Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Objective:To compare the safety and efficacy of high-dose- rate interstitial brachytherapy and particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases in the field after external radiotherapy.Methods:Clinical data of 42 patients with residual or newly metastatic pelvic lymph nodes after radiotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria from January 2017 to April 2020 were retrospectively analyzed. Among them, 12 patients were male and 30 females, aged 39-82 years, (61.6±9.64) years on average. According to the treatment method, all patients were divided into the high-dose-rate interstitial brachytherapy group ( n=18) and particle implantation radiotherapy group ( n=24). During 3-year follow-up, the local control rate (LCR), incidence of complications and overall survival (OS) were compared between two groups. Age and operation time conforming to normal distribution were analyzed by t-test. The remaining indexes were analyzed by the Chi-square test or Fisher's exact test. The OS and LCR were calculated by Kaplan-Meier method. Results:There was no significant difference in baseline data between two groups (all P>0.05). The operation time in the high-dose- rate interstitial brachytherapy group was longer than that in the particle implantation radiotherapy group [(66.39±11.07) : (45.75±9.19) min, P<0.001]. During subsequent follow-up, there was no significant difference in the LCR between two groups (1-year LCR 88.9% vs. 87.5%, P=0.927; 2-year LCR 72.2% vs. 62.5%, P=0.874). There was no significant difference in the median OS between two groups (31.6 vs. 29.8 months, P=0.798). There was no significant difference in the incidence of early complications between two groups [ (4/18) vs. 5/24 (20.8%), P=1.000]. No late complications observed. Conclusion:High-dose- rate interstitial brachytherapy yields equivalent efficacy and safety to particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases.

Objective:To analyze the prognosis and risk factors for brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete resection, aiming to identify those most likely to benefit from prophylactic cranial irradiation (PCI).Methods:Clinical data of 94 patients with LS-SCLC treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2005 to December 2018 who underwent complete resection were retrospectively analyzed, including 31 cases treated with PCI and 63 without PCI. Prognostic factors and risk factors of BM were analyzed by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Independent risk factors of overall survival (OS) and BM were assessed by multivariate Cox regression model.Results:The 2-year and 5-year OS rates were 80.6% and 61.3% in the PCI group, and 61.9% and 46.0% in the non-PCI group, respectively ( P=0.001). The 2-year and 5-year brain metastasis-free survival (BMFS) rates were 80.6% and 54.8% in the PCI group, and 57.1% and 42.9% in the non-PCI group, respectively ( P=0.045). The 2-year and 5-year progression-free survival (PFS) rates were 71.0% and 48.4% in the PCI group, and 49.2% and 34.9% in the non-PCI group, respectively ( P=0.016). PCI could improve OS in patients with pII/III stage LS-SCLC ( P=0.039, P=0.013), but the OS benefit in patients with pI stage LS-SCLC was not significant ( P=0.167). BM occurred in 3 patients (9.7%) in the PCI group, which was significantly lower than that in the non-PCI group ( n=17, 27.0%; P=0.044); there was no significant difference in the BM rate of patients with pI and pII stage LS-SCLC between PCI and non-PCI groups ( P=0.285, P=0.468); and the BM rate of patients with pIII stage LS-SCLC in the PCI group was significantly lower than that in the non-PCI group ( P=0.041). Multivariate analysis showed age ≥60 ( HR=2.803, P=0.001), BM ( HR=2.239, P=0.022), no PCI ( HR=0.341, P=0.004) and pathological stage pII/III ( HR=4.963, P=0.002) were the independent high-risk factors affecting OS; and pathological stage pII/III ( HR=11.665, P=0.007) was an independent high-risk factor affecting BM. Conclusions:LS-SCLC patients with pII-III stage have a higher risk of developing BM and poor prognosis after complete resection, and should receive PCI treatment. However, LS-SCLC patients with pI stage may not benefit significantly.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective:To preliminarily evaluate the safety and efficacy of 3D printing template-assisted brachytherapy in the treatment of solitary metastatic lymph nodes adjacent to iliac vessels.Methods:Clinical data of 12 cases of para-iliac lymph node metastasis after radiotherapy admitted to our hospital from October 2018 to April 2020 were retrospectively analyzed. All patients received 3D printing template-assisted brachytherapy at a prescription dose of 20-30 Gy/fraction. CT scan was reviewed every 1 month in the first 3 months after treatment and every 3 months at 3 months after treatment.Local control rate, symptom relief rate and adverse events were evaluated.Results:All the 12 patients successfully completed the treatment and follow-up. At 1, 3 and 6 months after 3D printing template-assisted brachytherapy, 2, 2 and 3 patients obtained complete remission of lymph nodes, 9, 8 and 8 cases of partial remission, 1 case of stable disease and no case of disease progression. The symptoms were relieved in 10 patients. Acute radiation enteritis occurred in 2 patients and myelosuppression in 2 patients, which were mitigated after symptomatic treatment.Conclusion:3D printing template-assisted brachytherapy may be an efficacious and safe treatment of para-iliac lymph node metastasis, which yields tolerable adverse events.

Objective To observe the functional connectivity of attentional network in first-episode treatment-naive depressed patients with resting-state functional MR imaging (rfMRI),and to investigate the neuropathologic mechanism of attention dysfunction.Methods Eighteen first-episode treatment-naive depressed patients were collected in our hospital from August 2015 to March 2017,and 16 healthy controls matched with age,gender and education were chosen at the same time period.All subjects accepted rfMRI.Pearson correlation analysis was performed on all the time series values of the two regions of interest (ROIs),and their correlation coefficient was obtained.Fisher z transformation was performed to reflect the functional connection strength of the two ROIs through z scores.Results As compared with healthy controls,depressed patients showed abnormal enhancement on functional connectivity of the attentional network in the left anterior cingulate and supplementary motor area (z scores:0.21 ±0.10 vs.0.13±0.09,P=0.029),right basal ganglia region and dorsolateral prefrontal cortex (z scores:0.18±0.12 vs.0.10±0.08,P=0.048),right frontal eye field and intraparietal suleus (z scores:0.19± 0.12 vs.0.10±0.05,P=0.006),right frontal eye field and nucleus ceruleus (z scores:0.18±0.13 vs.0.09± 0.07,P=0.018).Conclusion Abnormal functional connectivity of attentional network exists extensively in first-episode treatment-naive depressed patients,which may be due to attention impairment in depressed patients.

Objective To investigate the effect of exogenous vascular endothelial growth factor (VEGF) on bone activity of rabbit heterotopic allograft decalcified bone.Methods 140 adult healthy China white rabbits were selected,no limitation with sex,20 rabbits as the donor preparation of allogenic decalcified bone,according to the random number table,the rest was divided into the experimental group (allograft decalcified bone ± VEGF) and the control group (Allograft decalcified bone),each group contained 60 rabbits.For the experimental group,the prepared 1.5 cm long homologous decalcified tibia was placed in rabbit right thigh of rectus femoris and vastus medialis muscle gap near by saphenous artery,and fixed on the femur with two 0.8 mm Kirschner wire.In the vicinity of the skin,implanted an osmotic pump which contain the VEGF solution 200 μl with concentration was 0.5 μg/ml.In the control group,implanted the isometric allograft decalcified bone in rabbit right thigh corresponding parts with the same method.Each group respectively at 0,2,4,6,8,10 weeks to death 10 white rabbits,By specimen observation,HE dyeing observation and detection of type Ⅰ glue protein fluorescence intensity,Analysis the bone activation degree of two groups of bone allograft decalcified.Results Experimental allograft decalcified bone gradually wrapped by connective tissue membrane,its surface appear different size of the pits and gradually increased and become deep,while the control group pits relatively little and shallow.In the experimental group and control group,the fluorescence intensity of type Ⅰ collagen reached its peak respectively at 8 weeks (47.57 ±3.50) and 10 weeks (45.07±6.02),with no statistically significant (P ＞ 0.05).Conclusion Rabbit allograft decalcified bone implanted in the muscle clearance with abundant blood supply can be transformed into activated bone after 10 weeks,and after applying exogenous VEGF,allograft decalcified bone can be transformed into activated bone after 8 weeks,the bone activation process obviously speed up.The reaults confirmed the exogenous VEGF can obviously promote the ectopic rabbit bone allograft decalcified bone activation process.

Objective To evaluate the effects of impaired glucose tolerance (IGT) on ventricular remodeling. Methods Parameters of every subject including left ventricular mass ( LVM), left ventricular mass index (LVMI), E/A ratio, 75 g oral glucose tolerance test (OGTT), ambulatory blood pressure monitoring(ABPM) data including 24-hour mean systolic blood pressure(mSBP) and 24-hour mean diastolic blood pressure(mDBP) were collected. Then the relationship of IGT and myocardial remodeling related parameters were analyzed. Results The rate of diastolic dysfunction was higher in the IGT combined with hypertensive group(74% ) compared with the hypertensive group( 39% )( x2 = 6. 5, P ＜ 0. 05 ). The rate of diastolic dysfunction was higher in the IGT group( 34% ) compared with the normal group( 10% ) (x2 = 5.2,P ＜0. 05). The rate of Left Ventricular Hypertrophy (LVH)in the IGT combined with hypertensive group (24%) was higher than the other three groups (Hypertension group 7%, IGT group 0, Normal group 0) (x2 =4.561,P ＜0.05), and there was no significance between the rest three groups (P ＞0.05).Stepwise multiple regression showed age and 2 Hours' Postprandial Blood Glucose were independent risk factors of E/A ratio. Conclusions These results suggested that IGT is a possible contributor to left ventricular hypertrophy and diastolic dysfunction, and is one of the histopathology of left ventricular remodeling.

OBJECTIVETo explore use of retroviral vector in gene therapy of hepatitis B.

METHODSThe recombinant vector Plxsn-HBs was constructed by inserting HBV S gene into pLXSN. The pseudovirus, which was produced from PA317 after transferring with pLXSN-HBs by electroporation, were frozen at different temperature. The activities of the pseudovirus to infect eukaryotic cells and express antigen were determined by comparing the numbers of G418-resistant clones and assaying HBsAg in the supernatant of the cells with ELISA after infection HepG2, NIH3T3 and 293 cells.

RESULTSIt was hard to find changes in HBsAg amount at different intervals and different temperatures. G418 resistant clones, however, were variable. When frozen at -20 degrees C, the numbers of clones were half less than that of the beginning after 6 months, few clones were formed after 12 months, and no clone was found after 24 months. When frozen at -40 degrees C, the numbers of clones were 121, 332 and 89 42, 137 and 43 for HepG2, NIH3T3 and 293 cell lines at 12 and 24 months, respectively. When frozen at -70 degrees C, the numbers of clones were 159 463 and 112 for HepG2, NIH3T3 and 293 cell lines at 24 months, respectively. There was no statistical difference compared to that of zero months.

CONCLUSIONSThe activity of the peseudovirus to infect eukaryotic cells and expressed antigen was not changed after 2 years frozen at -70 degrees C.