[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens.

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

[Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency].

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

Global, regional, and national time trends in myocarditis-related mortality, 1990-2019: An age-period-cohort analysis.

OBJECTIVE: The aim of this study was to analyze the tendency of myocarditis mortality in 204 countries and areas during the last three decades and its connection with age, epoch, and birth cohort. MATERIALS AND METHODS: The Global Burden of Disease 2019 Study acquired a cause-specific myocarditis mortality estimate. The net drift, as well as the influence caused by age, period, and birth cohort, were evaluated by the age-period-cohort model. Additionally, we analyzed the tendency in research intensity and international collaboration across countries using 3,983 myocarditis-related publications from four periods during 1990-2019. RESULTS: During the last three decades, 101 of 204 countries and areas experienced an increase (net drifts ≥0.0%) or stagnant declines (≥-0.5%) in the death rate. In particular, increasing death rate was generally discovered in most countries whose Socio-demographic indexes (SDIs) are high and middle-high, such as the United States [net drift=2.11% (95% CI 1.71-2.51)] and Italy [2.65% (1.24-4.08)]. Countries with a higher number of deaths were more active in this field of study, such as the United States (237 publications), China (120), and Italy (73). The United States and Italy, whose total link strengths were 209 and 135, respectively, were more active in international collaborative studies. CONCLUSIONS: Despite the global decrease in myocarditis death rate during the last three decades, negative period and cohort effects and elevated mortality were discovered in numerous countries, especially in those whose SDIs were high, and the age distribution of deaths shifted from adolescent to middle-aged and older populations. We also observed a decline in myocarditis research in some countries with increased mortality.

[Comparison on the efficacy of Chinese-made novel-designed mechanical-locked and elastic self-locked transcatheter edge-to-edge repair system in the treatment of patients with functional mitral regurgitation].

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.

Evidence for Band Renormalizations in Strong-Coupling Superconducting Alkali-Fulleride Films.

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

Measurement of the Electric Dipole Moment of

The permanent electric dipole moment (EDM) of the ^{171}Yb (I=1/2) atom is measured with atoms held in an optical dipole trap. By enabling a cycling transition that is simultaneously spin-selective and spin-preserving, a quantum nondemolition measurement with a spin-detection efficiency of 50% is realized. A systematic effect due to parity mixing induced by a static E field is observed, and is suppressed by averaging between measurements with optical dipole traps in opposite directions. The coherent spin precession time is found to be much longer than 300 s. The EDM is determined to be d(^{171}Yb)=(-6.8±5.1_{stat}±1.2_{syst})×10^{-27} e cm, leading to an upper limit of |d(^{171}Yb)|<1.5×10^{-26} e cm (95% C.L.). These measurement techniques can be adapted to search for the EDM of ^{225}Ra.

Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placental exosomes in the maternal circulation across gestation.

The article "Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placental exosomes in the maternal circulation across gestation, by J. Liu, S.-Z. Wang, Q.-L. Wang, J.-G. Du, B.-B. Wang, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 2036-2043-DOI: 10.26355/eurrev_201804_14733-PMID: 29687860" has been retracted by the authors due to inaccuracies related to the misuse of data and Table I. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14733.

[Correlation analysis of cervical spine dysfunction, pain and muscle strength in office workers].

Objective: To expore the correlation between neck disability, neck pain and muscle strength in cervical pondylosis of office worker, and to provide scientific basis for the prevention and treatment of cervical spondylosis. Methods: In April 2021 ,234 patients with cervical spondylotic myelopathy treated in the Subsidiary Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine from April 2015 to April 2017 were selected, the correlation between Neck Disability Index (NDI) score, neck pain and muscle strength was analyzed using the Spearman rank correlation method. Mann-Whitney U test was used to compare the difference of maximum muscle strength of isometric contraction. Results: NDI score was negatively correlated with neck flexion, extension, and muscle strength in the left and right flexion directions (r(s)=-0.164, -0.169, -0.222, -0.176, P=0.012, 0.010, 0.001 , 0.007). In mild and moderate functional disorder patients, the muscle strength in flexion, extension and left and right flexion direction was greater, the difference was statistically significant (P <0.01). Conclusion: There is a negative correlation between cervical functional disorder and cervical muscle strength in office workers, suggesting that strengthening cervical muscle strength may be a way to improve cervical spine function.

CT and MRI features in 22 cases of primary malignant thymic germ cell tumours.

AIM: To analyse the computed tomography (CT) and magnetic resonance imaging (MRI) features of malignant thymic germ cell tumours (GCTs), in order to improve the accuracy of diagnosis of these tumours. MATERIALS AND METHODS: Twenty-two patients (20 men, two women; age, 28 ± 8.64 years) with malignant thymic GCTs confirmed at histopathology were enrolled retrospectively, and their CT and MRI findings were analysed. RESULTS: According to the CT findings, malignant thymic GCTs usually manifest as a bulky mass that typically grows to both sides of the midline (20/22, 90.9%), with irregular shape (15/22, 68.2%), lobulation (12/22, 50%), ill-defined margin (9/22, 40.9%), and incomplete capsule (21/22, 95.5%). Twenty masses revealed heterogeneous density with multifocal necrosis or cystic change in 19 (86.4%). Most cases (16/18, 88.9%) showed mild to moderate enhancement, and the branch-like vessel was found in 14 (14/18, 77.8%) cases. The minimum apparent diffusion coefficient (ADCmin) and mean apparent diffusion coefficient (ADCmean) values in 14 patients were (1.13 ± 0.45) and (1.37 ± 0.49) × 10-3 mm2/s, respectively. Compared with CT findings, the incidences of an incomplete capsule, heterogeneous signal, and necrotic or cystic change on MRI images occurred in all patients with malignant thymic GCT. In addition, peritumoural oedema was found in all 14 (100%) cases. CONCLUSION: MRI is superior to CT in showing incomplete capsule, peritumoural oedema, heterogeneous signal, and necrotic or cystic change of GCTs. Branch-like enhancement and multifocal necrosis may help the diagnosis of malignant thymic GCTs.

[Influence of correction degree on the clinical effect of valgus knee after total knee arthroplasty].

Objective: To investigate the influence of correction degree on the clinical effect of valgus knee after total knee arthroplasty(TKA). Methods: Clinical data of 91 patients with unilateral valgus knee who underwent TKA from January 2015 to December 2018 at Department of Orthopaedic Surgery,Zhongda Hospital,Southeast University were retrospectively analyzed. According to postoperative hip-knee-ankle angle(HKA),these patients were divided into neutral group (-3°≤HKA≤3°) and residual valgus group(HKA>3°). There were 70 patients in the neutral group,with a median age of 71.5 years(range:57 to 91 years),and 21 patients in the residual valgus group,with a median age of 71.5 years(range:60 to 85 years). The postoperative clinical indicators,including the range of motion (ROM),American Knee Society score(KSS),Western Ontario and McMaster University(WOMAC) osteoarthritis index,forgotten joint score (FJS-12) were collected. Meanwhile,the imaging indexes of femoral angle,tibial angle,femoral prosthesis flexion angle,tibial prosthesis posterior slope angle,patella tilt angle,congruence angle were also collected. Additionally,postoperative complications were recorded. The clinical data were analyzed by independent sample t test,Mann-Whitney U test or χ2 test. Results: There were no differences between the two groups in postoperative ROM (122.5°±8.5° vs. 119.4°±7.1°,t=1.534,P=0.128),KSS(159.8±8.9 vs. 150.0±8.9,t=-0.103,P=0.918),WOMAC osteoarthritis index(10.0(3.0) vs. 9.0(5.0),Z=-0.733,P=0.464),FJS-12(52.1(8.4) vs. 50.1(7.5),Z=-0.594,P=0.553)and femoral angle(94.0°(4.0°) vs. 94.0°(5.0°),Z=-0.209,P=0.835),tibial angle(90.0°(3.0°) vs. 91.0°(2.5°),Z=-1.226,P=0.220),femoral prosthesis flexion angle(3.0°(1.0°) vs. 3.0°(1.0°),Z=-0.652,P=0.514),tibial prosthesis posterior slope angle(4.0°(2.0°) vs. 4.0°(2.0°),Z=-0.763,P=0.445),patella tilt angle(9.0°(3.0°) vs. 9.0°(3.5°),Z=-1.429,P=0.153),congruence angle(14.0°(4.0°) vs. 15.0°(4.0°),Z=-1.690,P=0.091). However,abnormal proportions of patella tilt angle(33.3% vs.11.4%,χ²=5.630,P=0.018) and congruence angle(38.1% vs.17.1%,χ²=4.136,P=0.042) were apparent in the residual valgus group. The patients were follow-up for (32.1±5.2) months(range:24 to 40 months). Six weeks after operation,one case of joint stiffness occurred in the residual valgus group, which was improved after manual relaxation and rehabilitation exercises. At the last follow-up,two cases in the residual valgus group suffered patella instability which were fixed by patella braces and strengthening of the medial femoral muscles. There were no cases requiring reoperation for dislocation of patella,joint instability and aseptic loosening of the prosthesis in both groups. Conclusions: Residual valgus after TKA for valgus knee has no significant effect on the short-term clinical outcome,but it is more likely to cause abnormal proportions of patella tilt angle and congruence angle which may induce the risk of postoperative patella instability. The mid-and long-term outcomes need to be further investigated.

A combination of genome-wide association study and selection signature analysis dissects the genetic architecture underlying bone traits in chickens.

The bones of chicken play an important role in supporting and protecting the body. The growth and development of bones have a substantial influence on the health and production performance in chickens. However, genetic architecture underlying chicken bone traits is not well understood. The objectives of this study are to dissect the genetic basis of bone traits in chickens and to identify valuable genes and genetic markers for chicken breeding. We performed a combination of genome-wide association study (GWAS) and selection signature analysis (fixation index values and nucleotide diversity ratios) in an F2 crossbred experimental population with different genetic backgrounds (broiler × layer) to identify candidate genes and significant variants related to femur, shank, keel length, chest width, metatarsal claw weight, metatarsal length, and metatarsal circumference. A total of 545 individuals were genotyped based on the whole genome re-sequencing method (26 F0 individuals were re-sequenced at 10 × coverage; 519 F2 individuals were re-sequenced at 3 × coverage). A total of 2 028 112 single-nucleotide polymorphisms (SNPs) remained to carry out analysis after quality control and imputation. The integration of GWAS and selection signature analysis indicated that all significant SNPs responsible for bone traits were mainly localized on chicken chromosomes 1, 4, and 27. Finally, we identified 21 positional candidate genes that might regulate chicken bone growth and development, including LRCH1, RB1, FNDC3A, MLNR, CAB39L, FOXO1, LHFP, TRPC4, POSTN, SMAD9, RBPJ, PPARGC1A, SLIT2, NCAPG, NKX3-2, CPZ, SPOP, NGFR, SOST, ZNF652, and HOXB3. Additionally, an array of uncharacterized genes was identified. The findings provide an in-depth understanding of the genetic architecture of chicken bone traits and offer a molecular basis for applying genomics in practical chicken breeding.

[Impact of enhanced recovery after surgery strategy on early postoperative quality of recovery in patients undergoing laparoscopic surgery for gynecologic malignancy].

Objective: To investigate the impact of perioperative anesthesia management with enhanced recovery after surgery (ERAS) strategy on postoperative recovery in patients undergoing laparoscopic surgery for gynecologic malignancy. Methods: Ninety patients undergoing laparoscopic surgery for gynecologic malignancies from April 2018 to April 2019,aged 18-65 years,with American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, were recruited and randomly divided into two groups (n=45) using a random number table:ERAS group (group E) and control group (group C). Patients in group E received general anesthesia combined with transverses abdominis plane block and a series of interventions to optimize anesthetic and perioperative management, while patients in group C were treated with routine anesthesia management. Quality of Recovery-40 questionnaire (QoR-40) was administered to assess the early postoperative quality of recovery on 1 day before surgery, and at 24 and 48h after surgery. C-reactive protein (CRP) before and after the operation were evaluated. The incidence of nausea, vomiting and shivering, the time of first exhaust, ambulation, resumption of normal diet, postoperative hospital stay and complications were recorded. Results: The scores of QoR-40 [M(Q1, Q3)] in Group E were 175(171, 179) and 185(183, 189) at 24 h and 48 h after operation, which were higher than those in group C [162(160, 167) and 180(179, 183)] (both P<0.01). The levels of CRP in both group E and group C increased at 24 h and 72 h after operation. Moreover, the extent of increasing level of CRP in group C was much higher than that in group E [(39.8±18.0) mg/L vs (13.4±6.3) mg/L, (16.6±8.6) mg/L vs (6.7±2.5) mg/L] at 24 h and 48 h after operation (both P<0.01). Compared with group C, the numerical rating scale (NRS) for nausea decreased significantly in group E [0(0, 2) vs 3 (0, 5), P<0.01]. Meanwhile, the incidence of vomiting and shivering in group E was lower than that in group C [8.9% (4/45) vs 26.7% (12/45); 11.1% (5/45) vs 31.1% (14/45); both P<0.05]. The time of first exhaust, ambulation and resumption of normal diet in group E was (14±6) h, 6(6, 13) h and 1(1, 2) d, respectively, which was markedly shorter than that in group C [(25±10) h, 21(19, 27) h and 3(2, 3) d] (all P<0.01). Overall, the postoperative length of hospital stay reduced significantly for patients who followed the ERAS protocol [7(5, 11) d vs 10(7, 14) d, P<0.01]. The incidence of postoperative complications was 17.8% (8/45) and 37.8% (17/45) in group E and group C, respectively, with a significant difference (P<0.05). Conclusion: Implementation of ERAS anesthesia management in gynecologic oncology patients undergoing minimally invasive surgery alleviates perioperative discomfort, decreases surgical stress response, and improves the early postoperative quality of recovery.

Genome-wide selection signal analysis of Australian Boer goat reveals artificial selection imprinting on candidate genes related to muscle development.

As one of the best-known commercial goat breeds in the world, Boer goat has undergone long-term artificial selection for nearly 100 years, and its excellent growth rate and meat production performance have attracted considerable worldwide attention. Herein, we used single nucleotide polymorphisms (SNPs) called from the whole-genome sequencing data of 46 Australian Boer goats to detect polymorphisms and identify genomic regions related to muscle development in comparison with those of 81 non-specialized meat goat individuals from Europe, Africa, and Asia. A total of 13 795 202 SNPs were identified, and the whole-genome selective signal screen with a π ratio of nucleotide diversity (πcase /πcontrol ) and pairwise fixation index (FST ) was analyzed. Finally, we identified 1741 candidate selective windows based on the top 5% threshold of both parameters; here, 449 candidate genes were only found in 727 of these regions. A total of 433 genes out of the 449 genes obtained were annotated to 2729 gene ontology terms, of which 51 were directly linked to muscle development (e.g., muscle organ development, muscle cell differentiation) by 30 candidate genes (e.g., JAK2, KCNQ1, PDE5A, PDLIM5, TBX5). In addition, 246 signaling pathways were annotated by 178 genes, and two pathways related to muscle contraction, including vascular smooth muscle contraction (ADCY7, PRKCB, PLA2G4E, ROCK2) and cardiac muscle contraction (CACNA2D3, CASQ2, COX6B1), were identified. The results could improve the current understanding of the genetic effects of artificial selection on the muscle development of goat. More importantly, this study provides valuable candidate genes for future breeding of goats.

Comparative efficacy and safety of PD-1/PD-L1 immunotherapies for non-small cell lung cancer: a network meta-analysis.

OBJECTIVE: PD-1/PD-L1 inhibitors are a relatively new class of immunotherapeutic drugs approved for advanced non-small-cell lung cancer. The purpose of this study was to conduct a network meta-analysis to compare the safety and efficacy of these immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We used Bayesian network meta-analysis methods to evaluate the efficacy and safety of the included treatments. We further analyzed subgroups based on PD-L1 expression level, histology type, and line of the treatment setting. RESULTS: We identified 19 RCTs, including 12,753 patients. In the analysis of all-comers, the pembrolizumab/chemotherapy combination ranked best for overall survival (OS) and progression-free survival (PFS). Durvalumab was the only ICI treatment that showed no benefit over chemotherapy. In the first-line setting only, in terms of OS, atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab ranked as the best treatments for patients with PD-L1 expression levels of ≥50%, 1-49%, and <1%, respectively. Nivolumab, atezolizumab, pembrolizumab, and durvalumab all had lower odds of grade 3 or greater treatment-related adverse events (TRAEs) compared to chemotherapy. With the addition of chemotherapy to any ICI regimen, the odds of TRAEs increased in a considerable and statistically significant way. CONCLUSIONS: While the pembrolizumab/chemotherapy combination was the most effective therapy in the overall cohort of all-comers, treatment preferences varied by treatment-line setting, tumor characteristics, and outcome of interest. In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.

A functional variant in the promoter region of IGF1 gene is associated with chicken abdominal fat deposition.

Insulin-like growth factor 1 (IGF1) plays an important role in the regulation of cell growth, proliferation, differentiation, and apoptosis. Previously several studies revealed that genotypes of chicken IGF1 c.-366A > C were significantly associated with abdominal fat weight and body weight in chickens. But the underlying mechanism is still unknown. To investigate the mechanism underlying the association, herein, we performed IGF1 gene mRNA expression profiling, a dual-luciferase reporter assay and electrophoretic mobility shift assay (EMSA). Quantitative real-time PCR results showed that IGF1 gene was widely expressed in 14 tissues. The mRNA expression levels of IGF1 gene in both abdominal fat and jejunum were significantly higher in fat broilers than in lean broilers. However, the opposite results were observed in the pancreas. The reporter gene assay showed that the promoter luciferase activity of allele A was significantly higher than that of allele C (P < 0.05). In addition, the luciferase activity of allele A promoted by the transcription factor AP1 and OCT1 was higher than that of allele C (P < 0.05). Electrophoretic mobility shift assay result showed that allele A binding to the transcription factor AP1 and OCT1 was stronger than that of allele C. All in all, our data indicated that the IGF1 gene c.-366A > C is a functional SNP responsible for chicken adipose deposition.

[Preventive medicine curriculum system in training program of clinical medicine in the era of Healthy China].

Objective: To understand the provision of preventive medicine curriculum system in the training programs of clinical medicine in the era of Healthy China. Methods: A total of 36 training programs of clinical medicine were selected from different areas of China for a statistical analysis on their basic information, involvement of concept of preventive medicine in program objectives, and provision of preventive medicine curriculum system. Results: Of all the 36 training programs of clinical medicine, 22(61%) have no mentions of prevention medicine in their program objectives; only one university's training program states preventive medicine together with basic medicine and clinical medicine as one of the three main disciplines. The total class hours for the core courses of preventive medicine (hygiene, medical statistics, epidemiology, evidence-based medicine, and social medicine) range from 80 to 252, with an average of (156.7±43.2) hours. The average percentage of class hours for preventive medicine courses among the total class hours is 4.3%±1.1% (range: 2.5%-7.5%), and obvious differences exist among universities. Conclusions: In current training programs of clinical medicine, the proportion of prevention medicine curriculum is insufficient, the percentage of hours for preventive medicine course is very low, and the differences among various universities are obvious. It is urgently needed to strengthen preventive medicine curriculum in training programs for clinical medical students in new era. It is suggested to further promote the concept of putting prevention first, improve the curriculum system of clinical medicine, intensify the integrated development preventive medicine and clinical medicine and pay attention to clinical research ability enhancement for the further improvement of training program of clinical medicine.

Three-dimensional evaluation of condylar morphology after closed treatment of unilateral intracapsular condylar fracture in children and adolescents.

PURPOSE: To investigate the condylar morphology after closed treatment of unilateral intracapsular condylar fracture in children and adolescents through three-dimensional evaluation and to explore the influence of age, types of fracture, follow-up period, treatment methods, and concomitant fractures on the treatment effectiveness. MATERIALS AND METHODS: The medical records of patients who underwent closed treatment for condylar fractures from January 2006 to December 2018 were reviewed. The fractured sides were included in the study group and the opposite healthy joints were included in the control group. The height of articular eminence, depth of glenoid fossa, length & width & thickness of condylar process, length & width of the ramus, and deviation of pogonion were measured three-dimensionally. RESULTS: 31 participants were included in the study. The length of condylar process was 2.10 ± 3.77 mm (P = 0.004) shorter, the depth of glenoid fossa was 1.09 ± 2.13 mm (P = 0.040) shallower, and the length of ramus was 1.55 ± 2.49 mm (P = 0.002) longer in fractured side than the ones in healthy side after closed treatment. The pogonion deviated 0.48 ± 1.7 mm to the fractured side, but no statistical significance was found (P = 0.129). CONCLUSIONS: Children had great growth potential to compensate the shortening of condylar process after intracapsular condylar fracture, so closed treatment could be an effective therapy for young children and adolescents.