Background The compound 6:2 chlorinated polyfluorinated ether sulfonic acids (6:2 Cl-PFESA) has been demonstrated abilities of strong bioaccumulation and placental barrier penetration, and it can also cross the blood-brain barrier. However, the mechanism of its neurodevelopmental toxicity in offspring induced by early-life exposure is still unknown. Objective To explore effects of 6:2 Cl-PFESA on the growth and the α-amino-3-hydroxy-5-methylisoxazole-4-propionic (AMPA) receptor gene expression in the hippocampus of offspring mice by establishing a 6:2 Cl-PFESA exposure animal model. Methods Thirty Kunming pregnant mice were randomly divided into five groups: control group, and 2, 10, 50, and 250 μg·L⁻¹ 6:2 Cl-PFESA exposure groups. The treatment groups were exposed to designed doses of 6:2 Cl-PFESA through drinking water from the first day of gestation until the end of lactation. The pups were weaned on postnatal day (PND) 21, and continued to be exposed to 6:2 Cl-PFESA through drinking water. Birth weight and body length of the offspring were recorded. Offspring mice were anesthetized and sacrificed respectively on PND7, PND21, and PND35, then their hippocampus was peeled from harvested brain tissue. The ultrastructure of hippocampus was observed via transmission electron microscopy; and the expression of AMPA receptors GluR1, GluR2, and GluR3 in the hippocampus was evaluated by real-time reverse transcription polymerase chain reaction. The learning and memory ability of the PND35 mice was measured by Morris water maze test before they were sacrificed. Results The birth weights and the lengths of the pups in the 10, 50, and 250 μg·L⁻¹ 6:2 Cl-PFESA exposure groups were (2.23±0.36), (1.92±0.20), (1.88±0.31) g, and (33.73±0.98), (32.91±1.30), (32.52±2.07) mm, respectively, which were lower than those in the control group, (2.78±0.35) g and (36.46±2.34) mm (P<0.05), respectively. The results of Morris water maze showed that the escape latencies in the orientation navigation experiment on the 4th day in the 250 μg·L⁻¹ 6:2 Cl-PFESA exposure group and on the 5th day in the 10, 50, and 250 μg·L⁻¹ 6:2 Cl-PFESA exposure groups were longer than those in the control group (P<0.05). In the space exploration experiment, the times of crossing platform in the 50 and 250 μg·L⁻¹ 6:2 Cl-PFESA exposure groups were decreased when compared with the control group (P<0.05), and the time of staying in the target quadrant of the 250 μg·L⁻¹ 6:2 Cl-PFESA exposure groups were also decreased (P<0.05). Via transmission electron microscopy, compared with the control group, the postsynaptic density was decreased and the synaptic cleft width was widened on PND35 in the 250 μg·L⁻¹ 6:2 Cl-PFESA exposure group. The mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups exposed to 250 μg·L⁻¹ 6:2 Cl-PFESA during different developmental stages were significantly lower than those in the control group (P<0.05). Except for the 2 μg·L⁻¹ 6:2 Cl-PFESA exposure group on PND7, the 6:2 Cl-PFESA exposure inhibited the mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups at different developmental stages (P<0.05). Among them, the 6:2 Cl-PFESA exposure during early development resulted in the highest decrease in the expression levels of GluR1 and GluR2 mRNA in the hippocampus of pups on PND7; GluR3 mRNA expression level in the hippocampus of the exposed pups on PND21 showed the maximum inhibitory effect; the expression levels of GluR1, GluR2, and GluR3 mRNA all showed the least decrease in the hippocampus of the exposure groups on PND35. Conclusion Early-life exposure to 6:2 Cl-PFESA may affect the growth and development of offspring mice, alter the hippocampal synaptic structure, and influence the learning and memory abilities, which may be related to their inhibitory effects on the expression levels of AMPA receptor subunits GluR1, GluR2, and GluR3 genes in the hippocampus of offspring mice at various developmental stages.

Objective:To assess the efficacy of a minimally invasive technique for repairing tibial plateau bicondylar fractures utilizing the double reverse traction repositor.Methods:A retrospective analysis was performed of the data of 31 patients (Schatzker V 17 cases, Schatzker VI 14 cases) who had been admitted to trauma center of Shandong provincial hospital affiliated to Shandong first medical university for tibial plateau bicondylar fractures from January 2017 to January 2022. There were 21 males and 10 females, aged from 18 to 67 years (average, 32.4±6.5 years). The intervention strategy comprised the use of a double reverse traction repositor and was augmented by precise screw fixation. A comprehensive set of parameters were measured, including time interval between injury and operation, operation time, blood loss, hospital stay, fracture healing time, incision complications. Postoperative assessments were made immediately and at the 12-month mark, including the evaluation of articular step-off height, medial tibial plateau angle, and posterior tibial slope angle. The evaluation also included thTime interval between injury and operation ranged from 5 to 11 days, with an average of 6.1±1.3 days. The surgical procedures varied in length from 70 to 160 minutes, averaging at 109.2±15.6 minutes. The volume of blood loss was noted to be between 90 to 380 ml, averaging at 176.5±20.8 ml. Hospitalization spanned from 10 to 15 days, with an average stay of 12.2 ±0.8 days. Over a follow-up duration of 12 to 20 months, averaging at 13.5±1.1 months, all patients achieved fracture union within a period of 11 to 20 weeks, with an average time of 14.6±1.5 weeks. The postoperative articular step-off was recorded at 0.45±0.13 mm immediately after surgery and 0.58±0.21 mm at the one-year follow-up. Similarly, the medial tibial plateau angle and posterior tibial slope angle showed marginal changes from the immediate postoperative period to the 12-month evaluation. Knee joint mobility at the one-year mark ranged impressively from 0° to 135°, with an average of 125.6°±2.1°. Functional outcomes as reflected by Rasmussen scores ranged from 18 to 28 points, with an average of 25.4±1.7 points. Pain, as assessed by the VAS, had a low score range of 0 to 2 points, averaging at 0.7±0.2 points. Notably, there were no postoperative complications associated with the incisions, such as fat liquefaction, infection, skin necrosis, or exposure of internal fixations. Additionally, no cases of delayed union or fixation failure were observed. Six patients had traumatic arthritis 1 year after operation.Conclusion:The minimally invasive double reverse traction repositor technique for tibial plateau bicondylar fracture repair is effective, warranting its broader application in orthopedic surgery.

OBJECTIVE To establish a method for simultan eous determination of 5 kinds of pentacyclic triterpenoids as 3-O- acetyl-pomolic acid in Chaenomeles speciosa ，and to analyze the difference in the contents of C. speciosa from different producing areas by different processing technologies . METHODS HPLC method was adopted . The determination was performed on COSMOSIL 5 C18-MS-Ⅱ column with mobile phase consisted of acetonitrile -0.005 mol/L ammonium dihydrogen phosphate solution （pH value adjusted to 6.5 with phosphoric acid ）（70∶30，V/V）at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 210 nm，and sample size was 20 μL. The contents of the other four pentacyclic triterpenoids were calculated according to quantitative analysis of multi -components by single -marker（QAMS）using oleanolic acid as internal reference . The results were compared with those determined by external standard method . The total content of oleanolic acid and ursolic acid ，the total content of 5 components in C. speciosa from different producing areas and different processing technologies were compared . RESULTS The linear range of 3-O-acetyl-pomolic acid ，betulinic acid ，oleanolic acid ，ursolic acid and 3-O-acetyl ursolic acid were 4.06-81.2，2.12-42.4，9.62-192.3，7.77-155.4，4.21-84.1 μg/mL，respectively（R2＞0.999）. RSDs of precision ，reproducibility and stability （24 h）tests were all lower than 3%. The average recoveries were 98.29%-101.38% （RSDs＜3%，n＝6）. The mass fraction of 3-O-acetyl-pomolic acid ，betulinic acid ，ursolic acid and 3-O-acetyl ursolic acid measured by QAMS w ere 0.023%-0.060%，0.044%-0.528%，0.101%-0.368%，0.067%-0.221%，respectively；the deviations from the results measured by external standard method were all within 8%. The total content of oleanolic acid and ursolic acid， the total content of 5 components in C. speciosa processed by fresh -cut technology from the same producing area were higher than those in C. speciosa processed by traditional technology ，and the total content of 5 components in C. speciosa from Chongqing Qianjiang were significantly higher than those from other producing areas （P＜0.05）. CONCLUSIONS QAMS method is established for the simultaneous determination of 3-O-acetyl-pomolic acid ，betulinic acid ，oleanolic acid ，ursolic acid and 3-O-acetyl ursolic acid in C. speciosa. Established method is simple ，rapid and accurate . The total content of 5 components in C. speciosa produced in Chongqing Qianjiang is higher ，and the total content of C. speciosa processed by fresh -cut technology from the same origin is higher than C. speciosa processed by traditional technology .

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

AIM: To explore the effect of Huatanjiangqi capsule medicated serum (HTJQ) on the resistance of human bronchial epithelial cells (16HBE) to glucocorticoid (GC) stimulated by cigarette smoke extract (CSE). METHODS: After 16HBE cells were treated with HTJQ, the effects of different concentrations of HTJQ on the viability of 16HBE cells were determined by CCK-8 method. 16HBE cells were pretreated with HTJQ, and then cultured with dexamethasone (DEX) and lipopolysaccharide (LPS) for 24 hours, the effect of HTJQ on glucocorticoid (GC) resistance of 16HBE cells was determined by Enzyme-linked immunosorbent assay (ELISA). The effects of HTJQ, sulforaphane (SFN) and glutathione (GSH) on the expression of NF-E2-related factors 2 (Nrf2), Heme oxygenase-1 (HO-1) and histone deacetylase 2 (HDAC2) in 16HBE cells stimulated by CSE were measured by Western blot, and the effects of HTJQ, SFN and GSH on interleukin-8 (IL-8) in 16HBE cells were measured by ELISA. RESULTS: HTJQ promoted the proliferation of 16HBE cells at 1 h, 2 h and 4 h, the results of ELISA and Western blot showed that CSE induced GC resistance and decreased the expression of Nrf2, HO-1 and HDAC2 in 16HBE cells, HTJQ significantly decreased IL-8 and improved GC sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). In addition, HTJQ significantly up-regulated the level of GSH in 16HBE cells (P<0.01). Nrf2 agonists SFN and GSH significantly improved the glucocorticoid sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). CONCLUSION: HTJQ improves the GC resistance of 16HBE cells by up-regulating the expression of Nrf2/HDAC2 protein and the level of intracellular GSH.

OBJECTIVE： To rapidly identify chemical components of Zhitong huazheng capsules （shorted for “ZTHZC”）， and to provide reference for further elucidating the pharmacodynamic material basis and overall quality control. METHODS： UPLC-Q-TOF/MS method was adopted to separate the chemical components of ZTHZC. By reviewing literatures that related to chemical components of ZTHZC and its single Chinese traditional medicinal crops， the chemical structure of the chemical components was saved into a .mol format file， and supplemented the UNIFI database. The chemical constituents of ZTHZC were qualitatively analyzed by UNIFI database screening， and validated according to their precise molecular mass， characteristic ions， neutral loss， secondary mass spectrometry cleavage， chromatographic retention behavior， combined reference information and literature reports. RESULTS： A total of 70 chemical components were identified in this experiment， including 38 organic acids and organic acid esters， 8 alkaloids， 9 flavonoids， 5 triterpenoid saponins， 5 aldehydes， 2 ketones， 1 quinone， 1 polyacetylene and 1 monoterpenoid. CONCLUSIONS： This study provides a rapid detection and identification method for chemical components of ZTHZC， and also provides a scientific basis for the clarification of ZTHZC’s quality control and pharmacodynamics.

Objective To investigate the clinical efficacy of tibiocalcaneal arthrodesis using bone transport technique in the treatment of traumatic talus infection or loss. Methods A retrospective case series study was conducted to analyze the clinical data of 15 patients with talus infection or loss admitted to the provincial hospital affiliated to Shandong University from June 2011 to October 2017. There were 13 males and two females, aged from 19 to 47 years, with an average age of 27 years. Thirteen patients had talus infection and two patients had talus loss. All patients underwent tibiocalcaneal fusion with external fixator using bone transport technique, including four patients treated with annular external fixator and 11 with unilateral external fixator. Six patients with severe infection underwent debridement at stage I and osteotomy at stage II, and the other nine underwent debridement and osteotomy at the same time. The length of new bone, the fixation time of external fixator and complications were recorded. The American Orthopedic Foot and Ankle Society ( AOFAS ) score was used to evaluate the efficacy. Results All patients were followed up for 18-35 months, with an average of 26 months. The length of new bone in proximal tibial osteotomy area was 5-16 cm, with an average of 9 cm. The external fixators were removed after bone healing at docking site and maturation of new bone. The fixation time of external fixator ranged from 13 to 27 months, with an average of 18 months. No complications such as needle breakage, recurrence of infection and calcaneal varus occurred, and the length of both lower limbs was equal. AOFAS score was increased from preoperative (42. 0 ± 3. 6)points (31-55 points) to (76. 0 ± 4. 2)points (69-86 points ) at the last follow-up. Conclusion Tibiocalcaneal arthrodesis using bone transport technique is proved to be effective in treating traumatic talus infection or loss, which can repair the bone defect after debridement, improve the ankle-hindfoot function and improve the quality of life.

Objective To explore the characteristics of calcifying pseudoneoplasm of the neuraxis ( CAPNON) , and to improve the di-agnostic level and standard of treatment. Methods The clinical traits, imaging features and curative effect of one case of CAPNON who were treated in our departmen were analyzed combined with the pathological analysis and literature review. Results Transient back pain was the only clinical presentation of the patient. CT images showed obvious calcification. MRI showed low signal in T1-weigthed images and T2-weighted images. Examined with the contrast-enhanced MR images, the lesion showed inhomogeneous enhancement. No nervous symptom newly occurred in the 6-month follow-up. Conclusion Symptoms of patients with CAPNON are generally related to local compression or irri-tation of the adjacent tissue. CAPNON should be highly suspected in patients with dense calcification in the CT combined with low signal in T1-weigthed images and T2-weighted images and rim or internal inhomogeneous linear enhancement in the MRI. The final diagnosis depends on the histopathological analysis, and surgical resection is the major therapy.

Objective To evaluate the incidence,severity,risk tactors and impact to prognosis of acute kidney injury (AKI) in patients with severe traumatic brain injury (sTBI) by using acute kidney injury network (AKIN) classification system.Methods A retrospective analysis was carried out in 136 patients with sTBI hospitalized between January 2007 and May 2011.Demographic data,admission evaluation (whether with hernia or not on admission,systolic pressure and mean arterial blood pressure,serum creatinine and urea nitrogen,and blood glucose),outcome at 6 months post-injury and mortality were collected.Renal function was assessed using AKIN criteria.The patients were divided into two groups based on the presence or absence of AKI (non-AKI group and AKI group).According to the severity of AKI,AKI group was further classified as AKI grade 1 group,AKI grade 2 group and AKI grade 3 group.The differences among groups were analyzed.Results According to AKIN classification system,31 (23％) out of the 136 patients were diagnosed as being with AKI,including 21 cases (68％) in AKI grade 1 group and 10 cases (32％) in AKI grade 2 and 3 groups.The patients at older age and with lower Glasgow coma scale (GCS) on admission,higher levels of serum creatinine and blood urea nitrogen on admission were prone to AKI.As compared with TBI patients with normal renal function,TBI patients associated with AKI had higher mortality and worse outcome.Conclusions AKI is a common complication of patients with sTBI.AKIN classification system can early diagnose AKI in sTBI patients and may contribute to improvement of the outcome.