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Objective To differentiate urine derived pluripotent stem cells (iPSCs) into hair follicle stem cells (HFSCs) to construct a skin substitutes. Methods Human urinary cells isolated from a healthy donor were re-programmed into iPSCs. iPSCs were then induced into iPS-HFSCs. Immunocytochemistry and RT-qPCR were used to examine the characteristics of the induced iPS-HFSCs. Results The iPSCs induced from urine cells have characteristics as embryonic stem cells. iPSCs derived cells displayed the morphology, genes expression and phenotypes similar to iPS-HFSCs. Conclusions The urine cells are successfully reprogramed into iPSCs by four transcription factors, and iPSCs derived cells show characteristics similar to HFSCs.

Objectives: To investigate the changes in the pathogen spectrum and antimicrobial resistance over time in neonatal sepsis., Methods: The medical data were collected from the neonates who were diagnosed with sepsis in the Second Xiangya Hospital of Central South University from January 2010 to December 2019. The incidence rate of sepsis, the pathogen spectrum, and the characteristics of antimicrobial resistance were analyzed., Results: The incidence rate of neonatal sepsis was 4.02% (447/11 111). The top four pathogens detected were coagulase-negative staphylococci (CoNS), Klebsiella pneumoniae , Escherichia coli , and Candida. The incidence rate of sepsis and the pathogen spectrum showed no significant changes over time. Klebsiella pneumoniae was the most frequent pathogen in preterm infants, very low birth weight infants, and small-for-gestational-age infants, accounting for 33.9%, 29.5%, and 42.5%, respectively. CoNS, Klebsiella pneumoniae , and Escherichia coli had a high resistance rate to penicillins and third-generation cephalosporins., Conclusions: The incidence of neonatal sepsis is high, and the main pathogen is CoNS. The pathogens of neonatal sepsis have a high resistance rate to penicillins and third-generation cephalosporins. It is recommended to enhance the prevention and control of neonatal infection, strengthen the surveillance of pathogens, and further standardize the rational use of antibiotics.

Objectives: To study the clinical features and outcome of very preterm infants withdrawn from caffeine citrate at different time points., Methods: A retrospective analysis was performed on the medical data of the preterm infants with a gestational age of <32 weeks, who were hospitalized in the Division of Neonatology, the Second Xiangya Hospital of Central South University, from January 1, 2016 to November 30, 2020. According to the time of withdrawal from caffeine citrate, the infants who met the study criteria were divided into the group with withdrawal before the last week of hospitalization and the group with withdrawal within the last week of hospitalization. The two groups were compared in terms of clinical features, features of citric caffeine use, length of hospital stay and hospital costs, change in the intensity of respiratory support, and preterm complications., Results: A total of 403 preterm infants were enrolled, with 285 infants in the group with withdrawal before the last week of hospitalization and 118 infants in the group with withdrawal within the last week of hospitalization. There were no significant differences in clinical features between the two groups ( P >0.05). Compared with the group with withdrawal before the last week of hospitalization, the group with withdrawal within the last week of hospitalization had a significantly longer duration of the use of caffeine citrate, a significantly shorter length of hospital stay, a significantly lower rate of increased intensity of respiratory support after withdrawal, and a significantly lower incidence rate of moderate or severe bronchopulmonary dysplasia ( P <0.05)., Conclusions: A relatively long course of caffeine citrate treatment is more beneficial to the short-term clinical outcome of very preterm infants.

Objective: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants., Methods: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP., Results: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity ( P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition ( P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group ( P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP ( P < 0.05)., Conclusions: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

Objective: To observe the effect of the meniscus shaping on the knee function and stability after anterior cruciate ligament reconstruction(ACLR)., Methods: A total of 64 ACLR patients were included from January 2013 to January 2015. The control group was the ACLR patients with intact meniscus, in which 24 males and 6 females. The mean age was(32.8±5.5) years old(ranged, 22 to 43 years old). The injury side was left on 17 cases and right on 13 cases. The mean follow-up time was(15.2±2.8) months(ranged, 12 to 19 months). The shaping group was the ACLR patients with meniscus shaping, in which 27 males and 7 females. The mean age was (33.1±4.2) years old (ranged, 23 to 42 years old). The injury side was on the left in 22 case and right in 12 cases. The mean follow-up time was (16.0±3.1) months (ranged, 12 to 20 months). The preoperative anterior tibia shift and knee joint function, as well as anterior tibia shift, knee joint function and active proprioception at last follow-up time were observed. The anterior tibia shift was measured by KT-1000. The knee joint function was assessed by Lysholm score and KOOS score. The errors of active proprioception were measured at 30°, 45° and 60° knee flexion., Results: Postoperative anterior tibia shift of the affected side was (1.4±0.2) mm, which was lower than (2.2±0.4) mm in shaping group( P <0.05). The postoperative total Lysholm scores of the control group and the shaping group were 93.7±2.7 and 92.3±3.0 respectively, which were higher than 52.8±3.9 and 51.6±5.1 preoperatively( P <0.05), but there were no significant differences between two groups( P >0.05). In the KOOS score, the postoperative symptoms, pain, daily life, exercise capacity and life quality in control group were 90.7±5.5, 93.2±4.3, 96.8±2.2, 90.9±5.3, 91.8±4.5 respectively, which were higher than 72.7±6.0, 70.6±7.3, 72.5±7.4, 52.8±5.4, 36.2±6.5 preoperatively( P <0.05); the postoperative symptoms, pain, daily life, exercise capacity and life quality in the shaping group were 88.9±5.8, 92.6±3.5, 96.5±2.1, 89.3±7.2, 90.6±4.1 respectively, which were higher than 71.9±5.1, 71.2±7.1, 71.3±6.2, 53.1±6.1, 35.6±4.7 preoperatively( P <0.05). No significant differences were observed in each postoperative item of KOOS between the two groups( P >0.05). No significant differences were observed in the postoperative active proprioception error of contralateral side between the control group(12.2±3.4)°and shaping group(12.8±3.2)°( P >0.05). The error of active proprioception in the affacted side of the control group was(13.5±3.7)°, which was lower than that in the shaping group(17.1±4.2)°( P <0.05). In control group, there was no significant difference in the active proprioception error between two sides( P >0.05). While in shaping group, the error of active proprioception in the affacted side was significantly greater than that in the contralateral side( P <0.05)., Conclusions: In short and medium term, meniscus shaping has no effect on knee joint function in patients with ACLR, but it impairs the knee proprioception and stability., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Although the function of the anterolateral stabilizing structures of the knee in the anterior cruciate ligament (ACL) injuries has been recognized since many years, most of orthopedic surgeons do not take the anterolateral structure into consideration when performing an ACL reconstruction. Anatomic ACL reconstruction will improve knee stability, but a small subset of patients may experience some residual anteroposterior and rotational instability. For this reason, some researchers have paid attention to the anterolateral aspects of the knee, especially the anterolateral ligament. We don't know the best time to perform ACL and ALL reconstruction. And we lack the evidence to prove which technique is the best one. So we look forward to more random controlled trial., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To compare the clinical effect of Endobutton plates combined with an anchor and clavicle hook plate in the treatment of acromioclavicular dislocation., Methods: From January 2012 to August 2014, 83 patients with Rockwood type III acromioclavicular dislocation underwent surgical treatments. Among them, 34 patients were treated with Endobutton plate and anchor repair(Endobutton group), including 23 males and 11 females, and the mean age was(39.0±6.3) years old (26 to 51 years old); the average time from injury to operation was(4.1±1.3) days(3 to 7 days);the injured side:14 left, 20 right; the dislocation in 28 patients dues to fall, 6 patients dues traffic accident. There were 49 patients treated with clavicular hook plate(hook plate group), including 33 males and 16 females;the mean age was(37.9±6.3) years old (27 to 53 years old); the average time from injury to operation was(4.1±1.1) days (2 to 7 days);the injured side: 18 left, 31 right;the dislication in 36 patients dues to fall, 13 patients dues traffic accidents. The indexes such as intraoperative bleeding volume, operation time, incision size, postoperative complication and postoperative coracoclavicular space, shoulder joint function, and life quality were compared between two groups., Results: In the hook plate group with 49 patients, the plates in 43 patients were removed at the secondary operation, and 32 patients had shoulder pain or limited active range. Thirty four patients in the Endobutton group had no pain symptoms and limited active range. All the patients did not suffer acromioclavicular dislocation again. There was no significant difference between the two groups in operation time, and intraoperative bleeding volume( P >0.05). The incision length in the hook plate group was longer than that in Endobutton group( P <0.05). The coracoclavicular space of the uninjured and injured side in two groups respectively had no significant differences, and the coracoclavicular space in the injured side between two group had no significant difference( P >0.05). There were no significant differences of Constant score and SF-36 between two groups 2 months after operation( P >0.05). Sixteen months after operation, the Constant score in the injured side of both groups was higher than that in 2 months postoperative. But the Constant score in the injured side of hook plate group was higher than that in Endobutton group( P <0.05). The Constant score in the uninjured side had no significant differences between two group( P >0.05). In hook plate group, the Constant score in the uninjured side was higher than that in the injured side. In Endobutton group, there were no significant differences of Constant score between two sides. The 16 month postoperative SF-36 in the injured side of both groups was higher than the 2 month postoperative one, but 16 month postoperative SF-36 in hook plate group was lower than that in Endobutton group ( P <0.05)., Conclusions: Endobutton plate combined with an anchor can effectively fix Rockwood type III or more acute acromioclavicular dislocation. The method has less complications, avoiding secondary removal of internal fixation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Objective: To compare clinical outcomes of superior labrum from anterior to posterior (SLAP) repair and biceps tenodesis in treating type I SLAP injury., Methods: From March 2009 to March 2012, 38 patients with type II SLAP injury were treated with SLAP repair and biceps tenodesis, and all patients were unilateral SLAP injury. Sixteen patients treated with biceps tenodesis included 8 males and 7 females with an average age of (49.3±3.7) years old (ranged, 45 to 54); 10 cases were on the left side and 6 cases on the right side; 10 cases were caused by falling down, 2 cases were caused by throwing damage and 4 cases were caused by daily life damage; the time from injury to operation were from 3 to 8 weeks. Twenty-two patients treated with SLAP repair included 14 males and 8 females with an average age of (49.0±2.8) years old (ranged, 44 to 56); 13 cases were on the left side and 9 cases were on the right side; 14 cases were caused by falling down, 5 cases were caused by throwing damage and 3 cases were caused by daily life damage; the time from injury to operation were from 3 to 7 weeks. Preoperative, postoperative at 6 months, 1 year and 2 years' UCLA and SST score were compared between two groups., Results: There was no significant differences in UCLA and SST score between two groups before operation. At 6 months after operation, UCLA and SST score in biceps tenodesis group was higher than SLAP group, and action,range of anteflexion, strength of anteflexion, degree of satisfaction in biceps tenodesis group was higher than SLAP group. There was no significant meaning in SST and UCLA score between two groups at 1 and 2 years after operation., Conclusion: Short-term efficacy of biceps tenodesis for SLAP injury is better than SLAP repair, but long-term efficacy is fairly.

Objective: To explore the effects of statins upon bone mineral density (BMD) and bone metabolic markers in postmenopausal women with hypercholesterolemia., Methods: A prospective study was conducted for 100 women receiving treatment from January 2011 to August 2012 and meeting the inclusion criteria of osteopenia or osteoporosis with hypercholesterolemia postmenopausal. They were randomly divided into treatment group on atorvastatin 10 mg once daily and control group. The parameters of lumbar BMD, bone resorption markers of type I collagen cross-linked C-telopeptide (CTX) , bone synthesis markers procollagen type I N-terminal peptide (PINP) were compared between two groups after half a year and one year., Results: There was an upward trend of lumbar spine BMD and PINP in the treatment group at half a year and one year compared with the control group. And two groups had significant difference (P < 0.05). Although two groups had no significant difference in all parameters at half a year, the values of lumbar spine BMD and PINP were higher in the treatment group at one year than the control group. Two groups had significant difference (P < 0.05)., Conclusions: Statins can help maintain or increase bone mass of hypercholesterolemic menopausal women through promoting bone synthesis.

Objective: To investigate the effects of microRNA-383 (miR-383) on PRDX3 gene expression, cell proliferation and apoptosis of human medulloblastma., Methods: PRDX3 and miR-383 RNA expression was detected by real-time quantitative RT-PCR in human medulloblastoma tumor tissue samples, Daoy cell line and normal brain tissue samples. Western blot was used to detect protein expression of PRDX3. Synthetic miR-383 mimics were transfected into Daoy cells by lipofectamine. Using Cell Counting Kit-8 (CCK-8) method, flow cytometry was used to investigate the cell proliferation and apoptosis, cells reactive oxgen species(ROS), mitochondrial membrane potential changes in each experimental groups., Results: Of 15 cases of human medulloblastoma tumor, 13 cases had miR-383 expression levels significantly lower than that of normal brain tissue, and 14 had PRDX3 mRNA expression levels significantly higher than that of normal brain tissue. The expression levels of miR-383 and PRDX3 in Daoy cells were 0.353 and 1.315 times than those of normal brain tissue, respectively. The protein expression levels of PRDX3 were higher in human medulloblatoma tumors and Daoy cells than that of normal brain tissue. Transfected miR-383 mimics increased the expression level of miR-383 after 24 h and 48 h was significantly higher than that of the control. In contrast, PRDX3 gene mRNA and protein expression levels were significantly decreased at 48 h compared with the control group. Using CCK-8 assay, the cell proliferation rate in the experimental group was significantly lower than that of the control group (P < 0.05). Annexin V-FITC assay demonstrated that early apoptosis rate of the experimental group (11.60 ± 0.30)% was significantly higher than those of the control group (2.3 ± 0.20)% and negative control group (10.37 ± 0.25)% (P = 0.000) after 48 h of transfection. The intracellular ROS levels after transfection at 24 and 48 h significantly increased than those of the control group. Mitochondrial membrane potential level at 24 h after transfection significantly decreased, comparing with the blank control group and the negative control group., Conclusions: Compared with normal brain tissue, decreased expression of miR-383 but elevated expression of PRDX3 are medulloblastoma tumour and Daoy cell lines. Up-regulation of miR-383 knockdowns the expression of PRDX3, inhibits proliferation and promotes apoptosis of Daoy cells, leading to increased intracellular ROS and decreased levels of mitochondrial membrane potential.

Objective: To explore the effect of microRNA-21 (miR-21) antisense oligonucleotide on the biological characteristics of human cervical squamous carcinoma cell lines SiHa in vivo and in vitro., Methods: Specific phosphorothioate antisense oligodeoxynucleotides targeting miR-21 were synthesized and transfected into cervical cancer cells in vitro. Expression of miR-21 in SiHa after transfection was detected by real-time RT-PCR. The cell proliferation was evaluated by MTT assay and colony formation experiment. The cell apoptosis was analyzed by annexin V-FITC/PI analysis. The inhibitory effect of miR-21 antisense oligonucleotide on tumor growth was evaluated by tumor growth curves and immunohistochemistry (MaxVision method). H-E staining was used to document morphological changes and fluorometric TUNEL assay was to detect the apoptotic activity., Results: After the transfection of antisense miR-21, the expression of miR-21 decreased along with an obvious growth inhibition, compared with that of the control groups (P < 0.05). Colony formation of both cell lines was markedly inhibited with antisense miR-21 (55.6% ± 1.4%), as compared with that in the negative group (98.3% ± 2.0%, P < 0.05). Flow cytometry assay showed that antisense miR-21 expression significantly enhanced the cell apoptosis (6.7% ± 1.3% and 29.4% ± 1.7%, P < 0.05). The tumor-forming rates of miR-21 transfected group, and negative control groups were 3/8 and 6/8, respectively (P < 0.05). Ki-67 proliferative marker staining decreased significantly (42% vs 90%) in the transfected group compared with negative control groups. Extensive dead tumor cells were seen in the miR-21 transfected cells along with a marked increase of apoptosis (P < 0.05)., Conclusion: Targeted antisense oligonucleotide miR-21 effectively suppresses the growth of cervical carcinoma SiHa cells both in vitro and in vivo through an induction of apoptosis.

Objective: To study the effect of L-arginine (L-Arg) on Pax2 expression in the kidneys of pup rats with intrauterine growth retardation (IUGR)., Methods: Pregnant rats were randomly assigned into three groups：normal, IUGR and L-Arg treated IUGR. The rats in the normal group were fed with ordinary forage (21% protein) during pregnancy. Those in the other two groups were fed with low diet forage (10% protein) during pregnancy. The L-Arg treated group was given drinking water containing L-Arg (200 mg/kg) daily during 21 days of lactation. Pax2 expression in renal tissues was measured with immunohistochemical staining and Western blot in pup rats of 7 days, 21 days, 2 months and 3 months old., Results: The immunohistochemical staining showed that Pax2 was not expressed in the pup rats from the normal group at any time point. Pax2 positive cells were found in renal glomerulus and kidney tubules of 2-months- and 3-months-old rats from the IUGR and L-Arg treated groups. And Pax2 expression in 3-months-old rats was significantly higher than that in 2-months-old rats (P<0.05). L-Arg treatment decreased significantly the Pax2 expression in 2-months- and 3-months-old rats when compared with the untreated IUGR group (P<0.05). Western blot showed that Pax2 protein was not expressed in 7-days- and 21-days-old pup rats from three groups. Pax2 protein expression in 2-months- and 3-months-old pup rats from the IUGR and L-Arg treated groups increased significantly compared with normal controls. Pax2 protein expression in the pup rats from the L-Arg treated group was significantly lower than that in the untreated IUGR pup rats (P<0.01)., Conclusions: Pax2 is expressed in the kidneys of IUGR rats during adulthood. L-Arg treatment can decrease the expression of Pax2.

Objective: To evaluate the efficacy and safety of ganciclovir therapy for congenital cytomegalovirus (CMV) infection in newborn infants., Methods: The randomized controlled trials (RCTs) and quasi-RCTs on ganciclovir therapy for congenital CMV were reviewed in the following electronic databases: PubMed (January 1988 to January 2009), EMbase (January 1988 to January 2009), the Cochrane library (Issue 3, 2003 and Issue 1, 2009), the Chinese Journals Full-text Database (January 1994 to January 2009), the Chinese Biological Medical Disc (January 1994 to January 2009) and the Chinese Medical Current Contents (January 1994 to January 2009). Quality assessment, data extraction, and meta analysis were performed., Results: Ten papers were included. Meta analysis showed that the ganciclovir therapy increased the improvement rate (91.4% vs 34.0%; p<0.01) and led CMV infection indexes to become negative in more patients (87.6% vs 15.3%; p<0.01) and decreased incidence of hearing disturbance (4.7% vs 37.2%; p<0.01) as compared with the non-ganciclovir therapy control group. The incidence of the ganciclovir-therapy-related side effects was low., Conclusions: Ganciclovir treatment may increase the improvement rate and the rate of CMV infection indexes becoming negative, and decrease incidence of hearing disturbance, with few side effects, in newborn infants with CMV infection. However the supporting evidence is not strong due to few trials and more high-quality research is needed.

Objective: Ganciclovir is a first-line drug for treatment of cytomegalovirus (CMV) infection. However, some ganciclovir treatment-related side-effects can be found. This study aimed to compare the efficacy and side effects of relatively low and high doses of ganciclovir in the treatment of neonatal congenital CMV infection., Methods: One hundred and sixty-seven neonates with congenital CMV infection were randomly assigned to high-dose (n=79) and low-dose ganciclovir groups (n=88). The high-dose ganciclovir group was injected with ganciclovir of 7.5 mg/kg in the inducement phase and of 10 mg/kg in the maintaining phase. The low-dose ganciclovir group was injected with ganciclovir of 5 mg/kg in the inducement and the maintaining phases. The efficacy and side effects were observed in the two groups., Results: After treatment the clinical symptoms and signs were obviously improved in both groups. CMV-IgM became negative in 93.8% of neonates in the high-dose ganciclovir group and 93.1% of neonates in the low-dose ganciclovir group (P>0.05). CMV-DNA became negative in 80.8% of neonates in the high-dose ganciclovir group and in 86.7% in the low-dose ganciclovir group (P>0.05). The low-dose ganciclovir group had lower incidence of side effects than the high-dose ganciclovir group: vomiting 2.3% vs 11.4%; anemia 8.0% vs 20.3%; reduction of neutrophilic granulocytes 5.7% vs 16.5%; increase in platelet count 8.0% vs 18.9% (P<0.05)., Conclusions: Low-dose ganciclovir has the same clinical efficacy to high-dose ganciclovir for treatment of neonatal congenital CMV infection, but fewer side effects occur in the low-dose group.

Objective: To investigate the prevalence of snoring in school age children from Changsha City, and study the correlation of snoring with attention deficit and hyperactivity-impulsivity., Methods: A total of 1 736 children aged 6 to 12 years were randomly sampled from five districts in Changsha City. Their parents completed the questionnaires about children's sleep conditions and the Attention Deficit Hyperactivity Disorder Diagnostic Scale-Parent Version., Results: The total incidence rate of frequent snoring was 5.7%. Boys had higher incidence of frequent snoring than girls (7.5% vs 3.8%; x2=18.782, p<0.01). The incidence of snoring in the 6-to 9-year-old group was higher than that of the 10-to 12-year-old group (x2=9.666, P<0.01). The incidence of daytime sleepiness in the snoring group was higher than that in the non-snoring group (31.5% vs 25.9%; x2=6.678, p<0.01). The incidences of larynx choking, sleep apnea, mouth breathing, hyperhidrosis, and awaking for unknown reasons or awaking by choke in the frequent snoring group were significantly higher than in the occasional snoring and the non-snoring groups (x2=37.035, 27.745, 51.341, 30.975, 45.972 respectively; all P<0.01). The incidences of attention deficit (31.3%) and hyperactivity-impulsivity (18.2%) in the frequent snoring group were the highest, followed by the occasional snoring (16.2% and 9.9% respectively) and the non-snoring groups (13.9% and 8.8% respectively). There were significant differences in the incidence of both attention deficit (x2=20.592, p<0.01) and hyperactivity-impulsivity (x2=9.067, p<0.05) between groups., Conclusions: There is a high incidence of snoring in school age children from Changsha City. Snoring is correlated to attention deficit and hyperactivity-impulsivity. It is essential to pay attention to the mental growth and behavioral problems in children with sleep snoring.