Identification of key genes for atherosclerosis in different arterial beds.

Atherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.

Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis.

This study aims to investigate the mechanism of the anti-atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE-/- mice was observed using haematoxylin-eosin (HE) staining and oil red O (ORO) staining. The co-localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 µg/mL ox-LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK-8 assay. The co-localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p-mTOR/mTOR, p-4EBP1/4EBP1, p-P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT-PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q-Orbitrap high-resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE-/- mice. HYQT decreased the co-localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT-PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q-Orbitrap high-resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage-derived foam cell formation. It has been observed that HYQT and ox-LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1-SCARB1 signal axis, while taurine plays a significant role in lipophagy.

[Cost-effectiveness of HCV testing strategies for hepatitis C elimination in general population in China].

Objective: To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness. Methods: A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model. Results: Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable. Conclusions: Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

[Application of super-resolution and ultrafast ultrasound to reveal the characteristics of vascular blood flow changes after rat spinal cord injury at different segments].

Objective: To investigate the changes of spinal vascular blood flow in SD rats after cervical, thoracic and lumbar spinal cord injury (SCI) using super-resolution ultrafast ultrasound technology. Methods: A total of 9 SD rats were used to construct SCI models at different segments using a 50 g aneurysm clip. Super-resolution ultrafast ultrasound technology was used to perform vascular blood flow imaging on the spinal cord of rats before and after injury at 6 hours, obtaining quantitative information such as spinal cord vascular density and blood flow velocity. Results: Ultrasound imaging showed that after SCI, the vascular density in the thoracic segment decreased (18.16%±1.04%) more than in the cervical segment (11.42%±1.39%) and lumbar segment (13.88%±1.43%, both P<0.05). The length of the spinal cord with decreased vascular density in the thoracic segment [(4.80±0.34)mm] was longer than that in the cervical segment [(2.80±0.57)mm] and lumbar segment [(3.10±0.36)mm, both P<0.05]. After injury, the decrease of blood flow in the thoracic segment [(8.87±0.85)ml/min] was higher than that in the cervical segment [(4.88±0.56)ml/min] and lumbar segment [(6.19±0.71)ml/min, both P<0.05]. HE staining and Nissl staining showed that the proportion of cavity area after thoracic SCI (11.53%±0.93%) was higher than that in the cervical segment (4.90%±1.72%) and lumbar segment (7.64%±0.84%, both P<0.05). The number of Nissl bodies in the thoracic segment (18.0±5.3) was also lower than that in the cervical segment (32.3±5.1) and lumbar segment (37.0±5.6) (both P<0.05). Conclusions: There are different changes in vascular blood flow after SCI in different segments of rats. The same injury causes the most severe damage to blood vessels in the thoracic spinal cord, followed by the lumbar spinal cord, and the cervical spinal cord has the least damage.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

[Preliminary evaluation of immunogenicity and protective effect of multicomponent recombinant protein vaccine EPRHP014 against tuberculosis].

Objective: To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB. Methods: Three full-length Mycobacterium (M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M. tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results: Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance (P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group (P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group (P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group (P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group (P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups (P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant (P>0.05). Conclusion: Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Brain iron deposition is positively correlated with cognitive impairment in patients with chronic cerebral hypoperfusion: a MRI susceptibility mapping study.

AIM: To investigate the relationship of brain iron deposition with cognitive impairment in patients with chronic cerebral hypoperfusion (CHP). MATERIALS AND METHODS: Brain iron deposition was detected using quantitative susceptibility mapping (QSM), and cognitive function by neuropsychological tests including the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADLs), and verbal fluency tests in a total of 40 participants, 23 with CHP and 17 age- and sex-matched healthy participants without CHP (controls). RESULTS: The neuropsychological tests revealed that cognitive impairment (p<0.05) and susceptibility values (p<0.05) of the bilateral hippocampus (HP) and substantia nigra (SN) in CHP patients were significantly higher than those of the controls. The susceptibility values of bilateral HP and left putamen correlated closely with the scores of neuropsychological tests in the CHP patients (p<0.05, r2>0.1). The susceptibility values in the left putamen and bilateral HP were significantly higher in CHP patients with mild cognitive impairment (MCI; n=8) than those of CHP patients without MCI (n=15; p<0.05). CONCLUSIONS: The present findings indicated that brain iron deposition in specific areas may be responsible for the cognitive impairment in CHP patients, and that QSM is a useful tool to determine brain iron, predicting cognitive impairment in CHP patients.

[Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model].

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

[Annual progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis in 2022].

At present, the number of cases with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in China ranks fourth in the world, and the prevention and control situation is still serious. Chemotherapy, as the most important treatment for MDR/RR-TB, was studied and explored by domestic and foreign researchers in 2022. New chemotherapeutic drugs such as delpazolid, sutezolid, telacebec and independently developed anti-tuberculosis drugs such as pyrifazimine, sudapyridine and JBD0131 are still in clinical trials. The efficacy, safety, tolerability, adverse reactions and drug resistance of bedaquiline, linezolid, delamanid and pretomanid have been studied extensively. Meanwhile, different new chemotherapy regimens centered on new drugs have been explored in-depth by international scholars. In this article, we reviewed the progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis from October 2021 to September.

[Effects of Porphyromonas gingivalis injected through tail vein on the expressions of biomarkers in neural stem cells and neurons of wild-type rats hippocampus].

Objectives: To study the effects of Porphyromonas gingivalis (Pg) injected through tail vein on the molecular expression levels of biomarkers of neural stem cells (NSC) and neurons in the hippocampus of wild-type adult rats, and the effects on hippocampal neurogenesis. Methods: Eighteen male Sprague-Dawley (SD) rats were randomly divided into 3 groups based on the table of random numbers (n=6 in each group). In low-intensity group and high-intensity group, rats were injected intravenously through tail vein with 200 µl Pg ATCC33277 [1.0×103 and 1.0×108 colony forming unit (CFU), respectively] 3 times per week for 8 weeks. In the sham group, 200 µl of phosphate buffer saline (PBS) was given instead. Behavioral tests: the navigation and the exploration tests using Morris water maze (MWM) were applied to evaluate learning and memory ability of rats. Immunohistochemistry was performed to detect cells positively expressing nestin, doublecortin (DCX) and neuronal nuclei (NeuN) in the subgranular zone (SGZ) of rats in each group. Western blotting was used to evaluate the expression levels of nestin, DCX and NeuN in rat hippocampus. Results: Learning and memory abilities: on day 5 of navigation test, the lagency time was 22.83 (16.00, 38.34) s in the high-intensity group, significantly longer than the sham group [5.59 (5.41, 6.17) s] (t=-11.17, P<0.001). There were no significant differences between the low-intensity group [9.85 (8.75, 21.01) s] and the sham group (t=-6.83, P=0.080). Results in the exploration test showed that, in the high-intensity group, the number of fime crossing over the previous platform area within 60 s was 1.50 (1.00, 2.00), significantly less than the sham group [4.00 (2.75, 4.00)] (t=9.75, P=0.003); no significant differences between the low-intensity group [2.50 (2.00, 3.00)] and the sham one (t=4.50, P=0.382). Immunohistochemistry showed that the nestin+ cell density in the low-intensity group [(35.36±4.32) cell/mm2] and high-intensity group [(26.51±5.89) cell/mm2] were significantly lower than the sham group [(59.58±14.15) cell/mm2] (t=24.21, P=0.018; t=33.07, P=0.005); as for the mean absorbance of DCX+ cells, the low-intensity group (0.007±0.002) and the high-intensity group (0.006±0.002) were significantly lower than the sham group (0.011±0.001) (t=0.004, P=0.018; t=0.006, P=0.005); compared with the sham group [(1.13±0.14)×103 cell/mm2], the density of NeuN+ neurons in the high-intensity group [(0.75±0.08)×103 cell/mm2] was significantly reduced (t=0.38, P=0.017), and was not significantly changed in the low-intensity group [(0.88±0.19)×103 cell/mm2] (t=0.25, P=0.075). Western blotting results showed that, compared with the sham group, the expression levels of nestin, DCX, and NeuN were significantly reduced in the high-intensity group (t=0.74, P<0.001; t=0.18, P=0.014; t=0.35, P=0.008), but were not statistically changed in the low-intensity group (t=0.18, P=0.108; t=0.08, P=0.172; t=0.19, P=0.077). Conclusions: Pg injected through tail vein may reduce learning and memory abilities of wild-type rats, and may reduce the number of nestin, DCX, and NeuN-positive cells, and the protein expression levels of the above molecules in the hippocampus.

[Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia].

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

[Application of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection].

Objective: To evaluate the effect of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection. Methods: From June 2016 to December 2019, 12 patients with defect after resection of mouth floor cancer were treated with trifoliate flap design of radial forearm flap. All of these patients were T2 stage, included 9 well-differentiated squamous cell carcinoma (SCC) and 3 moderate differentiated SCC. The defect size ranged from 8.0 cm×6.0 cm to 5.0 cm×4.5 cm after resection of tumor and neck dissection. All defects were repaired with trifoliate flap design of radial forearm flap. The flap size ranged from 8.0 cm×2.0 cm to 4.0 cm×1.5 cm, the donor site was sutured directly on Z plasty. Results: All flaps completely survived well. Both the wound and the donor site were stage Ⅰ healing. With the average follow-up of 38.6 months, the swallowing and speech function were satisfactory. Conclusions: Trifoliate flap design of radial forearm flap can effectively repair the postoperative defect of mouth floor cancer, and the donor site can be directly sutured on Z plasty. This technique can avoid forearm scar caused by skin grafting and the formation of the second donor site.

[A comparative study of breast cancer mass screening and opportunistic screening in Chinese women].

Objective: To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer. Methods: This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants' characteristics and screening results of the two groups were compared by χ2 test, Fisher exact test or Wilcoxon rank-sum test. Results: A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ²=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ²=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ²=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ²=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ²=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ²=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ²=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ²=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ²=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ²=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ²=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ²=0.082, P=0.774). Conclusions: Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

[Standards of surgical clinical researches: Introduction of IDEAL framework].

Many breakthroughs in the field of surgical clinical researches have been achieved in China, but the overall quality is relatively limited, largely because of the insufficiency in standardization, rationality and scientificity of methodology. In consideration of the nature of surgical procedures and equipments, it is necessary to establish a set of methodological system, suitable for the high-quality clinical research in the surgical field. IDEAL collaboration has put forward a systematic methodological framework for innovation in surgical procedure and equipment. For the clinical research on surgical innovation, the IDEAL framework can be divided into five sequential stages, namely, Idea, Development, Exploration, Assessment and Long-term follow-up. In different stages, the difficulties to be faced, the problems to be solved, and the research design to be adopted are diverse and progressive. Although the IDEAL framework is not perfect, it is currently the best framework for surgical clinical research. While performing surgical clinical research, we should continue to think about how to improve the surgical clinical research methodology.

[A follow-up study of abnormal mutation in neonatal deafness gene screening].

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years' audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years' hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years' hearing follow-up. Conclusions: The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

[Evaluation of CT angiography vascular localization combined with refined three-dimensional printing in guiding the resection and reconstruction of complex oral cancer].

Objective: To evaluate the effect of vascular localization using computerized tomography angiography (CTA) combined with refined three dimensional (3D) printing in guiding the resection and reconstruction of complex oral cancer. Methods: From December 2013 to July 2017, the clinical data of 30 patients with complex oral cancer enrolled in the Hunan Cancer Hospital were retrospectively analyzed. 15 patients received CTA+ 3D assisted surgery, while the other 15 patients underwent traditional surgery. In CTA+ 3D assisted surgery group, CT and Magnetic Resonance Imaging (MRI) data were combined with CTA to print refined solid 3D model and surgical guide plate. The preoperative and intraoperative virtual surgical system and the operative experience were combined for preoperative evaluation and surgery. In traditional surgery group, preoperative evaluation and surgery were performed according to imaging data and surgeons' clinical experience. Operative time, intraoperative blood loss, hospital stay and local recurrence rate were compared between the two groups. Results: In CTA+ 3D assisted surgery group, one patient gave up surgical treatment after intuitively watching the lesion through the 3D model, and the remaining 14 patients underwent surgery as planned. All the 15 patients in traditional surgery group received surgery. But the preoperative plans of three patients were temporarily and passively modified due to insufficient preoperative evaluation. The average intraoperative blood loss was(320.1±27.2)ml in CTA+ 3D assisted surgery group and(430.2±30.3)ml in traditional surgery group. Mean operation time was(440.3±19.2)min and(552.2±23.3)min, respectively. Mean hospitalization time was (20.4±3.2)d and (25.1±3.7)d, respectively. The differences were all statistically significant (all P<0.05). 1 year and 3 years local recurrence rates were 9.1% and 28.6% in CTA+ 3D assisted surgery group, as well as 14.3% and 50.4% in traditional surgery group with statistical significance (P<0.05). Conclusion: For complex oral cancer patients with difficulty in opening the mouth or postoperative recurrence, CTA vascular localization combined with fine 3D printing technology has significant advantages in the surgical process, surgical effect and postoperative evaluation index compared with traditional method using imaging data and clinical experience.

[Congenital ear deformity screening and non-invasive correction effect analysis].

Objective:To synchronously perform external auricle examination during neonatal hearing screening, follow up auricle deformity with neonatal disease screening system, and calculate the incidence of auricle deformity, self-healing rate, correction rate, incidence of complications and the relationship with hearing loss in Zhuhai area. Method:According to the diagnostic criteria of auricle deformity, the newborns in Zhuhai Maternal and Child Health Hospital were examined on the spot within 2 months. The deformity auricle was registered and uploaded into the newborn hearing screening system. The newborns were followed up by short message notification 7 days after birth, and then compared with the photo uploading system again. At 14 days, the ears of those who could not self-heal were went on non-invasive correction, and collect of relevant data for summary analysis. Result:Among the 1 073 newborns(2 146 ears), 26(37 ears) with malformed ears were treated with auricular pattern correction.The corrective rates of newborns less than 14 days, 14-30 days and 31-60 days were 95%, 90% and 87% respectively, and the incidence of complications were 50%, 58% and 69%, respectively. Conclusion:The incidence of auricular deformities in neonates is high. The earlier correction the better. The ear deformity can be detected at the earliest stage and missed diagnosis can be avoided by simultaneous hearing screening and ear deformity screening. During the window period of 7-14 d, by monitoring the self-healing rate of the affected ear excessive medical correction can be avoided. By hearing screening system statistics, ear shape malformation is not directly related to hearing loss.