, result in sensorineural hearing loss, or provide a pathologic basis for cochlear deafness.

A scanning electron microscopic study of cochlear changes in iron-deficient rats.

The effects of iron deficiency on the cochlea were studied in growing rats fed with a basic iron-deficient diet for 80 days. The electrophysiological changes (auditory thresholds raised more than 15 dB) were observed in 47% of the cochleas of iron-deficient rats. When these organs of Corti were examined by scanning electron microscopy, abnormalities of outer or inner hair cells were found, as follows: (1) fusion and torsion of the stereocilia, (2) coalescence of adjacent stereocilia in the same row, (3) loss of sensory hair stiffness, and (4) loss of stereocilia. Within each lesion, the neighbouring supporting cells and their microvilli showed no damage. The findings indicate that cochlear impairment can be induced by iron deficiency. The peroxidative mechanisms responsible for the lesions of stereocilia in iron deficiency are discussed.

Iron deficiency and hearing loss. Experimental study in growing rats.

Cochlear changes were studied in 141 growing rats raised on a basic iron-deficient diet for 7-100 days; 130 rats served as normal or chronic anemia controls. Electrophysiological findings showed that the incidence of an auditory threshold elevation of more than 15 dB was 31.85% in the iron-deficient rats, but it was unchanged in all the control animals. The main cochlear histopathological changes induced by iron deficiency were strial atrophy and reduction of spiral ganglion cells. It is concluded that the observed anomalies may be attributed solely to iron deficiency of the cochlear tissue.