Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To analyse the safety and feasibility of laparoscopic techniques in the treatment of elderly patients with acute intestinal obstruction.Methods A prospective two-center single-arm clinical study was conducted.A total of 441 patients with acute intestinal obstruction treated at the department of general surgery of Longyou County People's Hospital and Hospital Affiliated to Qinghai University from October 2017 to October 2021 and met the inclusion criteria were selected as study subjects.Among them,10 patients had chronic obstructive pulmonary disease(COPD)and were given mechanical ventilation,noninvasive ventilation,continuous low-flow oxygen inhalation,nebulization inhalation,and bronchodilator treatment after surgery.Twelve patients had chronic kidney disease(CKD)and were given hemodialysis treatment after surgery.All 441 patients underwent laparoscopic exploration,small intestine decompression,and definitive surgery.After surgery,they received intravenous nutrition,antibiotics,and subcutaneous injection of low-molecular-weight heparin(10 U/kg).The blood gas analysis(for patients with COPD),renal function(for patients with CKD),weight,body mass index(BMI),complications,and prognosis were observed before surgery,after surgery,and at discharge.Results There were 441 elderly patients with intestinal obstruction in the study,including 240 males and 201 females.The mean duration of the disease was(74.2±6.4)hours,and the BMI was(25.4±6.7)kg/m2.A total of 280 patients with adhesions underwent adhesion lysis surgery,while 87 patients with small bowel necrosis and 19 patients with small bowel lipoangiomatosis underwent small bowel resection and anastomosis.Additionally,21 patients with obturator hernia underwent hernia repair surgery,and 34 patients with small bowel persimmon stones underwent small bowel incision and stone removal surgery.For the 10 patients with COPD,there was a significant increase in arterial partial pressure of oxygen[PaO2 mmHg(1 mmHg≈0.133 kPa):80.3±3.3 vs.72.6±2.7,P<0.01],and a significant decrease in arterial partial pressure of carbon dioxide(PaCO2)compared to preoperative levels(mmHg:35.7±3.6 vs.47.6±1.3,P<0.01).Four patients died of type Ⅱ respiratory failure,and 6 patients had a significant decrease in PaO2[(77.4±6.7)mmHg]and a significant increase in PaCO2[(42.1±5.2)mmHg]at discharge compared to postoperative levels(both P<0.01).Among the 12 patients with CKD,both blood urea nitrogen(BUN)and serum creatinine(SCr)increased significantly after surgery compared to preoperative levels[BUN(μmol/L):79.5±8.5 vs.18.8±4.7,SCr(μmol/L):312.7±12.1 vs.138.4±9.7,both P<0.01].Two patients died of renal failure,and 8 patients had a significant decrease in BUN[(9.2±0.7)μmol/L]and SCr[(112.5±3.8)μmol/L]at discharge compared to postoperative levels(both P<0.01).There were no significant differences in BMI and weight between preoperative,postoperative,and discharge times[BMI(kg/m2):25.4±6.7,24.9±3.9 vs.23.9±3.5;weight(kg):74.2±6.8,73.7±3.3 vs.72.8±4.6;all P>0.05].A total of 435 patients recovered from acute intestinal obstruction with no complications such as lower extremity venous thrombosis,intestinal fistula,wound dehiscence,or wound infection.Conclusion The strategy of treating elderly patients with acute intestinal obstruction by laparoscopic exploration,intestinal decompression,definitive surgery,treatment of underlying diseases,and subcutaneous injection of low-molecular-weight heparin is safe and feasible.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

Cholangiocarcinoma is a malignant tumor of the biliary tract with high heterogeneity and poor prognosis. Surgery is the only cure for early cholangiocarcinoma, but about two thirds of the patients are already advanced at the time of initial diagnosis. First-line chemotherapy in patients with advanced cholangiocarcinoma does not lead to viable survival. In recent years, with the development of second-generation sequencing technology, potential targets in cholangiocarcinoma have been continuously discovered, and a series of clinical trials have been carried out accordingly. Among them, clinical trials of drugs targeting fibroblast growth factor receptors (FGFRs) have yielded promising results. This article reviews the current status and research progress of drugs targeting FGFRs in the treatment of advanced cholangiocarcinoma.

Objective:To investigate the role of LncRNA ZBED3-AS1 in osteoblast proliferation and differentiation in osteoporotic rats through regulating miR-339-5p/Notch 1.Methods:The rat models of sham operation (Sham) group and model (Model) group were established, and the bone mineral density (BMD) of rats was examined. Rat osteoblasts were isolated and the expression of ZBED3-AS1 and miR-339-5p was detected by qRT-PCR. The osteoblasts of rats in Sham group and Model group were divided into different groups and transfected. CCK8, alizarin red (AR-S) staining and alkaline phosphatase (ALP) staining were used to detect the proliferation and differentiation ability of cells in each group. The distribution of ZBED3-AS1 in cells was determined by FISH assay. Double luciferase report confirmed the relationship between ZBED3-AS1 and miR-339-5p as well as miR-339-5p and Notch 1.Western blot was used to detect the expression of Notch pathway related factors.Results:The bone mineral density of femur in Model group was significantly lower than that in Sham group ( P=0.0057) . Compared with Sham group, the expression of ZBED3-AS1 in osteoblasts of Model group was lower, while that of miR-339-5p was higher (all P<0.05) . Overexpression of ZBED3-AS1 could promote the proliferation and differentiation of osteoblasts, while knockdown of ZBED3-AS1 could inhibit the proliferation and differentiation of osteoblasts (all P<0.05) . ZBED3-AS1 could regulate miR-339-5p as ceRNA (all P<0.05) . Overexpression of miR-339-5p can inhibit the proliferation and differentiation of osteoblasts, which can be partially saved by overexpression of ZBED3-AS1. Notch 1 was confirmed as a target of miR-339-5p, at the same time, interfering with the expression of ZBED3-AS1/miR-339-5p can affect the expression of Notch-1 protein, and the regulation of ZBED3-AS1/miR-339-5p on osteoblasts may be realized through Notch pathway. Conclusion:ZBED3-AS1 can be used as ceRNA to regulate miR-339-5p, and then affect the proliferation and differentiation of osteoblasts in osteoporotic rats.

Objective:To study the effects of hypertensive disorders of pregnancy (HDP) on the birth weight (BW) differences in twins.Method:From January 2011 to January 2020, twins delivered in our hospital were retrospectively analyzed. The twins born to HDP mothers were the HDP group and those born to healthy mothers were the control group. The maternal and neonatal data of the two groups were collected and the effects of HDP on the BW differences were analyzed.Result:The age of the mothers, the proportion of mothers of older ages and more-than-once delivery in HDP group (418 cases) were significantly higher than the control group (499 cases) [(31.4±5.3) years vs. (30.4±3.8) years, 26.6% (111/418) vs. 12.6% (63/499), 20.6% (86/418) vs. (15.0% (75/499)] ( P<0.05). The gestational age (GA) of newborns in the HDP group (836 cases) was significantly lower than the control group (998 cases) [(35.1±2.2) weeks vs. (36.7±1.2)]( P<0.05). The proportion of twins with GA <34 weeks in the HDP groups was significantly higher than the control group [24.2% (101/418) vs. 3.8% (19/499)] ( P<0.05). Cesarean section was the main delivery mode in both groups. The BW differences of the twins in the HDP group were larger than the control group [22.4% (9.1%, 31.9%) vs. 13.1% (5.8%, 19.6%)]. Significantly more twins in the HDP group showed ≥30% BW difference than the control group [28.7% (120/418) vs. 3.8% (19/499)] ( P<0.05). The incidences of BW discordant in twins (BWDT) in the HDP group was significantly higher than the control group [BWDT≥15%:61.5% (257/418) vs. 38.3% (191/499), BWDT≥20%: 51.4% (215/418) vs. 25.3% (126/499)] ( P<0.05).Among twins with GA of 34~37 weeks, the BW of the bigger infants and the smaller infants in the HDP group were all lower than the control group and the percentage of BW difference was significantly higher than the control group ( P<0.05). Conclusion:HDP may influence the intrauterine growth of the twins, aggravate the BW differences and increase the incidences of BWDT. It is necessary to make better prenatal management of HDP and closely monitor the intrauterine growth of the fetuses.

ObjectiveTo establish a hospice care training system for nurses in general hospitals and evaluate its implementation effects, and to explore a new path for hospice care education. MethodsThe nurses from 7 clinical departments in the First Affiliated Hospital of He＇nan University of Chinese Medicine from September 2017 to June 2018 were selected by convenience sampling with 24 nurses from each department and randomly divided into the general training group (12 for every department) and in-depth training group (12 for every department). Based on the classic education theory, the nurse hospice care training system for general hospital was established from five aspects including goal, content, method, management and teachers in the in-depth training group and the general training group received the training according to hospice care nursing plan implementation rules of the First Affiliated Hospital of He＇nan University of Chinese Medicine. The two groups were compared in terms of the training effects. ResultsAfter training, in the in-depth training group, the scores of theoretical assessment and skill assessment of hospice care of nurses in the 7 departments were all higher than those in general training group, and the differences were statistically significant (P＜ 0.05). ConclusionsThe general hospital nurse hospice care training system can effectively improve the employees＇knowledge reserve and skills level of hospice care; the strengthening of the construction of hospice care training system is important to guarantee the qualified hospice care nursing team building and to improve the quality of hospice care services.

Objective To compare the efficacy of night type brace and Boston brace for the treatment of adolescent idiopathic scoliosis. Methods 60 patients with AIS were randomized into two groups,night type brace group and Boston brace group ,30 patients respectively. Patients were treated with night-time brace in night type brace group ,while patients were treated with brace all day long in Boston brace group. The patients were followed up every 3 months. The spinal anteroposterior and lateral position films and relevant indexes were eval-uated. Results There were significant statistical differences between the two groups on main thoracic Cobb angle improvement,ICR and IAV. The night type brace was superior to the Boston group. However,there were no signifi-cant differences between the two groups on lumbar Cobb angle improvement,T4-T12 kyphosis and L1-S1 lordosis. Conclusion The night type brace is superior to the Boston brace for the treatment of adolescent idiopathic scoliosis.

Objective To investigate the expression and significance of epithelial cell adhesion molecule (Ep-CAM) in breast cancer.Methods Twenty-three cases of breast cancer tissue samples and paired lymph node metastases confirmed pathologically were collected.Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics technology was used to screen and identify the differentially expressed proteins between primary tumor and lymph node metastasis of breast cancer.The expression of Ep-CAM was detected by Western blotting in 4 cases of primary breast cancer tissues and paired lymph node metastases.And the expressions of Ep-CAM in 252 cases of breast lesions were detected by immunohistochemical method.Results Quantitative proteomic examination results showed that differentially expressed proteins existed in breast cancer primary tumor and lymph node metastasis,and the expression of Ep-CAM in metastatic lesions was higher than that in primary tumor.Western blotting results showed that the expression of Ep-CAM in metastatic lesions (1.46 ± 0.22) was higher than that in primary tumor (1.16 ± 0.09),which was consistent with the results of proteomic.The immunohistochemical results showed that the positive expression rate of Ep-CAM in lymph node metastasis tissues (93.16％,109/117) was significantly higher than that in primary breast cancer without metastasis (72.73％,64/88),and the difference was statistically significant (x2 =15.921,P =0.000).The positive expression rate of Ep-CAM in primary breast cancer with lymphatic metastasis (72.65％,85/117) was lower than that in paired lymph node metastases (P =0.001).Conclusion Ep-CAM is differentially expressed in primary tumor and lymph node metastasis of breast cancer,which may be related to the lymphatic metastasis of breast cancer.