OBJECTIVE: To investigate the effects of Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat on rat spontaneous chronic pancreatitis and the pathological relationships between formulas and syndromes. METHODS: Fifty-seven male WBN/Kob rats at age of 4 weeks were divided into five groups: untreated group (n=18), Guizhi Decoction-treated group (n=9), Chaihu Guizhi Decoction-treated group (n=9), Xiaochaihu Decoction-treated group (n=9) and camostat-treated group (n=12). The rats in each group were fed with corresponding drugs for 12 weeks. The pancreatic wet weight and histopathological changes of pancreatic tissue were observed every four weeks. Meanwhile, the expression level of pancreatitis-associated protein (PAP) in pancreas was detected by RT-PCR technique and immunohistochemical method. RESULTS: In the untreated group, the histopathological changes in pancreas were observed in rats at 12-week age, while such changes were absent in the Guizhi Decoction-treated group. The histopathological changes in pancreas were quite remarkable in rats at 16-week age in both the Xiaochaihu Decoction-treated and the camostat-treated groups. The expression level of PAP mRNA was lower in the Guizhi Decoction-treated group than those in the other groups. The PAP expressions were absent in rats at 12-week age in the Guizhi Decoction-treated and the Chaihu Guizhi Decocion-treated groups. CONCLUSION: Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat are all beneficial to prevention and cure of chronic pancreatitis, and Guizhi Decoction is the most effective one. It is speculated that Taiyang exterior syndrome may be the pathogenesis of basic syndrome may be the pathogenesis of basic syndrome of spontaneous chronic pancreatitis, and the expression of PAP may be its pathological basis.

BACKGROUNDDual sensor (DS) for rate adaption was supposed to be more physiological. To evaluate its superiority, the DS (accelerometer [ACC] and minute ventilation [MV]) and normal sinus rate response were compared in a self-controlled way during exercise treadmill testing.

METHODSThis self-controlled study was performed in atrioventricular block patients with normal sinus function who met the indications of pacemaker implant. Twenty-one patients came to the 1-month follow-up visit. Patients performed a treadmill test 1-month post implant while programmed in DDDR and sensor passive mode. For these patients, sensor response factors were left at default settings (ACC = 8, MV = 3) and sensor indicated rates (SIRs) for DS, ACC and MV sensor were retrieved from the pacemaker memories, along with measured sinus node (SN) rates from the beginning to 1-minute after the end of the treadmill test, and compared among study groups. Repeated measures analysis of variance and profile analysis, as well as variance analysis of randomized block designs, were used for statistical analysis.

RESULTSFifteen patients (15/21) were determined to be chronotropically competent. The mean differences between DS SIRs and intrinsic sinus rates during treadmill testing were smaller than those for ACC and MV sensor (mean difference between SIR and SN rate: ACC vs. SN, MV vs. SN, DS vs. SN, respectively, 34.84, 17.60, 16.15 beats/min), though no sensors could mimic sinus rates under the default settings for sensor response factor (ACC vs. SN P-adjusted < 0.001; MV vs. SN P-adjusted = 0.002; DS vs. SN P-adjusted = 0.005). However, both in the range of 1 st minute and first 3 minutes of exercise, only the DS SIR profile did not differ from sinus rates (P-adjusted = 0.09, 0.90, respectively).

CONCLUSIONSThe DS under default settings provides more physiological rate response during physical activity than the corresponding single sensors (ACC or MV sensor). Further study is needed to determine if individual optimization would further improve adaptive performance of the DS.

Adult ; Aged ; Cardiac Pacing, Artificial ; methods ; Exercise ; physiology ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Pacemaker, Artificial

Objective:To investigate the short-term clinical efficacy of laparo-gastroscopic esophagectomy (LGE).Methods:The retrospective and descriptive study was conducted. The clini-copathological data of 11 patients with esophageal cancer who underwent LGE in the Zhongshan Hospital of Fudan University from June 2020 to October 2021 were collected. There were 8 males and 3 females, aged (68±4)years. Sorted by operation time, the sentinel lymph nodes navigation (SLN) was performed since the sixth patient in the cohort, and abdominal surgery and neck surgery were performed simultaneously to complete LGE. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect death of patients during postoperative 30 days. Patients were followed up during postoperative 30 days. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers. Results:(1) Surgical situations. Of the 11 patients, 5 cases received SLN with satisfactory visualization, 6 cases did not receive SLN, 1 case terminated the operation as sentinel lymph nodes biopsy showing positive results and the rest of 10 cases completed LGE successfully without conversion to thoracotomy. The operation time and tumor diameter of the 10 patients completing LGE was (204±27)minutes and (2.5±1.0)cm, respec-tively. (2) Postoperative situations. Of the 10 patients completing LGE, 2 cases had pulmonary complications after surgery and recovered well with symptomatic treatment, and none of patient had anastomotic leakage or other serious complication. Results of postoperative histopathological examination showed squamous cell carcinoma in the 10 patients completing LGE. Nine patients were classified as T1b?3N0M0 stage and 1 patient was classified as T1bN1M0 stage. Ten patients completing LGE had R 0 resection and the number of lymph nodes dissected was 14±4. There were 3 cases with nerve bundle invasion, 2 cases with vascular invasion and 5 cases without nerve bundle and vascular invasion. The postoperative treatment time at intensive care unit and duration of hospital stay of the 10 patients completing LGE were (4.0±2.4)days and (7.2±1.5)days. (3) Follow-up. The 10 patients completing LGE were followed up and none of them died during the postoperative 30 days. Conclusions:LGE is safe and feasible. Combined with SLN can guarantee the oncology effect of surgery.

Objective:To evaluate the clinical efficacy of omalizumab in the treatment of patients with chronic spontaneous urticaria accompanied by other allergic diseases.Methods:Clinical data were retrospectively collected from 74 patients, who were clinically diagnosed with chronic spontaneous urticaria and other allergic diseases, and received subcutaneous injections of omalizumab in the Department of Allergy, Tianjin Medical University General Hospital from June 2020 to September 2022. Types of allergic diseases, serum total IgE (tIgE) and allergen-specific IgE (sIgE) levels before treatment, treatment outcomes and adverse drug reactions were analyzed. Differences before and after treatment were assessed using paired t-test and Wilcoxon signed-rank sum test. Results:A total of 74 patients with chronic spontaneous urticaria were involved, including 29 with complicated allergic asthma (39.2%) , 61 with complicated allergic rhinitis (82.4%) , 6 with complicated atopic dermatitis (8.1%) , and 4 with food allergy (5.4%) . Before treatment, elevated serum tIgE or sIgE levels were observed in 44 (59.5%) patients. After the first omalizumab treatment, the urticaria control test (UCT) score significantly increased compared with that before treatment (16.00 [13.0.0, 16.00] vs. 6.00 [5.75, 9.00], Z = 7.39, P < 0.001) ; after 4 sessions of the omalizumab treatment, 82.5% (33/40) of the patients achieved complete control of urticaria symptoms or showed complete response. After omalizumab treatment, asthmatic attacks were decreased in 29 patients with allergic asthma, and asthma control test (ACT) scores significantly increased compared with those before treatment (21.07 ± 2.88 points [after the first treatment] vs. 18.48 ± 3.20 points [before treatment], t = 8.87, P < 0.001) ; among 61 patients with allergic rhinitis, global rhinitis symptom-based visual analog scale (VAS) scores (before treatment: 5.89 ± 1.29 points; after the first treatment: 3.28 ±1.46 points) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores (before treatment: 60.10 ± 20.53 points; after the first treatment: 37.26 ± 18.83 points) both significantly decreased after the first treatment ( t = 15.04, 10.01, respectively, both P < 0.001) , and rhinitis symptoms were relieved at the same time; skin itching was relieved in 4 patients with atopic dermatitis, and allergic symptoms after contact with food allergens were also relieved in the 2 patients with food allergy after omalizumab treatment. During the treatment, only 1 patient experienced erythematous swelling, induration, and pain at the injection site. Conclusions:In the treatment of chronic spontaneous urticaria accompanied by allergic diseases, the use of omalizumab not only effectively improved urticaria symptoms, but also well controlled allergic diseases, with a good safety profile. Multiple benefits may be achieved by the use of omalizumabin in patients with chronic spontaneous urticaria accompanied by other allergic diseases.

OBJECTIVETyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers. The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal, esophagogastric junction and gastric cancers, and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors.

METHODSIn this study, 180 tumor samples with histologically confirmed esophageal cancer (39 cases), cancer of the esophagogastric junction (92 cases) and gastric cancer (49 cases) were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by real-time PCR-optimized oligonucleotide probe method. EGFR protein expression was evaluated by immunohistochemistry (IHC) in 89 tumor samples.

RESULTSThe mutation analysis for EGFR (exons 18-21) showed no mutations in any of the hotspots of the gene in the 180 tumor samples analyzed. EGFR expression was negative in 12 tumor samples, 1+ in 31 tumor samples, 2+ in 24 tumor samples, and 3+ in 22 tumor samples. EGFR expression was 2+ or 3+ in 12 (92.3%) of the 13 esophageal squamous cell carcinomas, 29 (47.5%) of the 61 esophagogastric junction cancers, and 5 (33.3%) of the 15 gastric adenocarcinomas.

CONCLUSIONSOur results indicate that EGFR mutation in exons 18-21 is absent in the examined samples of esophageal, esophagogastric junction and gastric cancers. More studies are warranted to explore the predictive biological markers for the therapeutic response to EGFR TKI.

Adenocarcinoma ; genetics ; metabolism ; Adult ; Aged ; Carcinoma, Adenosquamous ; genetics ; metabolism ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Esophageal Neoplasms ; genetics ; metabolism ; Esophagogastric Junction ; metabolism ; pathology ; Exons ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; Young Adult

Background:There is no specific therapy for inflammatory bowel disease(IBD),and the pathogenesis of IBD is not fully clear. Aims:To explore the expression and clinical significance of IL-17BR in colon mucosa and peripheral blood mononuclear cell(PBMC)of patients with IBD. Methods:Colon mucosal biopsy specimens of 40 Crohn's disease(CD) patients,32 ulcerative colitis(UC)patients and 25 healthy controls and PBMC of 30 CD patients,27 UC patients and 25 healthy controls were collected. The expressions of IL-17BR in colon mucosa and PBMC were determined by immunohistochemistry and flow cytometry,respectively,and correlations between IL-17BR expression and levels of CRP, ESR,CDAI score and Mayo score were analyzed. Serum levels of TNF-α before and after infliximab(IFX)treatment were determined by ELISA,and correlations with IL-17BR were analyzed. Results:Compared with healthy controls,IL-17BR expressions in colon mucosa of CD and UC patients were significantly increased(P<0.05). IL-17BR expressions were significantly higher in active CD and UC patients than in remission CD and UC patients(P <0.05). No significant differences in IL-17BR expression in PBMC were found among CD,UC patients and healthy controls(P>0.05). The expression of IL-17BR in colon mucosa was positively correlated with CRP,ESR,CDAI score or Mayo score in CD,UC patients(P <0.05). After treatment with IFX,expression of IL-17BR in colon mucosa and serum TNF-α level were significantly decreased in CD patients(P<0.01). Expression of IL-17BR was positively correlated with serum TNF-α level in CD patients(P<0.05). Conclusions:The increasing of IL-17BR expression in IBD patients is closely correlated with activity of inflammation and TNF-α level. IL-17BR may play a vital role in immune response of intestinal mucosa,and can be used as a new marker for reflecting the activity of IBD.

A 59-year-old male patient presented with recurrent erythema and wheals all over the body for 6 years,complicated by irregular fever (the highest body temperature ＜ 39 ℃)and arthralgia for 2 months.He experienced a weight loss of 5 kg during two years prior to the presentation.Physical examination showed anemic comlexion,and there was no palpable enlargement of superficial lymph nodes,liver and spleen.Generalized erythema and wheals occurred all over the body,involving about 50％ of the body surface area.Histopathological examination of skin lesions showed infiltration of multiple neutrophilic granulocytes around blood vessels in the superficial dermis,and no vasculopathy was observed.Laboratory examinations revealed increased white blood cell (WBC) counts(13.97 × 109/L),erythrocyte sedimentation rate (ESR,136 mm/1 h) and C-reactive protein (CRP) level (75 mg/L),decreased hemoglobin level (96 g/L),and high serum levels of IgE (1 596 kU/L),IgG(20.4 g/L)and IgM(6 310 mg/L).Serum immunoelectrophoresis demonstrated that the IgM was a κ-type monoclonal immunoglobulin.Bone marrow examination showed active bone marrow hyperplasia.DNA sequencing analysis of 10 pairs of exons of the NLRP3 gene revealed 3 synonymous mutations,including c.663:C ＞ T:p.T221,c.732:G ＞ A:p.A244A and c.786:A ＞ G:p.R262R.Finally,the patient was diagnosed with Schnitzler's syndrome.There was no improvement of symptoms after the treatment with multiple oral antihistamines at increased dose levels.Then,the treatment protocol was adjusted to oral ciclosporin at a dosage of 200 mg/d for consecutive 18 days,but the patient still showed no response.After the treatment with oral prednisone (30 mg/d) and Tripterygium wilfordii tablets (66 μg thrice a day) for 2 weeks,the skin rashes subsided gradually,and arthralgia was relieved.Moreover,the WBC count,ESR and CRP level were decreased to 9.01 × 109/L,50 mm/1 h and 6 mg/L respectively,while the hemoglobin level was increased to 109.7 g/L.After 1-year follow-up,the dosage of glucocorticoids was gradually decreased to 8 mg/d.In addition,his condition was controlled well with no skin lesions and fever,except for occasional arthralgia in the knees and hip.