Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Objective:To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC).Methods:Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period.Results:Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression ( HR=2.87,95% CI:0.92~8.91, P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others ( HR=8.61,95% CI:1.38~53.73, P=0.021). Conclusion:SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

Objective: To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Methods: Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. Results: A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.

Objective:To evaluate the application of computer-assisted design and three-dimensional printing technique in reconstruction of maxillary defects with individual free fibular flap.Methods:A total of 13 patients, 7 males and 6 females with age from 12 to 55 years old, underwent the reconstruction of maxillary defects after subtotal or total maxillectomy for benign or malignant tumors between January 2016 and December 2018 were reviewed. Ther were 4 cases of subtotal maxillectomy and 9 cases of total maxillectomy. Before operation, osteotomy line was planned on three-dimensional images. A three-dimensional individual resin fibula model based on mirror images of the healthy side maxilla was obtained to fabricate an anatomically adapted osteomyocutaneous fibula free flap using computer-assisted design and forming. Oral, nasal, and eye functions and facial appearance were evaluated.Results:The 13 cases were followed up for 5-40 months, all flaps were alive except one due to flap failure and all cases were tumor free confirmed by CT or MRI. Ten patients could eat normal food without nasal food return, and 3 cases had palatal fistula. Eleven cases showed good speaking functional results. All cases had normal eye positions, no cases with diplopia and loss of vision. With evaluation by VAS, an average score of 8 was obtained, and most of patients were satisfied with their postoperative facial appearances.Conclusion:Reconstruction of maxillary defects by free fibular flap designed by three-dimensional printing and computer-assisted technique not only restored oral, nasal and eye functions, but also showed satisfactory facial appearance.

Objective:To explore the method of functional protection in transoral endoscopic thyroidectomy by vestibular approach.Methods:Retrospective analysis was performed on the case data of 66 patients who underwent transoral endoscopic thyroidectomy by vestibular approach in the Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital from February 2018 to February 2020. There were 11 males and 55 females aged 22-64 years, including 19 patients with benign diseases and 47 patients with malignant diseases. Important neurological functions were protected by a combination of anatomical exposure and intraoperative nerve monitoring. The clinical data and the effect of neurofunctional protection were summarized. SPSS 25.0 software was used for statistical analysis.Results:All operations were successfully completed with none transferred to open surgery. Three weeks after surgery, the numbness and tingling symptoms in the lower jaw and lower lip were basically relieved. There was no permanent mental nerve palsy, no permanent recurrent laryngeal nerve palsy but 2 cases with temporary recurrent laryngeal nerve palsy, no external branch injury of superior laryngeal nerve. There were 3 cases of temporary parathyroid gland dysfunction, 1 case of neck infection, 2 cases of subcutaneous effusion, 1 case of neck skin injury, and 2 cases of postoperative eye conjunctivitis.Conclusion:In transoral endoscopic thyroidectomy by vestibular approach, anatomical exposure can decrease mental nerve injury, and anatomical exposure combined with intraoperative nerve monitoring can protect the functions of the external branches of the superior laryngeal nerve and the recurrent laryngeal nerve.

Objective:To evaluate clinical applications and efficacy of submental artery perforator flap in reconstruction surgery after removal of pharyngeal carcinoma.Methods:A total of 27 patients in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University were included, 23 males and 4 females with age from 40 to 70 years old, and 17 patients were hypopharyngeal carcinoma (HPC) and 10 patients were oropharyngeal carcinoma (OPC). All patients underwent tumor resection followed by simultaneously reconstruction surgery using submental artery perforator flap between January 2015 and December 2019. Of 5 patients with palatine tonsil cancer, 4 underwent the combined approach of neck and oral resection and 1 with madibulotomy. All 5 patients with tongue base cancer received transhyoid partial glossotomy with or without partial laryngectomy. Sixteen patients with pyriform sinus carcinoma received partial laryngo-pharyngectomy with preservation of laryngeal functions. One patient with posterior hypopharyngeal wall carcinoma had partial pharyngectomy. Prognosis and laryngeal functions were analyzed after reconstruction surgery with submental artery perforator flap in patients with pharyngeal carcinoma.Results:The 27 patients were followed up for 6-66 months, with a median of 13 months, of them 24 patients were alive without recurrence or metastasis, 1 patient died of recurrence, 1 patient died of esophageal carcinoma and 1 patient was alive with the recurrence of tongue base carcinoma. Postoperative complications included flap failure for 1 case, pharyngeal fistula for 1 case, subcutaneous hydrops for 2 cases and lymphatic fistula for 1 case. Total 2 and 3 year survival rates were 92.9% and 88.9%, respectively. Total decanulation rate was 92.6%; decanulation rate and intubation time were 16/17 and 3.5 months in HPC patients; and decanulation rate and intubation time were 9/10 and 2 months in OPC patients. Total oral feeding rate was 92.6% and nasogastric feeding time was 3.5 weeks in HPC patients and 3 weeks in OPC patients.Conclusion:The submental artery perforator flap is an excellent choice for reconstruction surgery after removal of oropharyngeal and hypopharyngeal carcinoma, with good outcomes of laryngeal functions.

Objective:To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma.Methods:Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ 2) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results:A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy ( P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion:TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.

Objective: To investigate the correlation between the expression of E2F1 and growth arrest and DNA damage inducible protein 45g (GADD45g) in patients with acute myeloid leukemia (AML), and to explore whether GADD45g exerts its induction of DNA damage, cell apoptosis, senescence, cell cycle arrest and drug sensitivity in AML through inhibition of E2F1. Methods: A total of 32 cases of bone marrow specimens from patients initially diagnosed asAML in Hospital of Blood DiseasesAffiliated to ChineseAcademy of Medical Sciences from January 2013 to December 2016, were selected for this study; In addition, AML cell lines (U937, HL60, THP-1, Molm-13) were also collected for this study. The mRNAexpression of GADD45g and E2F1 in above mentioned specimens and cell lines by qPCR,andtheircorrelationwasalsoanalyzed.Thelentiviral vector over-expressing E2F1 (pLV-E2F1-RFP) was constructed to prepare recombinant lentivirus, which was then transfected Molm-13 and THP-1 cells that over-expressing GADD45g. Whether GADD45g exerts tumor inhibition effect on AML cells through inhibition of E2F1 was determined by comet assay, Annexin V/7AAD flow cytometry, β-galactosidase staining and PI staining flow cytometry etc. Results: The mRNA expression of GADD45g was negatively correlated with E2F1 in bone marrow of AML patients and AML cell lines (r=–0.663, P<0.01). Over-expression of GADD45g significantly inhibited the expression of E2F1 in AML cell lines (all P<0.01). Molm-13 and THP-1 cells that simultaneously over-expressing GADD45g and E2F1 were successfully constructed. Compared with the control group, the protein expressions of GADD45g and E2F1 in over-expression groups were significantly increased (all P<0.01). Compared with cells over-expressing GADD45g alone, simultaneous over-expression of both GADD45g and E2F1 significantly reduced the apoptosis, senescence and DNA damage (all P< 0.01), and rescued cell cycle arrest in Molm-13 and THP-1 cells (all P<0.01), thus further reduced the chemo-sensitivity of AML cells caused by GADD45g over-expression (all P<0.01). Conclusion: GADD45g exerts anti-tumor effect inAMLvia inhibition of E2F1.

Objective To analyze the overactive bladder symptom score (OABSS) in evaluating bladder dysfunction in the different stages among type 2 diabetes mellitus patients,and to explore the value of bladder hyperactivity symptom score in screening early diabetic bladder dysfunction.Methods A total of 1 157 patients with type 2 diabetes mellitus,aged 40-88 yearswith mean age of 60.2 years,were enrolled from October 2013 to October 2016.The survey included the patients' characteristics,past history,current history,OABSS and quality of life (QOL) index scores.T test,single factor analysis of variance and multiple regression analysis are used to analyze the results.Results As many as 1 157 were qualified for final statistical analysis.OABSS is 1.94 ± 1.23 in group with diabetes duration ＜ 10 years,3.24 ± 1.45in group with diabetes duration 10-20 years,and 4.00 ± 1.72 in group with diabetes duration ＞ 20 years.The differences of OABSS in the different duration of diabetes was statistically significant.As diabetic duration increased,OABSS value increased (F =48.419,P ＜ 0.001).The difference of OABSS in the different HbA1c level,age and concurrent peripheral neuropathy was statistically significant.There was no significant difference of OABSS in the different BMI and distinct therapies.There was no significant difference of OABSS in diabetes with hypertension and without hypertension,with cardiopathy and without cardiopathy,with cerebrovascular disease (CVD) and without CVD,with hyperhpemia and without hyperlipemia.The significant factors were used to make multivariate analysis.The results showed that the duration of diabetes,HbA1 c level,age,peripheral neuropathy were still statistically significant.Standardized partial regression coefficient of diabetic duration was 0.366.OABSS was positively correlated with QOL score (r =0.434,P ＜ 0.001).Conclusions The related symptoms in OABSS with diabetic bladder dysfunction is correlated with the duration of diabetes,HbA1c level,age,concurrent peripheral neuropathy among type 2 diabetes.The duration of diabetes was the most significant factor.OABSS is likely to be one of the tools to assess the early symptoms of diabetic bladder dysfunction.

Lesch-Nyhan syndrome(LNS) is a congenital X-linked recessive inherited disorder caused by mutations in the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene.A deficiency of the HPRT enzyme is responsible for the disease.The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis and neurological developmental disorders.Studies have reported there are more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low.Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth.DNA of patient and his family members were extracted from peripheral blood lymphocytes.The coding region and the intron-exon boundaries of HPRT gene were sequenced by standard methods.We found a mutation in exon 3 of the HPRT gene of the patient and his mother (Exon3:c.143G>A), which resulted in an arginine to histidine (p.R48H) substitution in the encoded protein.No activity of the enzyme HPRT was detected in the erythrocytes.The same mutation was reported in several European families, but was found in Chinese family for the first time.Clinicians in China have poor experience in diagnosing LNS case, due to the low incidence in China.Therefore LNS screening for infants or adolescents with hyperuricemia, gouty arthritis and neurological dysfunction should be performed.