Objective To observe the changes of neutrophil gelatinase associated lipocalin,NGAL after endoplasmic reticulum stress by thapsigargin in renal tubular epithelial cells.Methods The renal tubular epithelial cells were treated with thapsigargin to establish the model of endoplasmic reticulum stress (ER group).CHOP and GRP78 expression were detected by Western-blot to confirm endoplasmic reticulum stress in renal tubular epithelial cells by thapsigargin.NGAL expression were detected by Western-blot in ER group and control group(normal renal tubular epithelial cells).Results After treated with 2.5 μmol/L and 5 μmol/L thapsigargin for 4 hours and 8 hours respectively,endoplasmic reticulum stress in the renal tubular epithelial cells were significantly increased comparing with control group (0.585 ± 0.045 to 0.523 ± 0.030;0.785 ± 0.049 to 0.728 ± 0.064),which was approved by the increased expression of CHOP and GRP78 (P ＜ 0.05).The expression of NGAL was significantly increased in ER group (0.567 ± 0.024 to 0.826 ± 0.057,P ＜ 0.05) and it was corresponded with the changes of CHOP and GRP78,which increased significantly with the severity of endoplasmic reticulum stress.Conclusion Endoplasmic reticulum stress can be induced by thapsigargin in renal tubular epithelial cells.The expression of CHOP,GRP78 and NGAL were significantly increased correspondingly with the severity of endoplasmic reticulum stress.It is speculated that the expression of NGAL may be related with endoplasmic reticulum stress in tubular epithelial cells.

Objective:To investigate the clinical significance and possible mechanisms of elevated homocysteine(Hcy) levels in peripheral blood of children with sepsis.Methods:The clinical data of 51 children with sepsis (sepsis group) admitted to PICU at Xuzhou Children′s Hospital from January 2019 to December 2019 were analyzed, and the levels of Hcy in plasma were compared with 50 non-septic children (common infection group) and 50 healthy children (healthy control group) during the same period.The possible mechanism of metabolic disorders about Hcy was analyzed by detecting the levels of the key rate-limiting enzymes cystathionine-β-synthase(CBS) and cystathionine-γ-lyase(CSE), which were in the downstream of metabolism in septic mouse model induced by lipopolysaccharide.Results:The level of Hcy in plasma was (12.62±5.46)μmol/L in sepsis group, which was significantly higher than those in common infection group[(9.42±2.28) μmol/L] and healthy control group[(8.14±1.60) μmol/L]( P<0.05). The level of Hcy in plasma of 12 children with acute kidney injury in sepsis group was significantly higher than that of 39 children without acute kidney injury in sepsis group[(16.48±5.87)μmol/L vs.(11.62±4.74) μmol/L, P<0.05]. The level of Hcy in plasma of six children with acute liver failure in sepsis group was significant higher than that of 45 children without acute liver failure in sepsis group[(18.35±7.10) μmol/L vs.(11.84±4.78) μmol/L, P<0.05]. The level of Hcy in serum significantly increased in septic mouse models ( P<0.01). The transcription and protein expression levels of key rate-limiting Hcy transcription enzymes CBS and CSE in liver and kidney tissues of septic mouse were significantly down-regulated ( P<0.05). Conclusion:The level of Hcy in peripheral blood of children with sepsis increases, which is more obviously in children with acute kidney injury or acute liver injury.When patients developed sepsis, the expression of CBS and CSE will be restrained, leading to disorders related to transsulfuration metabolism and elevated level of Hcy in peripheral blood.

Objective To investigate the dynamic mechanical responses and damage characteristics of peri-implant bone structures subjected to impact load.Methods A finite element model of the peri-implant bone microstructure was established,and an initial velocity was applied to the rigid body to simulate the impact load.A stress failure criterion was employed and a user-material subroutine was developed to assess failure.Subsequently,bone damage after the impact load was analyzed according to the material subroutine.Results After the impact load,the stress on the cortical bone increased rapidly,reaching a peak value(16.01 MPa)immediately.In contrast,the stress on the trabecular bone at the bottom of the implant reached its peak value(5.85 MPa)at 0.1 μs.The impact load resulted in stress waves that propagated and diffused within the bone structure,causing changes in the bone structure damage over time.The generated impact energy could be absorbed and dissipated by the trabecular bone through deformation.The deformed trabecular bone experienced damage and failure upon reaching the yield limit,whereas the cortical bone did not experience damage or failure under an impact load.Conclusions Structural changes in the trabecular bone should be considered in patients with impact damage.The numerical model established in this study can effectively predict bone impact damage by combining the structural mechanical properties and geometric characteristics of the bones.These findings can serve as a reference for assessing bone damage and post-damage treatment in patients subjected to impact loads in clinical practice.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.