Objective:To investigate the feasibility, safety and effectiveness of colonic interposition with vascular anastomosis in reconstructing the entire esophagus and hypopharynx after resection of hypopharyngeal cancer with esophageal cancer.Methods:We conducted a retrospective analysis of 4 male patients with simultaneous multiple primary cancers of the hypopharynx and esophagus, aged 47 to 58, treated in the Department of Head and Neck Surgery at the Hunan Cancer Hospital from February to August 2019. All cases underwent total hypopharyngectomy and total esophagectomy, of whom, three cases presented with total laryngectomy and one case with larynx preservation. Colonic interposition was performed using the left colic artery as a pedicle, with an average colonic length of 48.5 cm. The colon was elevated through the esophageal bed to the neck, and the branch of the colonic mesenteric artery was anastomosed to one of the neck arteries, including the inferior thyroid artery in one case, the transverse cervical artery in two cases, and the superior thyroid artery in one case, and all venous anastomoses were performed with the internal jugular veins.Results:The postoperative neck and abdominal wounds healed well without anastomotic leakage, and all patients were able to resume a regular oral diet within 21-30 days postoperatively. During the follow-up of 48-52 months, two cases died due to tumor recurrence, while the remaining two cases were disease-free survivals.Conclusion:Colonic interposition with vascular anastomosis is a safe and reliable reconstruction method suitable for repairing long-segment upper digestive tract defects after resection of hypopharyngeal cancer with esophageal cancer.

Objective:To observe the projections from tyrosine hydroxylase(TH)positive neurons in locus coerule-us(LC)to tachykinin-1(TAC1)neurons in paraventricular nucleus of the thalamus(PVT),and morphologically determine whether they are involved in transmission and modulation of nociceptive information.Methods:TAC1-ires-Cre mice were hybridized with Rosa26:CAG-LSL-tdTomato(Ai9)mice.And spared nerve injury(SNI)induced neu-ropathic pain model was established with TAC1-ires-Cre::Ai9 mice to observe the colocalization of TAC1 and Fos and the close appositions between TAC1/FOS double-labeled neurons and TH positive axonal terminals.The distribution of the TH positive neurons and FG retrogradely labeled neurons were observed in the LC after Fluorogold(FG)was injec-ted into the PVT.Finally,the coexistences of TH positive neurons and RV labeled neurons in the LC were observed after injection of RV-mediated retrograde tracing system.Results:TAC1 positive neurons were shown with red fluores-cence in TAC1-ires-Cre::Ai9 mice.TAC1/FOS double-labeled neurons were found in the PVT of the SNI model.Some TAC1/FOS double labeled neurons made close appositions with TH positive axonal terminals.FG retrogradely labeled neurons were observed in the LC after FG injected into the PVT,and some of the FG labeled neurons coexisted with TH positive neurons.Using RV retrograde transsynaptic tracing virus,the results showed that presynaptic neurons of TAC1 positive neurons in the PVT were found in the LC,and most of the presynaptic neurons were TH positive neu-rons.Conclusion:TH positive neurons in the LC project to TAC1 positive neurons of the PVT,forming LCTH+-PVTTAC1+neural circuit,which were activated by nociceptive information.It demonstrates that this pathway plays a role in pain transmission or regulation.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Osteosclerosis is a rare hereditary bone metabolic disease, characterized by increased bone mass and density caused by bone resorption disorders, and any abnormal mutation involving osteoclast maturation or function will lead to the occurrence of osteopetrosis. Clinically, the prevalence of autosomal dominant osteopetrosis type Ⅱ(ADO-Ⅱ) is higher than that of other types of osteopetrosis, which involves multiple systems such as endocrine, bone, blood, nerve, ear-nose-throat, and oral cavity. Disease progression is insidious and easily overlooked, and there is no standard treatment. This article summarizes the clinical characteristics, examination data, diagnosis and treatment process of the two patients, analyzes multi-system symptoms, pathogenesis and treatment principles of the disease to improve the management of patients with ADO-Ⅱ.

Tight junction(TJ) is complex dynamic system involved in protein interactions in the paracellular secretory pathway, with both barrier and fence functions. Claudin family, the main section of tight junction strands, will be abnormal in expression pattern in the circumstances of radiation injuries, inflammation, Sj?gren's syndrome, diabetes and other pathological conditions in salivary glands. This change leads to abnormal structure and function of tight junctions, indirectly manifested as salivary gland dysfunction. In addition, the difference of Claudin expression in salivary gland tumors can also be used as an indicator of tumor type and prognosis. This review focuses on the progress of research on common Claudin in salivary glands, including the structure, function, expression patterns of related diseases and their applications. It is believed that the review may provide new ideas for clinical and basic research on Claudin protein-related diseases.

Objective:To optimize the different salt preparation processes of salt-processed Psoraleae Fructus and compare the differences among different salt products.Methods:Ultra-high performance liquid chromatography (UPLC) characteristic chromatogram of Psoraleae Fructus was established. By using the comprehensive scoring method, the total content of psoralen and isopsoralen and the peak area of the characteristic chromatogram were used as the evaluation index to optimize the four different processing technologies, including "stir-frying with salt-water", "steaming with salt-water", "spraying with salt-water" and "microwaving with salt-water". Meanwhile, entropy weight TOPSIS method, clustering analysis (HCA), principal component analysis (PCA) and other chemical pattern recognition methods were used to compare the quality difference of different salt-processed Psoraleae Fructus.Results:The optimized "stir-frying with salt-water" process of salt-processed Psoralea Fructus was 170 ℃ for 13 min, "steaming with salt-water" process for 1 h, "spraying with salt-water" process for 110 ℃ for 13 min and "microwaving with salt-water" process for 105 s microwave heating. TOPSIS comprehensive evaluation results of entropy weight showed that the quality of different salt products of Psoraleae Fructus ranked as product of stir-frying with salt-water > product of stir-frying with green salt-water > product of spraying with salt-water > product of microwaving with salt-water > product of steaming with salt-water; HCA results showed that different salt products of Psoraleae Fructus could be polymerized into two categories, between which product of stir-frying with salt-water and product of stir-frying with green salt-water were polymerized into one category; product of spraying with salt-water, product of microwaving with salt-water and product of steaming with salt-water were another category; the results of PCA showed that different salt products of Psoraleae Fructus could be clustered into 4 categories, among which product of stir-frying with salt-water, product of stir-frying with green salt-water and product of spraying with salt-water were clustered into the same category respectively, and product of microwaving with salt-water and product of steaming with salt-water were clustered into the same category.Conclusion:The chemical composition of Psoraleae Fructus processed by different salting methods is different. The results of this study can provide reference for processing optimization of salt-processed Psoraleae Fructus and identification of different salt products.

Hereditary hemochromatosis(HH) is relatively rare in the Chinese population, and the disease can involve multiple systems. It is easy to be missed and misdiagnosed due to nonspecific clinical manifestations. We report on a case with diabetes as the first diagnosis and being confirmed HH later. In addition to abnormal liver function, this patient also developed a variety of endocrine and metabolic diseases such as hypogonadism and osteoporosis. Included with this case report is a literature based discussion of clinical features, management of HH along with its relationship with endocrine dysfunction to improve disease understanding.

Objective:To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis.Methods:The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed.Results:（1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups ( P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different ( P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups ( P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences ( P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant ( P<0.05). Conclusions:The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

Five patients with primary malignancies in the pterygopalatine fossa (PPF) and infra temporal fossa (ITF) were enrolled in this retrospective study between January 2012 and January 2018. After malignancies proven by biopsy and evaluation with CT and MRI scan, all patients received modified maxillary swing (MMS) approach for extirpation of malignant tumors in the PPF and ITF under general anesthesia. En bloc resection with wide surgical margins was successfully performed in all cases. Negative margins were observed in 4 cases and positive margins were found in one patient with adenoid cystic carcinoma who received postoperative radiotherapy. The most common complication was facial numbness. During the follow-up period (range 12 to 57 months), one patient suffered from recurrence while others did not. The advantages of MMS include wide surgical field, full exposure and easy manipulation. The MMS approach is expected to become an standard method for monobloc resection of malignancies in the PPF and ITF.

Objective To detect phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) protein expression in epithelial ovarian cancer and cell lines,and to examine the effects of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor AZD6244 on cell proliferation,apoptosis as well as cell cycle of ovarian cancer cells.To explore the function and significance of MAPK/extracellular signal-regulated kinase (ERK) signaling pathway in the development of ovarian cancer.Methods (1) A total of 104 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in First Affiliated Hospital,Dalian Medical University from January 2004 to December 2013 were selected.The expressions of p-ERK1/2 protein were detected by immunohistochemistry in ovarian cancer specimens,and the relationship between the expressions of p-ERK1/2 and the clinical features of patients was analyzed.(2) p-ERK1/2 and other related proteins were determined by western blot in various ovarian cancer cells,including SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3 treated with or without MEK inhibitor.The cellular proliferation,apoptosis and cell cycle of ovarian cancer cells after treatment with MEK inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry,respectively.Results (1) The immunohistochemical method showed that p-ERK1/2 between low grade serous carcinoma and clear cell carcinoma were not significantly higher expressed (P＞0.05).However,a lower level of the p-ERK1/2 expression were observed among high grade serous carcinoma,mucinous carcinoma and endometrioid carcinoma (all P＜0.05).There was no significant correlation between the protein expression of p-ERK1/2 and patients' age,pathological stage of surgery,and preoperative serum CA125 level (P＞0.05).(2) Western blot showed that the protein p-ERK1/2 was widely expressed in various ovarian cancer cell lines such as SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3.After treatment with AZD6244 (5,10 μmol/L),the level of p-ERK 1/2 in OVCAR5 and OVCAR8 decreased significantly in dose-dependent manner.Additionally,we found a reduction of the expression level of cyclin D 1,caspase-3 and appeared cleaved poly adenosine diphosphate ribose polymerase (PARP) in OVCAR5 and OVCAR8,compared with control groups.MTT assays showed that OVCAR5,OVCAR8 and A2780S were differently inhibited in the dose-dependent manner after being treated with different concentrations of AZD6244 (0,2.5,5,10,25,50 and 100 μmol/L,all P＜0.05).Further tested by flow cytometry,the results showed that AZD6244 (5,10 μmol/L) was able to induce the apoptosis of OVCAR5,OVCAR8 and A2780S,as well as G0/G1 phase arrest,both in a dose-dependent manner (P＜0.05).Conclusions As the main active and functional unit of MAPK/ERK signaling pathway,p-ERK1/2 protein is expressed in both the tissues and various ovarian cancer cell lines.AZD6244 could down-regulated the expression of p-ERK1/2 in ovarian cancer cells,accompanied by the decreased proliferation and increased cell apoptosis of ovarian cancer cells.In conclusion,MAPK/ERK signaling pathway might play a role in the development and progression of ovarian cancer,and may be provide a novel option for molecular targeted therapies of the disease.