Effectiveness of next-generation sequencing for patients with advanced non-small-cell lung cancer: a population-based registry study.

BACKGROUND: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. MATERIALS AND METHODS: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. RESULTS: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). CONCLUSIONS: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.

[Methodology and progress in adjusting time-dependent covariates in clinical prediction models].

Adjusting time-dependent covariates into prediction models may help improve model performance and expand clinical applications. The methodology of handling time-dependent covariates is limited in traditional regression strategies (i.e., landmark model, joint model). For example, the number of predictors and practical situations which can be handled are restricted when using regression models. One new strategy is to use machine learning (i.e., neural networks). This review summarizes the methodology of handling time-dependent covariates in prediction models, such as applicable scenarios, strengths, and limitations, to offer methodological enlightenment for processing time-dependent covariates.

[Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks].

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

[The works of Zhang Wenzhong as the Shang Yao Feng Yu in the early Tang Dynasty].

Zhang Wenzhong, a famous Chinese medical doctor in the early Tang Dynasty, was granted a particular position as Shang Yao Feng Yu, for the Empress Wu Ze Tian dealing with medication. He was good at dealing with stroke in particular. He also had unique viewpoints towards medical prescriptions and skills. He wrote medical books and developed his own medical theories. All these were recorded in both the Book of Tang and the New Book of Tang. However, most of his works had been lost due to time and the frequent wars in the middle and late Tang Dynasty. Six medical prescriptions signed by Zhang Wenzhong were discovered in documents unearthed from the Dun Huang Sutra Cave. They were believed to be important archives of Zhang Wenzhong's writing and medical thoughts. In addition, some pieces of work found in the documents unearthed from Tu Yu Gou were suspected of being written by Zhang Wenzhong. This can be compared with his works cited in the handed-down documents, such as The Collection of Secret Prescriptions (Wai Tai Mi Yao Fang). This paper takes a textual research approach to examine the medical works of Zhang Wenzhong, comparing the handed-down documents with the unearthed documents to examine his medical achievements.

[Effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats].

Objective: To explore the effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats. Methods: The method of experimental study was adopted. The polyvinyl alcohol/sodium alginate microspheres (simple microspheres), P311 microspheres, and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) microspheres were prepared by water-in-oil emulsification, and then their morphology was observed under a light microscope/inverted fluorescence microscope. Chitosan solution was prepared, chitosan solution and ß-glycerol phosphate disodium hydrate were mixed to prepare simple thermosensitive hydrogels, and thermosensitive hydrogels loaded with simple microspheres or P311 microspheres were prepared by adding corresponding substances in simple thermosensitive hydrogels. The morphological changes of the prepared four liquids in the state of tilt was observed at 37 ℃. After being freeze-dried, the micromorphology of the prepared four liquids was observed under a scanning electron microscope. Eighteen 3-4-week-old male Sprague-Dawley rats were divided into normal group without any treatment, dressing group, chitosan group, hydrogel alone group, simple microspheres-loaded hydrogel group, and P311 microspheres-loaded hydrogel group, which were inflicted with one full-thickness skin defect wound on both sides of the back spine and were dealt correspondingly, with 3 rats in each group. Rats with full-thickness skin defects in the five groups were collected, the wound healing was observed on post injury day (PID) 0 (immediately), 5, 10, and 15, and the wound healing rates on PID 5, 10, and 15 were calculated. The wound and wound margin tissue of rats with full-thickness skin defects in the five groups on PID 15 and normal skin tissue in the same site of rats in normal group were collected, hematoxylin and eosin staining was conducted to observe the histological changes, immunohistochemical staining was performed to observe the expressions of CD31 and vascular endothelial growth factor (VEGF), and Western blotting was conducted to detect the protein expressions of CD31 and VEGF. The number of samples was all three. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni correction. Results: Simple microspheres were spherical, with loose and porous surface. The surfaces of P311 microspheres and FITC-BSA microspheres were smooth without pores, and the FITC-BSA microspheres emitted uniform green fluorescence. The diameters of the three microspheres were basically consistent, being 33.1 to 37.7 µm. Compared with chitosan solution and simple thermosensitive hydrogel, the structures of the two microspheres-loaded hydrogels were more stable in the state of tilt at 37 ℃. The two microspheres-loaded hydrogels had denser network structures than those of chitosan solution and simple thermosensitive hydrogel, and in the cross section of which microspheres with a diameter of about 30 µm could be seen. Within PID 15, the wounds of rats in the five groups were healed to different degrees, and the wound healing of rats in P311 microspheres-loaded hydrogel group was the best. On PID 5, 10, and 15, the wound healing rates of rats in dressing group and chitosan group were (26.6±2.4)%, (38.5±3.1)%, (50.9±1.5)%, (47.6±2.0)%, (58.5±3.6)%, and (66.7±4.1)%, respectively, which were significantly lower than (59.3±4.8)%, (87.6±3.2)%, (97.2±1.0)% in P311 microspheres-loaded hydrogel group (P<0.05 or P<0.01). The wound healing rates of rats in hydrogel alone group on PID 10 and 15, and in simple microspheres-loaded hydrogel group on PID 15 were (76.0±3.3)%, (84.5±3.6)%, and (88.0±2.6)%, respectively, which were significantly lower than those in P311 microspheres-loaded hydrogel group (P<0.05). The epidermis, hair follicles, and sebaceous glands could be seen in the normal skin of rats in normal group, without positive expressions of CD31 or VEGF. The wounds of rats in P311 microspheres-loaded hydrogel group on PID 15 were almost completely epithelialized, with more blood vessels, hair follicles, sebaceous glands, and positive expressions of CD31 and VEGF in the wounds than those of rats with full-thickness skin defects in the other four groups, and more protein expressions of CD31 and VEGF than those of rats in the other five groups. Conclusions: The P311 microspheres-loaded thermosensitive chitosan hydrogel can release the encapsulated drug slowly, prolong the drug action time, and promote wound healing in rats with full-thickness skin defects by promoting wound angiogenesis and re-epithelialization.

[Effects of composite laser technique combined with multipoint microinjection of triamcinolone acetonide in the treatment of hypertrophic scars in burn children].

Objective: To explore the effects of pulsed dye laser (PDL) and ultra-pulsed fractional carbon dioxide laser (UFCL) combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children. Methods: A retrospective cohort before-after control study in the same patients was conducted. From February 2019 to December 2020, a total of 67 burn children who met the inclusion criteria (32 males and 35 females, aged 1 to 12 years) with red hyperplastic scar at early stage, were treated in Hunan Provincial People's Hospital (1st Affiliated Hospital of Hunan Normal University). All the children were treated with composite laser technique (PDL and UFCL) combined with triamcinolone acetonide (hereinafter referred to as combined treatment). After 2 months, they received the second combined treatment. Before the first combined treatment and 6 months after the last combined treatment, the scar of children was evaluated with the patient and observer scar assessment scale (POSAS) by physicians and family members. Six months after the last combined treatment, the satisfaction of the patients' family members with the efficacy was recorded and the overall satisfaction rate was calculated. Adverse reactions were recorded throughout the treatment process. Data were statistically analyzed with paired sample t test. Results: Six months after the last combined treatment, the POSAS scores of children on the thickness, blood vessels distribution, color, surface roughness, texture, scope, and overall evaluation of scar evaluated by the physicians, and the POSAS scores of children on the color, degree of pain, degree of itching, hardness, thickness, shape and size, and overall evaluation of scar evaluated by the family members were significantly lower than those before the first combined treatment (with t values of 17.32, 16.73, 15.00, 14.91, 19.62, 28.74, 29.83, 17.43, 20.52, 29.01, 28.82, 24.91, 20.30, and 42.13, respectively, P<0.01). Six months after the last combined treatment, 62 (93%), 3 (4%), and 2 (3%) children's family members were very satisfied, satisfied, and relatively satisfied with the treatment effect, respectively, and the overall satisfaction rate was 97% (65/67). Six months after the last combined treatment, no scar thickening or infection occurred in all the wounds of children. Conclusions: Composite laser technique combined with multipoint microinjection of triamcinolone acetonide in the treatment of red hypertrophic scar at early stage in burn children can improve the appearance and texture of scar, reduce scar pain and pruritus, with high satisfaction of children's family members to the treatment effect and less adverse reactions.

[Methodology progress and challenges on assessing the appropriateness of real-world data].

From the perspective of data users, ensuring the relevance and reliability of big data in healthcare and medicine via assessments on data appropriateness is a prerequisite for generating high-quality real-world evidence, which could guarantee good representativeness and generalizability of real-world studies. This review summarized the quality dimensions, definitions, evaluation indexes and calculating methods of assessment on the appropriateness of real-world data (RWD) according to guidance from different countries and international organizations, as well as exploring the opportunities and challenges for better assessing RWD appropriateness.

[Effects of reactive oxygen species-responsive antibacterial microneedles on the full-thickness skin defect wounds with bacterial colonization in diabetic mice].

Objective: To study the effects of reactive oxygen species (ROS)-responsive antibacterial microneedles (MNs) on the full-thickness skin defect wounds with bacterial colonization in diabetic mice. Methods: Experimental research methods were adopted. The ROS-responsive crosslinker N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium (TSPBA) was first synthesized, and then the polyvinyl alcohol (PVA)-TSPBA MNs, PVA-ε-polylysine (ε-PL)-TSPBA MNs, PVA-TSPBA-sodium hyaluronate (SH) MNs, and PVA-ε-PL-TSPBA-SH MNs were prepared by mixing corresponding ingredients, respectively. The PVA-TSPBA MNs were placed in pure phosphate buffer solution (PBS) and PBS containing hydrogen peroxide, respectively. The degradation of MNs immersed for 0 (immediately), 3, 7, and 10 days was observed to indicate their ROS responsiveness. The standard strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) cultured in Luria-Bertani medium containing hydrogen peroxide were divided according to the random number table (the same grouping method below) into blank control group (without any treatment, the same below) and 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group with which PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL were co-cultured, respectively. Bacterial growth was observed after 24 h of culture, and the relative survival rate of bacteria was calculated (n=3). The mouse fibroblast cell line 3T3 cells at logarithmic growth stage (the same growth stage below) were divided into blank control group and 0 g/L ε-PL group, 1.0 g /L ε-PL group, 5.0 g /L ε-PL group, and 10.0 g /L ε-PL group in which cells were cultured in medium with the extract from PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, respectively. Cell growth was observed after 24 h of culture by optical microscopy, and the relative survival rate of cells was detected and calculated by cell counting kit 8 (CCK-8) assay to indicate the cytotoxicity (n=6). Both PVA-TSPBA MNs and PVA-TSPBA-SH MNs were taken, the morphology of the two kinds of MNs was observed by optical microscopy, and the mechanical properties of the two kinds of MNs were tested by microcomputer controlled electronic universal testing machine (denoted as critical force, n=6). Six male BALB/c mice aged 6-8 weeks (the same gender and age below) were divided into PVA-TSPBA group and PVA-TSPBA-SH group, with 3 mice in each group. After pressing the skin on the back of mice vertically with the corresponding MNs for 1 minute, the skin condition was observed at 0, 10, and 20 min after pressing. Another batch of 3T3 cells were divided into blank control group, 0 g/L ε-PL group and simple 5.0 g/L ε-PL group which were cultured with the extract of PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, and 5.0 g/L ε-PL+SH group which were cultured with the extract of PVA-ε-PL-TSPBA-SH MNs with 5.0 g/L ε-PL. The CCK-8 assay was performed to detect and calculate the relative survival rate of cells cultured for 24, 48, and 72 h to indicate the cell proliferation activity (n=6). Eighteen BALB/c mice were induced into diabetic mice model by high-sugar and high-fat diet combined with streptozotocin injection and then divided into sterile dressing group, 0 g/L ε-PL+SH group, and 5.0 g/L ε-PL+SH group, with 6 mice in each group. A full-thickness skin defect wound was made on the back of each mouse, and S. aureus solution was added to make a full-thickness skin defect wound with bacterial colonization model for diabetic mouse. The wounds of mice in 0 g/L ε-PL+SH group and 5.0 g/L ε-PL+SH group were covered with PVA-ε-PL-TSPBA-SH MNs with the corresponding concentration of ε-PL, and the wounds of mice in the 3 groups were all covered with sterile surgical dressings. The wound healing was observed on post injury day (PID) 0, 3, 7, and 12, and the wound healing rate on PID 3, 7, and 12 was calculated. On PID 12, the skin tissue of the wound and the wound margin were stained with hematoxylin and eosin to observe the growth of new epithelium and the infiltration of inflammatory cells. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, Mann-Whitney U test, and Bonferroni test. Results: With the extension of the immersion time, the PVA-TSPBA MNs in PBS containing hydrogen peroxide gradually dissolved and completely degraded after 10 days of immersion. The PVA-TSPBA MNs in pure PBS only swelled but did not dissolve. After 24 h of culture, there was no growth of S. aureus in 5.0 g/L ε-PL group or 10.0 g/L ε-PL group, and there was no growth of E. coli in 10.0 g/L ε-PL group. The relative survival rate of S. aureus was significantly lower in 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group than in blank control group (P<0.05 or P<0.01). The relative survival rate of E. coli was significantly lower in 5.0 g/L ε-PL group and 10.0 g/L ε-PL group than in blank control group (P<0.01). After 24 h of culture, the cells in blank control group, 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group all grew well, and the relative survival rate of cells was similar among the groups (P>0.05). The needle bodies of PVA-TSPBA MNs and PVA-TSPBA-SH MNs were both quadrangular pyramid-shaped and neatly arranged, and the needle bodies of PVA-TSPBA-SH MNs was more three-dimensional and more angular. The critical force of PVA-TSPBA-SH MNs was significantly higher than that of PVA-TSPBA MNs (Z=3.317, P<0.01). The MNs in PVA-TSPBA+SH group penetrated the skin of mice at 0 min after pressing, and the pinholes partially disappeared after 10 min and completely disappeared after 20 min, while the MNs in PVA-TSPBA group failed to penetrate the skin of mice. After 24, 48, and 72 h of culture, the proliferation activity of the cells in 5.0 g/L ε-PL+SH group was significantly higher than that of blank control group (P<0.05 or P<0.01). In sterile dressing group, the wounds of mice healed slowly and exuded more. The wound healing speed of mice in 0 g/L ε-PL+SH group was similar to that of sterile dressing group in the early stage but was faster than that of sterile dressing group in the later stage, with moderate exudation. The wound healing of mice in 5.0 g/L ε-PL+SH group was faster than that in the other two groups, with less exudation. The wound healing rates of mice in 5.0 g/L ε-PL+SH group were (40.6±4.2)%, (64.3±4.1)%, and (95.8±2.4)% on PID 3, 7, and 12, which were significantly higher than (20.4±2.7)%, (38.9±2.2)%, and (59.1±6.2)% in sterile dressing group and (21.6±2.6)%, (44.0±1.7)%, and (82.2±5.3)% in 0 g/L ε-PL+SH group (P<0.01). The wound healing rates of mice in 0 g/L ε-PL+SH group on PID 7 and 12 were significantly higher than those in sterile dressing group (P<0.05 or P<0.01). On PID 12, the wounds of mice in 5.0 g/L ε-PL+SH group were almost completely epithelialized with less inflammatory cell infiltration, the wounds of mice in 0 g/L ε-PL+SH group were partially epithelialized with a large number of inflammatory cell infiltration, and no obvious epithelialization but a large number of inflammatory cell infiltration was found in the wounds of mice in sterile dressing group. Conclusions: The composite MNs prepared by TSPBA, PVA, ε-PL, and SH can successfully penetrate mouse skin and slowly respond to ROS in the wound to resolve and release antibacterial substances, inhibit bacterial colonization, and promote the repair of full-thickness skin defect wounds with bacterial colonization in diabetic mice.

The relationship between famine exposure in early life and left atrial enlargement in adulthood.

BACKGROUND: Increased left atrium diameter (LAD) is associated with an elevated risk of cardiovascular diseases. The relationship between nutrition status and left atrial enlargement (LAE) is still unclear. The present study aimed to investigate the association of famine exposure in early life with LAE in adulthood. METHODS: Participants were divided into non-exposed, fetal, early, middle and late childhood exposed groups according to birth data. LAE was defined when LAD was ≥3.9 cm in women and ≥4.1 cm in men, or ≥2.3 cm m-2 by a sex-independent cut-off normalised for body surface area. Multivariate logistic regression was performed to calculate the odds ratio (OR) and confidence interval (CI) between famine exposure and LAE. RESULTS: In total, 2522 [905 male, mean (SD) age 59.1 (3.65) years] subjects were enrolled, including 392 (15.5%) LAE subjects. The prevalence of LAE in non-exposed, fetal, early, middle and late childhood exposed groups was 55 (10.8%), 38 (11.2%), 88 (18.1%), 102 (16.7%) and 109 (19.0%), respectively. Compared to the non-exposed group, the ORs for LAE were in fetal (OR = 0.956, 95% CI = 0.605-1.500, P = 0.847), late (OR = 1.748, 95% CI = 1.208-2.555, P = 0.003), middle (OR = 1.647, 95% CI = 1.140-2.403, P = 0.008) and early (OR = 1.630, 95% CI = 1.116-2.399, P = 0.012) childhood exposed groups after adjusting potential cofounders. When stratified by gender, smoking, body mass index, hypertension and diabetes, we found that the effect of famine exposure on LAE was only modified by diabetes (Pinteraction  = 0.007). CONCLUSIONS: Famine exposure during childhood stage might increase the risk of LAE in adults, and this effect interacts with diabetes.

Research Progress on Multiple Organ Damage and Mechanism of Cantharidin Poisoning.

ABSTRACT: Cantharidin poisoning has been proven to cause multiple organ damage. Acute circulatory failure, acute renal failure, and multiple organ failure resulting from cantharidin poisoning are the main causes of death for patients with cantharidin poisoning. However, research on the damage of main target organs and mechanism of cantharidin poisoning is not clear. This paper reviews the latest toxicological and pathological research literatures at home and abroad related to cantharidin poisoning and comprehensively summarizes the latest research progress on the toxicological and pathological damage and mechanism of the digestive system, circulatory system, respiratory system, urinary system, reproductive system, skin mucosa, immune system, and nervous system after cantharidin poisoning, to provide reference for improving the molecular toxicological mechanism of cantharidin poisoning and decision-making in the clinical intervention of cantharidin poisoning.

[Risk factors and prognosis of bronchopulmonary dysplasia associated pulmonary hypertension in preterm infants].

Objective: To analyze clinical features, prognosis and risk factors of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH). Methods: Clinical data of 338 infants with BPD were collected from the neonatal intensive care unit (NICU) in Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2016 and December 2018. These infants were divided into PH group and non-PH group. The clinical features and prognosis were compared between these two groups by Chi-square test or nonparametric test. Risk factors for BPD-PH were analyzed with binary logistic regression model. Results: Among the 338 BPD infants, 314 had no PH (92.9%) and 24 had PH (7.1%), with an average gestational age of (27.1±1.8) weeks, and 206 were males and 132 females.PH infants had younger gestational age ((26.4±2.1) vs. (27.2±1.7) weeks, t=2.201, P=0.028) and lower birth weight ((798±255) vs. (1 003±240) g, t=4.030, P<0.01), compared to non-PH infants. Besides, duration of mechanical ventilation and non-invasive positive pressure ventilation were higher in PH group than that in non-PH group (14.3 (2.1, 43.7) vs. 0.5 (0, 4.7) d, Z=-4.553, P<0.01; 30.0 (22.5, 64.2) vs. 15.0 (7.0, 26.0) d, Z=-4.838, P<0.01). The proportions of maternal hypertension, small for gestational age (SGA), late onset sepsis, ventilator associated pneumonia, hemodynamically significant patent ductus arteriosus (hsPDA), patent ductus arteriosus (PDA) requiring ligation, severe BPD and severe extrauterine growth retardation (EUGR) were higher in PH group than those in non-PH group ((20.8% (5/24) vs. 6.4% (20/314), 33.3% (8/24) vs. 7.6% (24/314), 54.2% (13/24) vs. 7.3% (23/314), 25.0% (6/24) vs. 6.1% (19/314), 75.0% (18/24) vs. 39.2% (123/314), 45.8% (11/24) vs. 1.9% (6/314), 66.7% (16/24) vs. 7.3% (23/314), 75.0% (18/24) vs. 45.5% (143/314), all P<0.05). Multivariate logistic regression analysis showed that maternal hypertension (OR=12.950, 95%CI: 1.740-96.385), severe bronchopulmonary dysplasia (OR=10.160, 95%CI: 2.725-37.884), SGA (OR=4.992, 95%CI: 1.432-16.920), PDA requiring ligation (OR=19.802, 95%CI: 3.297-118.921), severe EUGR (OR=20.316, 95%CI: 2.221-185.853) were independent risk factors of BPD associated PH. In the 24 infants with PH, all 7 mild PH infants and 8 moderate PH infants survived, while 4 out of 9 severe PH infants died. Among the survivors, the longest duration of oxygen therapy was up to the corrected gestational age of 1 year and 2 months. Conclusions: PH is a severe complication of BPD, and associated with higher mortality and poor prognosis. Echocardiography screening and regular post-discharge follow up are recommended for BPD infants with risk factors of PH.

[Common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities].

Objective: To investigate the clinical efficacy of common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities. Methods: Twenty patients (22 knees) with severe valgus deformities were prospectively and continuously included in Fujian Province Hospital from January 2010 to January 2016. Medial parapatellar arthrotomy, femoral distal resection using the intramedullary cutting guide with 3° to 5° of valgus and the common peroneal nerve "pre-release" was performed, the patella was routinely resurfaced. A common peroneal nerve checking was performed (LSUHSC system), then, these outcomes were collected independently using visual analogue scale (VAS) of pain, Knee Society Score (KSS), Hospital for Special Surgery Knee Score (HSS), range of motion of knees (ROM), femorotibial angle (FTA), hip-knee-ankle angle (HKA), condylar-hip angle (CHA), plateau- ankle angle (PAA). The paired t test was used to compare the data before and after the operation. Results: Patients were followed up for 18 to 55 (mean, (38±8) months). According to Krackow's classification, all cases were typed Ⅱ. All the patients had a completely normal motor (grade 5) and sensory (LSUHSC score was 5) nerve function of common peroneal nerve postoperatively. No decrease or loss in muscle strength and cutaneous sensation associated with common peroneal nerve was found. The VAS of pain, KSS, HSS, ROM, HKA, CHA, and PAA were all improved after the operation when compared with those before the operation (t=21.602, -70.238, -82.455, -20.560, 16.058, 9.682, 3.439, all P<0.05). The alignment of lower limbs was corrected basically, and the FTA decreased from 31.7°±8.0° before operation to 5.0°±2.0° at the last follow-up, the differences was statistically significant (t=16.725, P<0.05). No common peroneal nerve palsy and transient or late-onset palsy occurred, and no revision was needed for instability during the follow-up in all the patients. Conclusion: Common peroneal nerve "pre-release" for severe valgus knees may be an effective method in protecting the nerve.

[Correlation between cone-beam CT images of the third and fourth cervical vertebrae and age in female skeletal class â patients aged between 9 and 17 years in Qingdao].

Objective: To analyze the correlation between the age and the cone-beam CT (CBCT) images of the third and fourth cervical vertebrae in female skeletal class Ⅰ patients aged between 9 and 17 years, and to establish a quantitative evaluation method for calculating the age. Methods: CBCT images of 108 female skeletal class Ⅰ patients aged between 9 and 17 years were collected from Qingdao Stomatological Hospital from September, 2017 to March, 2019. The two-dimensional linear values (AH: height of anterior edge of vertebral body; H: height of middle part of vertebral body; PH: height of posterior edge of vertebral body; AP: width of vertebral body), the two-dimensional linear ratio values (AH/PH, AH/AP, AH/H, H/AP, H/PH, PH/AP) and the three-dimensional volume values of the third vertical vertebrae (C3) and the fourth vertical vertebrae (C4) were measured. By Exponential transformation of measurements and multiple linear regression analysis, the optimal index for evaluating age were screened, and the fitting degree of multiple linear regression equation (R(2)) and the accuracy of age estimation (SEE) were compared. CBCT images of 27 female skeletal class Ⅰ patients aged from 9 to 17 years were added from Qingdao Stomatological Hospital between April, 2019 and July, 2019, by which the accuracy of the regression equation was verified. Results: Multiple linear regression equation for age estimation based on two-dimensional linear indexes was as follows: Y=-113.928+33.743×e(AH)(3)(/100)+58.844×e(PH)(4)(/100)+20.590×e(AP)(4)(/100)( "e" was a natural constant, e≈2.718), R(2)=0.745, SEE=1.31. Multiple linear regression equation for age estimation based on two-dimensional linear ratio indexes was as follows: Y=-0.076-2.284×e(A)H(3)/PH(3)+3.227×e(A)H(3)/AP(3)+2.149×e(A)H(3)/H(3)+1.961×e(A)H(4)/H(4), R(2)=0.576, SEE=1.70. Multiple linear regression equation of age estimation by the volume index was as follows: Y=-16.828+22.184×e(V)(3)(/10 000), R(2)=0.555, SEE=1.71. The data of 27 new patients were tested. The CBCT measurement index of C3 and C4 vertebral bodies inferred the fitting degree (R(2)) and accuracy (SEE) of the equation of the age estimation. The two-dimensional linear value was superior to the two-dimensional linear ratio and the latter was superior to the three-dimensional volume value. The standard error of the estimate about them was 1.74, 2.00 and 2.37, respectively. Conclusions: The two-dimensional linear index of CBCT images of C3 and C4 could be used to estimate the age of 9 to 17-year-old female skeletal class Ⅰ patients, and the accuracy of the method was higher than that of two-dimensional ratio index and three-dimensional volume index.

Overexpression of miR-145-5p alleviated LPS-induced acute lung injury.

Acute lung injury (ALI) is a disease with high incidence and no effective therapeutic treatments. miR- 145-5p has been reported to be aberrantly expressed in lung injury tissues, suggesting a potential role in the progression and development of ALI. To validate this hypothesis and explore the underlying mechanism, a mouse model of ALI was established using lipopolysaccharide (LPS). Hematoxylin and eosin (Hand E) staining verified the successful establishment of mouse model with ALI. Levels of interleukin (IL)-1ß, IL- 6, tumor necrosis factor α (TNF-α) and myeloperoxidase (MPO) were detected by both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Mouse type II alveolar epithelial cells (AT II) were isolated and treated with LPS. miR-145-5p was significantly down-regulated both in mice with acute lung injury and LPS-induced AT II cells. Dual luciferase assays confirmed miR-145-5p could target and regulate Toll Like Receptor 4 (TLR4). Further analysis showed that miR-145-5p overexpression decreased the expression levels of IL-1ß, IL-6 and TNF-α in LPS-induced AT II cells. miR-145-5p overexpression also blocked the LPS-induced activation of nuclear factor kappa B (NF-κB) pathway and reactive oxygen species (ROS) accumulation in AT II cells. Finally, in ALI mouse model, miR-145-5p overexpression alleviated lung tissue injury, decreased the expression levels of IL-1ß, IL-6 and TNF-α and reduced MPO activity. In conclusion, miR-145-5p participated in the progression and development of ALI by decreasing the production of pro-inflammatory cytokines, inhibiting NF-κB pathway and suppressing ROS accumulation, shedding light on miR-145-5p as a potential therapeutic target for the treatment of ALI.

Continuous femoral nerve block and patient-controlled intravenous postoperative analgesia on Th1/Th2 in patients undergoing total knee arthroplasty.

The purpose of this study is to observe and compare the effects of continuous femoral nerve block (cFNB) and patient-controlled intravenous analgesia (PCIA) on postoperative analgesia and Th1/Th2 in patients undergoing total knee arthroplasty (TKA). Forty-six TKA were selected and randomly divided into two groups: the cFNB group and PCIA group. Patients in the two groups all underwent general anesthesia using a laryngeal mask. In the cFNB group, the femoral nerve block and catheterization were performed after induction of general anesthesia: 0.375% ropivacaine hydrochloride with a 20 mL loading dose was provided. After the end of the operation, the electronically controlled analgesia pump was connected. In the PCIA group, fentanyl with a 0.05 mg loading dose was provided and the electronic controlled analgesia pump was connected at the end of the operation. Venous blood was collected before anesthesia (T0), 1 h postoperatively (T1), 24 h postoperatively (T2) and 48 h postoperatively (T3). Th1/Th2 was calculated and analyzed by flow cytometry, and other indexes of these time points were recorded. The results show that there was no significant difference between the two groups regarding changes in blood pressure, heart rate and postoperative sedation Ramsay score. There was no significant difference in Th1 percentages (Th1%), Th2 percentages (Th2%) and ratios of Th1-to-Th2 (Th1/Th2) between the two groups at T0, T1 and T2 (P>0.05), while the Th1%, Th2% and Th1/Th2 of the PCIA group were lower than those of the cFNB group at T3 (P less than 0.05). It was concluded that cFNB represents a better postoperative analgesia for patients than PCIA, and has a lesser effect on Th1/Th2 balance, which can improve the outcome of patients.

The effect of DC+CIK combined therapy on rat liver cancer model and its modulatory effect on immune functions.

OBJECTIVE: Primary liver cancer is a sort of the most common solid tumors occurred in the digestive system. The incidence and mortality rate maintain at a high level, thus leading to heavy economic and psychological burdens for patients. Next-generation biological therapy, such as cellular immune treatment, improves the medicine efficacy. Cytokine-induced killer (CIK) cells can effectively clear residual tumor lesion and inhibit metastasis or recurrence. Dendritic cells (DCs) can specifically eliminate tumor cells via modulating cellular immune function of the host. This study aimed to investigate the function of DC+CIK combined treatment on rat liver model and its effect on immune functions. MATERIALS AND METHODS: RH-35 tumor cell was used to prepare live cancer model on Wistar rats, which were further divided into control, CIK and DC+CIK groups, in which rats received autograft CIK and DCs. Tumor size was later measured along with liver function index. The secretions of IFN-γ, IL-4, and TNF-α were measured by Real-time PCR and Western blotting. RESULTS: Both CIK and DC+CIK treatment significantly reduced tumor size and improved liver function, increased secretion of IFN-γ, IL-4, and TNF-α, decreased Bcl-2 expression and enhanced Bax expression (p < 0.05 compared to control group). DC+CIK combined therapy presented significantly better efficacy than CIK did. CONCLUSIONS: DC+CIK combined therapy can protect the host against tumors invasion via modulating body immune or liver function, regulating apoptosis/anti-apoptosis balance, which shows better efficacy than CIK alone, and can work as a novel biological therapeutic strategy for liver cancer.

[Textual research on Ð”Ñ .09319, a fragment of Dunhuang literature preserved in Russia].

Дх.09319, a fragment collected in the page 150 of Volume 14 of Dunhuang Literature Preserved in Russia, is damaged around the page, and only 6 lines of the text are remained. It is one of versions of San bu jiu hou lun (Treatise on Three Positions and Nine Indicators) in Su wen (Plain Questions), and different from another version of Dunhuang, Дх.00613+ P.3287. The two versions cannot be spliced together, but the former can supplement the texts of the latter. In addition, Дх.09319 is also significant to the collation of the missing popular version of San bu jiu hou lun of later generation.

The application value of continuous nursing for home oxygen therapy of patients in the stable phase of chronic obstructive pulmonary disease.

OBJECTIVE: To analyze the application value of continuous nursing in improving the effects of home oxygen therapy for patients in the stable phase of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Patients in the stable phase of COPD (n=106) were selected and divided into the control group and observation group based on parity digit of their admission number. There were 53 cases in each group. The patients in the control group received COPD health education at discharge, while the observation group received continuous nursing. The effect of home oxygen therapy in both groups after 3 months was compared. RESULTS: The compliance in the observation group for home oxygen therapy was significantly higher than that in the control group. Blood gas analysis and various indicators of pulmonary function in the control group at follow-up visits were not changed compared with those before. In contrast, partial pressure of blood oxygen and blood oxygen saturation of the observation group were lower than those before discharge. With the increasing partial pressure of carbon dioxide in arterial blood, the indicators of pulmonary function became lower than before. Comparing the various indexes between both groups at follow-up visits, the differences were statistically significant (p<0.05). The self-care ability and quality of life scores of patients in the observation group were higher than those of the control group, and the differences were statistically significant (p<0.05). CONCLUSIONS: By establishing health records and network platforms, continuous nursing can provide continuous health education and supervision for patients with COPD, which can effectively improve oxygen therapy compliance, self-care ability and quality of life. It has good application and promotional value.