[Mechanism of pepsin promoting lingual tonsil hypertrophy by stimulating macrophage].

Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ2=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.

[Study on the correlation between adenoid hypertrophy and laryngopharyngeal reflux in children].

Objective:To discuss the correlation between adenoid hypertrophy and laryngopharyngeal reflux in children, and to determine the accuracy of reflux symptom index(RSI) and reflux finding score(RFS) in predicting adenoid hypertrophy and laryngopharyngeal reflux(LPR). Method:Assessment of RSI and RFS was performed in 71 children with adenoid hypertrophy who underwent surgery.The adenoid biopsy specimens were examined by pepsin immunohistochemical staining. According to the positive results of pepsin staining to evaluate the sensitivity and specificity of RSI and RFS to predict LPR. Result:Among the 71 children with adenoid hypertrophy, RSI was greater than 13 points in 4 cases (5.63%), RFS was greater than 7 points in 26 cases (36.62%), and 1(1.41%) was positive in both scores. Pepsin expression was detected in 52 cases of adenoid hypertrophy tissues, with a total positive rate of 73.24% (52/71),most were strong positive（15/71,21.13%）and positive（23/71,32.39%）. The higher the adenoid hypertrophy grade, the higher the expression level of pepsin (r=0.476, P<0.01).Define the positive rate of pepsin as the gold standard for the diagnosis of LPR, the sensitivity and specificity of RSI and RFS were 5.77%,34.62% and 94.74%,57.89% respectively. Pepsin staining intensity was positively correlated with troublesome or annoying cough（r=0.356, P=0.002）and was negatively correlated with ventricular obliteration（r=－0.212，P=0.038）. Conclusion:There is a correlation between adenoid hypertrophy and LPR in children，LPR plays an important role in the development of adenoid and the role and mechanism of pepsin in adenoid hypertrophy needs further studyAs the low sensitivity of RSI and RFS, it is not suitable for the screening of adenoid hypertrophy in children with LPR. Children with adenoid hypertrophy cough for a long time and the laryngoscopy shows the ventricular obliteration, the presence of LPR should be warned.

[Expression and significance of pepsin in lingual tonsil hypertrophy].

Objective: To discuss the relationship between lingual tonsil hypertrophy and laryngopharyngeal reflux. Methods: Ninety-two patients who received throat surgery in Nanfang Hospital between October 2015 and October 2016 were enrolled. Twenty-six healthy volunteers were recruited as normal controls. All participants were assessed with the reflux finding score(RFS) and the size of lingual tonsils were evaluated using a clinical grading system proposed by Friedman under electronic laryngoscope. The score of reflux symptom index(RSI), personal history and medical history were gathered. Biopsy specimens of lingual tonsils were taken from all participants for the immunohistochemical stain of pepsin.SPSS 19.0 software was used for statistical analysis. Results: There were 46.2% (12/26) pepsin-positive and 53.8% (14/26) pepsin-negative volunteers in normal controls. There were 87.0% (80/92) pepsin-positive and 13.0% (12/92) pepsin-negative patients in study group. The severity of lingual tonsil hypertrophy and expression intensity of pepsin in patients were significantly higher in volunteers (Z=-3.636, Z=-5.273, P<0.01). The severity of lingual tonsil hypertrophy was positively associated with the pepsin level in patients (r=0.556, P<0.01). The patients with pepsin-positive expression showed significant correlation between lingual tonsil hypertrophy and the positive rate of RSI and RFS (r=0.258, r=0.225, P<0.05). Analysis of correlated factors indicated that lingual tonsil hypertrophy was associated with smoking (χ(2)=8.502, P<0.05). Conclusions: The expression of pepsin can be detected in lingual tonsil tissues. The lingual tonsil hypertrophy is closely related to laryngopharyngeal reflux.

[The expression and significance of pepsin in laryngeal carcinoma].

OBJECTIVE: To evaluate the relationship between pepsin induced by laryngopharyngeal reflux and laryngeal carcinoma. METHODS: Patients with vocal cord leukoplakia(n=18) and laryngeal carcinoma(n=21) encountered in Nanfang Hospital between December 2012 and April 2014 were included and sixteen healthy volunteers were recruited as control. Laryngeal biopsy specimens were taken from the patients with laryngeal carcinoma, or vocal cord leukoplakia and control subjects for the immunohistochemical study of pepsin. The correlation between pepsin expression and reflux events of 24 hour multichannel intraluminal impedance-pH monitoring (MII-pH) was analyzed. RESULTS: The patients with laryngeal carcinoma showed the highest expression of pepsin, followed by the patients with vocal cord leukoplakia and control subjects, with significant difference among the three groups (in strong positive expression, the constituent ratio of each group are 0/16、1/18 and 4/21, P<0.01). The presence of pepsin was associated with upright and total laryngopharyngeal acid reflux (P<0.05), including acid reflux episodes, the percentage of times that the pH was below four, the percentages of acid reflux time and average acid removal time. There was a significant correlation between the pepsin level and the esophageal acid reflux parameters (P<0.05) except supine the percentage of time that the pH was below four. CONCLUSIONS: Pepsin expression in laryngeal tissue increases in patients with vocal cord leukoplakia and laryngeal carcinoma, contributing to the development of laryngopharyngeal carcinogenesis.

[Up-regulation of DLK1 in non-small cell lung cancer and the relevant molecular mechanism].

OBJECTIVE: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism. METHODS: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLC patients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples. RESULTS: Among the 102 squamous cell carcinoma (SCC) tissue specimens and their adjacent normal bronchial epithelia, DLK1 was up-regulated in 72 and 37 samples, respectively (P=0.001), and among 102 adenocarcinomas (ADC) tissues and their adjacent alveolar tissues, DLK1 was up-regulated in 77 and 7 samples, respectively (P<0.001). In addition, overexpression of DLK1 was significantly associated with histological type, clinical stage and tumor size of NSCLC (P<0.05 for all). The expression of DLK1protein was inversely correlated with its promoter methylation (P<0.05). CONCLUSION: DLK1 expression is up-regulated in NSCLCs, which may be due, at least in part, to the DNA hypomethylation in the promoter region of theDLK1 gene.

Rapid reversal of coagulopathy in warfarin-related intracranial haemorrhages with prothrombin complex concentrates.

We report our initial experience using Profilnine SD, a 3-Factor prothrombin complex concentrate (PCC) in combination with fresh frozen plasma and vitamin K in seven patients admitted to our neurointensive care unit with oral anticoagulation therapy-related intracranial haemorrhage over a six-month period, to achieve rapid normalisation of the international normalised ratio (INR) and allow surgical evacuation when indicated. Four patients presented with subdural haematomas while three had intracerebral haematomas. Six of seven patients had admission INR in the appropriate therapeutic range for oral anticoagulation therapy. The median dose of PCC administered was 28.5 IU/kg body weight (interquartile range 21.3 to 38.5 IU/kg). All four patients with subdural haematoma underwent surgical evacuation once INR was less than 1.5. Median time from computed tomography diagnosis to surgery was 275 minutes (range 102 to 420 minutes). The median time to INR normalisation post-PCC administration was shorter, at 85 minutes (range 50 to 420 minutes) for the four patients who survived, versus 10 hours (range 9 to 44 hours) in the three patients who died. Two of the three patients who died had haematoma increase, worsening midline shift and subfalcine herniation, leading to withdrawal of therapy. Prothrombin complex concentrates should be considered for use in the urgent reversal of INR in oral anticoagulation therapy-related intracranial haemorrhage, potentially halting haematoma expansion and expediting urgent neurosurgical intervention, although data from randomised controlled trials is still lacking. The literature supporting the use of PCC is reviewed and a protocolised emergent treatment algorithm is proposed, which may help achieve earlier consistent normalisation of the INR.

Laparoscopic surgery for ulcerative colitis - a meta-analysis.

OBJECTIVE: To assess the safety and feasibility of laparoscopic surgery for patients with ulcerative colitis. METHODS: A search of published studies in English between January 1992 and September 2005 was obtained, using the MEDLINE and PubMed databases and the Cochrane Central Register of Controlled Trials. Two independent assessors reviewed the studies using a standardized protocol. Where raw data, means and standard deviations were available, meta-analysis was performed using the Forest plot review. Studies where medians and ranges were presented were separately analysed. RESULTS: The duration of surgery for laparoscopic and open procedures were similar (weighted mean difference 62.92 min, P = 0.19). Patients were able to tolerate oral intake significantly earlier, with a weighted mean difference of 1.39 days (P = 0.002), but recovery of bowel function was similar (weighted mean difference 0.73 days, P = 0.36). The length of hospital stay was shorter for patients who had undergone laparoscopic surgery, with a weighted mean difference of 2.64 days (P = 0.003). The complication rate was higher in open colectomy, compared to laparoscopic colectomy (67.6%vs 39.7%, P = 0.005). For restorative proctocolectomy, complication rates were comparable between the laparoscopic and open groups (P = 0.25). CONCLUSIONS: The time taken to perform laparoscopic surgery is similar to open surgery. Patients are able to tolerate oral intake earlier, and have a shorter hospitalization. Laparoscopic colectomy was safer compared to the open procedure, but both were equally safe for patients who had restorative proctocolectomy. Thus, laparoscopic surgery for ulcerative colitis is both safe and feasible.

Which is the optimal bowel preparation for colonoscopy - a meta-analysis.

OBJECTIVE: To assess which bowel preparation agent is most effective. METHODS: A search of randomized trials between January 1990 and July 2005 was obtained, using MEDLINE and PubMed databases, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the Forest plot review. RESULTS: Sodium phosphate (NaP) was more effective in bowel cleansing than polyethylene glycol (PEG) - odds ratio 0.75 (95%CI: 0.65-0.88; P = 0.0004); and sodium picosulphate (SPS) - odds ratio 0.52 (95%CI: 0.34-0.81; P = 0.004). PEG and SPS were comparable in bowel cleansing ability, odds ratio 1.69 (95%CI: 0.92-3.13; P = 0.09). NaP was more easily completed by patients compared to PEG, odds ratio 0.16 (95%CI: 0.09-0.29; P < 0.00001). More patients were able to complete SPS than PEG, but this was not statistically significant - odds ratio 0.56 (95%CI: 0.28-1.13; P = 0.11). NaP and PEG were comparable in terms of adverse events, odds ratio 0.98 (95%CI: 0.82-1.17; P = 0.81), although NaP resulted in more asymptomatic hypokalaemia and hyperphosphataemia. NaP and SPS appeared to have similar incidence of adverse events. PEG resulted in more adverse events than SPS, odds ratio 3.82 (95%CI: 1.60-9.15; P = 0.003). CONCLUSIONS: NaP was more effective in bowel cleansing than PEG or SPS and was comparable in terms of adverse events. Patients have more difficulty completing PEG than NaP and SPS. Biochemical changes associated with a small-volume preparation like NaP, albeit largely asymptomatic, mandate caution in patients with cardiovascular or renal impairment.

Prospective, randomized trial comparing diathermy and Harmonic Scalpel hemorrhoidectomy.

PURPOSE: The aim of this study was to compare diathermy and Harmonic Scalpel hemorrhoidectomy. METHODS: Fifty consecutive patients were randomly assigned to 2 groups: Group 1 (diathermy) and Group 2 (Harmonic Scalpel). RESULTS: The median duration of surgery was 10 minutes for both groups. The median number of pethidine injections used for both groups was zero. The median number of oral analgesic tablets taken was 13 by Group 1 and 14 by Group 2 patients. The median number of tubes of lidocaine jelly used was two by Group 1 and three by Group 2. There was no statistical difference between pain scores recorded by both groups. Five patients in Group 1 developed posthemorrhoidectomy bleed vs. one patient in Group 2 (P = NS). CONCLUSION: Hemorrhoidectomy by Harmonic Scalpel is comparable to diathermy hemorrhoidectomy in terms of postoperative pain and complications.