Dynamic human exposure to airborne bacteria-associated antibiotic resistomes revealed by longitudinal personal monitoring data.

Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, ß-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

Cost-effectiveness analysis of dasatinib versus imatinib in pediatric philadelphia chromosome-positive acute lymphoblastic leukemia patients in China.

BACKGROUND: Dasatinib and imatinib are the recommended tyrosine kinase inhibitors (TKIs) for treating pediatric Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), and the one which has been approved indication in China is imatinib. Recently, clinical demand for Ph + ALL treatment is becoming unmet gradually with the increasing resistance of imatinib. There are some studies reporting the better efficacy and comparative safety of dasatinib compared with imatinib, but no economic comparison has been published. This study aims to supplement economic evidence by comparing the cost-effectiveness between imatinib and dasatinib in treating pediatric patients with Ph+ ALL in China, and to help clinical rational drug use via multi-dimensional value assessment. METHODS: A decision tree model combined with a 10-year Markov model were established based on the disease progression. The parameters were collected from published literatures and our hospital's electronic medical records. From the health system perspective, the incremental cost-effectiveness ratio (ICER) between the two treatment groups was calculated through cost-effectiveness analysis and then compared with the willingness-to-pay (WTP) threshold. The set WTP threshold in this study was 1 times per capita gross domestic product (GDP) of China, as recommended by the World Health Organization. Direct medical costs and quality-adjusted life years (QALYs) were calculated and discounted at 5%. The sensitivity analyses were conducted to assess the uncertainty and robustness of the results. RESULTS: The total costs were CNY 1,020,995.35 and CNY 1,035,788.50 in imatinib group and dasatinib group during the 10-year simulation, and the total QALYs were 2.59 and 4.84. Compared with the imatinib treatment group, the ICER was around CNY 6,575.78/ QALY, which was less than the set threshold CNY 70,892/ QALY. The sensitive analyses indicated the robustness of the results. CONCLUSIONS: The cost-effectiveness analysis shows the potential cost-effective advantages of adding dasatinib comparing with adding imatinib for pediatric Ph + ALL patients in China under the set WTP threshold, which indicates that those patients could achieve more QALYs by paying acceptable fee.

Local Electric-Field-Induced Spin Photocurrent in ReS2.

A spin-related photocurrent excited by circularly polarized light is observed near the electrodes on a few-layer ReS2 sample at room temperature. For both electrodes, the spatial distribution of the spin photocurrent shows a feature of two wings, with one positive and the other negative. In this work, it is suggested that this phenomenon arises from the inverse spin Hall effect due to the local electric field near the electrode. Bias voltage that modulates this field further controls the sign and magnitude of the spin photocurrent. Our research shows that the electric field near the electrodes has a significant impact on the spin transmission operation, and hence it could be taken into account for manufacturing spintronic devices in the future.

Deliberation-based learning: strengthening neonatal care in China.

This paper presents a case example from China, where detailed deliberations were instrumental in bringing together national and subnational managers to tailor implementation protocols for neonatal care strategies at provincial and county levels. The China National Health Development Research Center (CNHDRC) organised deliberations to support the formulation of strategies for improving early essential neonatal care for rural areas. The aim was to help counties, the lowest level jurisdiction in China, learn what could work locally, and to help provinces and the national government learn what should inform national policy and be disseminated widely in China's decentralised health system. It became clear that central-level stakeholders needed to learn how to help counties support the pilots. CNHDRC staff, national-level experts and academics visited pilot provinces and counties to discuss local policies, initiatives and challenges (including with patients), build a common understanding of the project and identify local support needs including by examining health records and observing health facilities. What followed were county-specific reports with priority interventions and implementation plans, which were further refined through county-level meetings. They helped central stakeholders better understand and address variations in county capacities and needs.

Observation and control of pseudospin switching in a finite-width topological photonic crystal.

Finite-size effect plays a significant role in topology photonics not to mention in reality all experimental setups are in finite-size. A photonic bandgap is opened in the topological edge state dispersion if a topological photonic crystal with finite width is considered, and the bandgap size relies on the finite-size effect. Pseudospin-preserving and pseudospin-flipping processes can be realized when a selectively switch of the pseudospin of edge states are customized by our designs. Our microwave experiments also successfully demonstrate pseudospin switch-on and -off behaviors in a finite-width photonic crystal. By combining photonic crystals with finite widths, a multi-tunneling proposal of topological photonic crystals can also be achieved. Our study of the finite-size effect will provide new approaches and thoughts to improve the development of topological photonic devices in the future.

Current-Induced Spin Photocurrent in GaAs at Room Temperature.

Circularly polarized photocurrent, observed in p-doped bulk GaAs, varies nonlinearly with the applied bias voltage at room temperature. It has been explored that this phenomenon arises from the current-induced spin polarization in GaAs. In addition, we found that the current-induced spin polarization direction of p-doped bulk GaAs grown in the (001) direction lies in the sample plane and is perpendicular to the applied electric field, which is the same as that in GaAs quantum well. This research indicates that circularly polarized photocurrent is a new optical approach to investigate the current-induced spin polarization at room temperature.

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat.

Purpose: To assess brain damage in a rat model of cerebral ischemia based on apparent diffusion coefficient (ADC) data obtained from multi-high b-values and evaluate the relationship between Aquaporin 4 (AQP4) expression and ADC. Methods: Thirty eight male Sprague-Dawley rats were randomized into two groups: (1) sham controls (n = 6) and (2) cerebral ischemia (successful model, n = 19). All rats underwent diffusion-weighted imaging (DWI) with both standard b-values and multi-high b-values (2,500-4,500 s/mm2) using a 3.0-T device. Standard ADC (ADCst) maps and multi-high b-value ADCs (ADCmh) were calculated, respectively. Aquaporin 4 expression was quantified using Western blot. Relative values of ADCst and ADCmh, AQP4 expression were compared between the sham group and the ischemia group. Correlations between ADC values and AQP4 expression were evaluated. Results: At 0.5 h after suture insertion, the value of ADCmh on the lesion was obviously decreased, and there was no difference in lesion volume when compared with ADCst. After reperfusion, besides similar regions where ADCst values decreased, we also found additional large values on ADCmh within the cortex of the ipsilateral side or surrounding the lesion. The lesion evolution of the large value on ADCmh was quite different from other indicators. But the total ADCmh values were still significantly associated with ADCst. The AQP4 protein expression level was appreciably increased after middle cerebral artery occlusion (MCAO), but there was no correlation between AQP4 expression either with ADCmh or ADCst. Conclusion: We found the large values on ADCmh during the progression of cerebral infarction is varied, but there was no correlation between ADCmh values and AQP4 expression. ADCmh may indicate the heterogeneity of ischemia lesions, but the underlying pathological basis should be further explored.

Rapid differential detection of subtype H1 and H3 swine influenza viruses using a TaqMan-MGB-based duplex one-step real-time RT-PCR assay.

Swine influenza is an economically important respiratory disease in swine, but it also constantly poses a threat to human health. Therefore, developing rapid, sensitive, and efficient detection methods for swine influenza virus (SIV) is important. By aligning the haemagglutinin (HA) gene sequences of SIVs circulating in China over a 10-year period, an H1 primer-probe set targeting both Eurasian avian-like H1N1 (EA H1N1) and pandemic 2009 H1N1 ((H1N1)pdm09) lineages plus a H3 primer-probe set targeting the prevalent human-like H3N2 (HL H3N2) subtype were designed. Subsequently, a TaqMan-MGB-based duplex one-step real-time RT-PCR (RT-qPCR) assay was established and evaluated. The duplex RT-qPCR has a detection limit of 5 copies/µL of HA plasmid for EA H1N1, (H1N1)pdm09, and HL H3N2 subtype SIVs, and its overall detection sensitivity of 100% and specificity of 91.67% matches that of traditional virus isolation through chicken embryo inoculation using experimentally infected mouse lung samples. The method showed high repeatability both within run and between runs, and there was no cross-reactivity against several other porcine viruses that are commonly circulating in China. Furthermore, the duplex RT-qPCR method revealed a higher prevalence of subtype H1 than subtype H3 in 166 nasal swabs from pigs collected from one slaughterhouse between October and December 2019. This assay could be very helpful in the rapid differential detection and routine surveillance of EA H1N1, (H1N1)pdm09, and HL H3N2 SIVs in China.

Dietary Acid Load and the Risk of Pancreatic Cancer: A Prospective Cohort Study.

BACKGROUND: Modern Western diets are rich in acidogenic foods. Human and in vitro studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap. METHODS: A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers. RESULTS: A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HRquartile 4 vs. 1: 1.73; 95% confidence interval (95% CI), 1.21-2.48; P trend = 0.001] in a nonlinear dose-response pattern (P nonlinearity = 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (P interaction = 0.018). Similar results were obtained for NEAP score. CONCLUSIONS: Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings. IMPACTS: This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.

Fe-cation Doping in NiSe2 as an Effective Method of Electronic Structure Modulation towards High-Performance Lithium-Sulfur Batteries.

The commercialization of Li-S batteries is hindered by the shuttling of lithium polysulfides (LiPSs), the sluggish sulfur redox kinetics as well as the low sulfur utilization during charge/discharge processes. Herein, a free-standing cathode material was developed, based on Fe-doped NiSe2 nanosheets grown on activated carbon cloth substrates (Fe-NiSe2 /ACC) for high-performance Li-S batteries. Fe-doping in NiSe2 plays a key role in the electronic structure modulation of NiSe2 , enabling improved charge transfer with the adsorbed LiPSs molecules, stronger interactions with the active sulfur species and higher electrical conductivity. Effective promotion of the sulfur redox kinetics and enhanced sulfur utilization were achieved under high areal sulfur loadings. The stronger interactions with LiPSs together with the unique 3D structure of Fe-NiSe2 /ACC also induced the transformation of Li2 S2 /Li2 S growth from conventional 2D films to 3D particles, significantly eliminating the barriers of solid nucleation and growth during the phase transition of liquid LiPSs to solid Li2 S2 /Li2 S. With a high sulfur loading of 9.9 mg cm-2 , the Fe-NiSe2 /ACC cathode enabled a high area capacity of 9.14 mAh cm-2 with a low average decay of 0.11 % per cycle over 200 cycles at 0.1 C.

Assay of extracellular matrix degradation and transmigration of chicken peripheral blood mononuclear cells after infection with genotype VII Newcastle disease virus in vitro.

Previous studies showed that, compared to genotype IV Newcastle disease virus (NDV), genotype VII NDV induced extensive extracellular matrix (ECM) degradation by up-regulating the protein expression of matrix metalloproteinase (MMP)-14 in chicken spleens. To investigate potential relationship between MMP-14 function and the ECM degradation, an in vitro peripheral blood mononuclear cells (PBMCs) infection model was established to study the effect of genotype VII NDV (JS5/05) infection on MMP-14 expression, ECM degradation and cell transmigration. The gene and protein expression levels of MMP-14 in NDV-infected chicken PBMCs were measured by quantitative real-time PCR (qRT-PCR) and Western blot, and the subcellular location of MMP-14 was analyzed using immunofluorescence microscopy. A fluorescence-based collagen degradation assay was optimized to measure ECM degradation in PBMCs. Additionally, parameters of a transwell-based transmigration assay were also optimized to determine chemotaxis and transmigration of virus-infected PBMCs. The results showed that JS5/05 up-regulated significantly the expression of MMP-14 in PBMCs at the mRNA and protein levels compared to genotype IV NDV (Herts/33). MMP-14 was transported towards the membrane and accumulated on the cell surface of the JS5/05-infected cells, whereas it remained mainly in the cytoplasm of the Herts/33-infected cells. Collagen degradation assay showed that JS5/05-infected cells exhibited significant collagen degradation compared to the Herts/33-infected cells, and the areas of collagen degradation co-localized with cell surface MMP-14 in the JS5/05-infected cells. The transwell-based transmigration system showed that the transmigration of the JS5/05-infected PBMCs was enhanced significantly compared to the Herts/33-infected cells. These results demonstrated that genotype VII NDV induced up-regulation and surface accumulation of MMP-14 in PBMCs, leading to enhanced ECM degradation and cell migration, and the assays optimized for this study were useful for investigating the regulation of cell behaviour by NDV.

N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses.

Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.

Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway.

BACKGROUND: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated. MATERIALS AND METHODS: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan-Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo. RESULTS: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo. CONCLUSION: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.

Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy and relieves hyperalgesia in diabetic rats.

The purpose of this study was to explore the role and mechanism of the PI3K/AKT/mTOR signaling pathway in painful diabetic neuropathy (PDN). The diabetes mellitus (DM) model was established by intraperitoneal injection of streptozocin into SD rats. After 3 weeks of modeling, the DM + LY group was treated with PI3K inhibitor, the DM + vehicle group was treated with DMSO, and the DM group was untreated. The paw mechanical withdrawal thresholds (MWT) was measured by Von Frey filaments, and the expression of PI3K/AKT/mTOR pathway-related proteins and autophagy marker proteins were analyzed by Western blotting. We found that 3 weeks after modeling, the MWT values of diabetic rats were significantly reduced, p-PI3K, p-AKT and p-mTOR proteins expression in the spinal cord was increased, and Beclin1 and LC3-II expressions were reduced (P < 0.05). After administration of PI3K inhibitor, the MWT values in DM + LY group were improved, and the expressions of p-PI3K, p-AKT and p-mTOR proteins in the spinal cord were decreased significantly, and the expressions of Beclin1 and LC3-II were increased (P < 0.05). However, there were no significant changes in the DM + vehicle group compared with the DM group (P > 0.05). Therefore, we conclude that activation of the PI3K/AKT/mTOR pathway and impaired autophagy may be key factors that cause PDN. Inhibition of the PI3K/AKT/mTOR pathway could promote autophagy activity and alleviate PDN.

The Development and Application of Virtual Reality Animation Simulation Technology: Take Gastroscopy Simulation System as an Example.

Virtual reality (VR) technology has a great potential in the field of medical simulation due to its immersion, interactivity and autonomy. It provides a new direction for integration and application in various disciplines. Combination of VR technology and clinical practice brings great convenience for medical education and experiments. Modern VR simulators can create realistic environments that capture minute anatomical details with high accuracy and solves the problem of difficulty in mass productions with traditional devices. Taking gastroscopy simulation system as an example, this paper discusses the development and application of VR animation technology, together with its excellent performance and current research status in surgery, scientific research, training and education.

Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis.

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

A two-stage retrospective analysis to determine the effect of entry point on higher exit of proximal pins in lateral pinning of supracondylar humerus fracture in children.

BACKGROUND: Kirschner wire fixation remains to be the mainstream treatment modality in unstable or displaced supracondylar humerus fracture in children, with divergent lateral pins being the most preferred due to their sufficient stability and decreased risk of ulnar nerve injury. However, the entry point at which the proximal lateral pin can be inserted to achieve a more proximal exit and maximum divergence has not been reported. This study retrospectively analyzed the characteristics and factors influencing the entry and exit points of the proximal lateral pins. METHODS: The study was divided into two stages. In stage one, the entry and exit points of the proximal pins of lateral pinning configuration were analyzed from intra-operative radiographs of children treated for extension-type supracondylar humerus fractures. The coronal and sagittal pin angles formed by the proximal pins were also measured. Using the findings of stage one, we intentionally tried to achieve a more proximal exit with the proximal pins in stage two. Comparisons between groups of patients treated by random and intentional pinnings were done statistically. RESULTS: In the first stage, 47 (29.2%) of the 161 proximal pins exited above the metaphyseal-diaphyseal junction (MDJ) region. Of these, 85.1% entered from lateral and posterior to the ossific nucleus of the capitellum (ONC). The pin angles averaged 58.4° and 90.5° in the coronal and sagittal planes respectively. In the second stage, 47 (65.3%) proximal pins in the intended group exited above the MDJ region, while only 32 (36%) in the random group exited above the MDJ region. CONCLUSION: While aiming at the upper border of the distal MDJ during pinning, lateral pins can easily achieve a higher, proximal exit above the MDJ if inserted from lateral and posterior to the ONC and parallel to the humeral shaft in the sagittal plane. Higher exit can also be easily achieved in younger patients and patients fixated with smaller diameter pins.