Objective: To investigate the effects of culture medium osmolarity on the proliferation of human hepatoma cell line HHCC. Methods:Cell proliferation was analyzed by MTT assay and cell cycle analysis was carried out by flow cytometry. Results:Hyperosmolarity decreased significantly the absorbance (A) of HHCC cells and cell number, and hyposmolarity have counter effects. Compared with control, hyperosmolarity blocked cell cycle progression at the G 1 phase, while hyposmolarity accelerated cells into S phase from G 1 phase, and the effect of hyposmolarity was weakened by chloride channel blocker NFA. Conclusion:Culture medium osmolarity influenced the proliferation of HHCC cells by mediating cell cycle.

Objective To investigate the effects of sodium butyrate on the activity of RAW264.7 cells and the osteoclast differentiation.Methods The RAW264.7 cells were treated by sodium butyrate at concentrations of 0,0.25,0.50,1.00,2.00,3.00,4.00 and 5.00 mmol/L,with 3 double pores for each concentration.The cytotoxicity of sodium butyrate on RAW264.7 cells was detected by a CCK-8 kit.The effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on apoptosis of RAW264.7 cells were detected by Hoechst33342 staining.RAW264.7 cells were induced into osteoclasts by osteoclast differentiation factors.The experiment was carried out in 2 groups (n =3).After induced maturation,the experimental group was treated with 1.00 mmol/L sodium butyrate and the control medium was added only with the same volume of solvent.The number of osteoclasts and the area of bone resorption were observed and compared.The differentiation of RAW264.7 cells was detected by tartrate-resistant acid phosphatase (TRAP) staining.Western blotting was used to detect the effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on NF-κB-related signaling pathway in RAW264.7 cells.Results Compared with the group of 0 mmol/L sodium butyrate,the activity of cells treated with 1.00,2.00,3.00,4.00 and 5.00 mmol/L sodium butyrate for 24 h was significantly decreased (P ＜ 0.05).Treatment with 1.00 mmol/L sodium butyrate for 24 h induced apoptosis.The number of osteoclasts in the control group and the experimental group were 9.33 ± 2.08 and 4.67 ± 1.16,respectively,showing a significant difference between the 2 groups (t =3.395,P =0.027).The percentages of bone resorption area in the control group and the experimental group were 52.43％ ± 5.38％ and 14.28％ ± 2.72％,respectively,also showing a significant difference between the 2 groups (t =10.970,P ＜ 0.001).Western blot results showed that,compared with other concentrations of sodium butyrate,treatment with 1 mmol/L sodium butyrate on RAW264.7 cells for 24 h led to an increase in the expression levels of cytoplasmic p65,B lymphoma-2 associated X protein and cleaved-caspase 3 and the acetylation of Histone H3 but a decrease in the phosphorylation level of α/β subunit of NF-κB kinase.Conclusions With the increased concentration of sodium butyratecan,the activity of NF-κB may be suppressed and the number of apoptotic cells may increase.1.00 mmol/L sodium butyrate can reduce osteoclast formation and bone resorption area.

As one of the major body fluid, saliva has various components that can shift according to the systemic health state. With the atraumatic way of collection, saliva can be a promising media to help the detection of oral diseases. With the development of salivaomics and the application of unbiased, highly sensitive, and high throughout separation techniques for salivary components, there′s now more possibilities for effective identification of biomarkers correlated with oral diseases. This review aimed to introduce the current state of saliva collection and detection techniques as well as their correlation with oral diseases, hoping to provide evidence for further research.

BACKGROUND:As a bone replacement and filling material,calcium phosphate stone bone cement has good biocompatibility,bone conductivity,and other advantages,especially its better biodegradability compared to other calcium phosphate bone cements.It has important application value in bone repair.However,due to its limitations such as insufficient mechanical properties,fast solidification reaction,and poor injection performance,it is currently only suitable for the repair of non weight-bearing bone. OBJECTIVE:To explore the modification of brushite cements with bioactive ions(metal and non metal ions)to expand its application range. METHODS:The author used PubMed,ScienceDirect,CNKI,and WanFang to search the literature published between 2018 and 2023 with the search terms"metal ion,iron,copper,strontium,magnesium,zinc,non-metal ion,modification,bone,brushite cements"in Chinese and"metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,brushite cements"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant and duplicate articles were excluded.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Bioactive ions affect the hydration process of calcium phosphate bone cement.Different ions are substituted by ions and incorporated into the crystal structure of calcium phosphate bone cement,changing the crystal morphology of the cement and causing changes in physical and chemical properties such as setting time,injectability,and compressive strength.(2)Ionic modified calcium phosphate bone cement produces different ion release effects due to different crystal structures.Different types of ions have properties such as promoting angiogenesis/osteogenesis,antibacterial,anti-tumor,etc.In addition,calcium phosphate bone cement has good biodegradability,which has great advantages for the performance of various ions.(3)The physicochemical properties of calcium phosphate bone cement modified with different ions are as follows:iron,copper,strontium,magnesium,zinc,silver,and cobalt can prolong the setting time.Strontium,and magnesium can improve injection performance.Copper,strontium,magnesium,silver and silicon can enhance compressive strength.The ions that can simultaneously improve the three physical and chemical properties of calcium phosphate bone cement include strontium and magnesium.Good physical and chemical properties are a prerequisite for clinical application,so improving the setting time,injectability,compressive strength,and other properties of calcium phosphate bone cement with ions is of great significance for the research and application of bone cement.(4)The biological properties of calcium phosphate bone cement modified with different ions are as follows:copper,strontium,magnesium,zinc,cobalt,lithium,selenium,and silicon have promoting angiogenesis/osteogenic effects.Iron,copper,magnesium,zinc,and silver have antibacterial properties.Magnesium ions have anti-inflammatory properties.Copper and selenium have anti-tumor properties.(5)In summary,magnesium ions can improve the setting time,injectability,and compressive strength of calcium phosphate bone cement,while also promoting neovascularization/osteogenesis,antibacterial properties,and have good application prospects for the treatment of bone defects with concurrent infections.In addition,copper also has anti-tumor properties,so copper ions have great potential in the treatment of bone defects caused by infections and tumors.However,relevant research is still in the basic research stage,and the effects of different ion doping concentrations and synthesis conditions on the physicochemical properties of calcium phosphate bone cement need to be further explored.At the same time,the impact of biological properties also needs to be studied and observed for a longer period of time.

Objective:To explore the patterns and causes of occupational exposure to infectious diseases (OEID) among frontline medical staffs (FMS) in coronavirus disease 2019 (COVID-19) isolation wards (CIW), and the particularity of post-OEID management and the measures to prevent OEID.Methods:A total of 1 061 FMS of Wuhan Huoshenshan Hospital from February 4 to March 21, 2020 were enrolled. The OEID of FMS was investigated and analyzed from the perspectives of FMS physical and psychological conditions, protective equipment, infection-control related regulations and procedures, local air quality, exposure patterns, and the particularity of emergency treatment after exposure.Results:The incidence of OEID among FMS was 2.0%(21/1 061). The nurses and doctors accounted for 95.2%(20/21) and 4.8%(1/21), respectively. The incidences in 17 general wards and two intensive care units (ICU) were 71.4%(15/21) and 28.6%(6/21), respectively. Nearly 90.5%(19/21) and 9.5%(2/21) of the OEID events occurred in contaminated area and potential contaminated area, respectively. About 23.8%(5/21) of the OEID events were air exposure of oral-nasal skin, mucosa and respiratory tract, which was secondary to uncontrollable vomiting, and 76.2%(16/21) were pricking injuries. The inducement factors involved poor quality and inappropriate wearing of some goggles, atomization of the inside of goggles leading to blurring vision, chest distress and decreased sense of touch and operational flexibility related to level-3 protection equipment, poor air quality, FMS physical and psychological conditions, etc. Under the direction of "the Procedures for Handling OEID" , all incidents are properly handled and no FMS was infected by 2019 novel coronavirus and blood-borne pathogens. No new OEID event was found after the strict implement of set of preventive measures.Conclusions:The OEID among FMS in CIW is attributed to multiple causes. The optimized process that takes into account the specificity of OEID management for both COVID-19 and blood-borne infectious diseases can effectively prevent potential post-exposure infections. And reasonable precautions can fully reduce the risk of OEID of FMS in CIW.

Epilepsy is a long-term, chronic, recurrent, multi-factorial, multi-symptomatic nervous system disease, and was caused by abnormal discharge of brain neurons. Etiology can cause irreversible brain dysfunction and even death. There are about 6.5 million children with epilepsy in China, with incidence rate twice that of adult, presenting serious threaten to children's growth and development. Vitamin D has been well-known for crucial importance to development of nervous, skeletal, and immune system. Studies have found that pediatric epilepsy as well as other neurological diseases were closely related with vitamin D deficiency. First, a large number of studies have shown that vitamin D in children with epilepsy is affected by epilepsy itself; second, the use of anti-seizure medicines can alter metabolism of vitamin D by inducing cytochrome oxidases; third, the inducement was concerned to varieties, combination and duration of anti-seizure medicines; fourth, it was expected that supplement of vitamin D during antiepileptic treatment would guarantee an improvement of treating given that anti-seizure medicines may lead to deficiency of vitamin D. Large numbers of researches have reported on the correlation ship between pediatric epilepsy and vitamin D. However, there is still a lack of systematic review. This article aims to retrospect the research progress of relationship between pediatric epilepsy and vitamin D, and provide valuable feedbacks on further treatment of pediatric epilepsy.

Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

To explore the effect of geniposidic acid (GPA) on the signal pathway of small heterodimer dimer receptor (SHP) and liver receptor homologue 1 (LRH-1) in cholestasis rats induced by alpha-naphthalene isothiocyanate (ANIT).
 Methods: Fifty SD rats were randomly divided into five groups: a blank group, an ANIT group, an ANIT+GPA (100 mg/kg) group, an ANIT+GPA (50 mg/kg) group, and an ANIT+GPA (25 mg/kg) group (n=10 in each group). The GPA were intragastrically given to rats for 10 days, and the control group and the ANIT group were given normal saline. At the eighth day of administration, all rats except the blank group were given 65 mg/kg ANIT once until the tenth day. After the last administration, serum total cholesterol (TC), triglyceride (TG) and total bile acids (TBA) were measured. The primary hepatocytes (RPH) were isolated from normal rats and cultured. The cells were divided into a blank group, an ANIT (40 μmol/L) group, an ANIT (40 μmol/L)+GPA (4.00 mmol/L) group (A4.00G group), an ANIT (40 μmol/L)+GPA (1.00 mmol/L) group (A1.00G group), and an ANIT (40 μmol/L)+GPA (0.25 mmol/L) group (A0.25G group). The mRNA transcription levels of SHP and cholesterol 7 alpha hydroxylase (CYP7A1) in RPH were detected by real-time-PCR, and the protein levels of SHP and CYP7a1 were detected by Western blotting. In the LRH-1 silence experiment, the RPH were divided into a blank group, a negative transfection group, a siRNA-LRH group (ZR group), a siRNA-LRH+GPA (4.00 mmol/L) group (ZR4.00G group), a siRNA-LRH+GPA (1.00 mmol/L) group (ZR1.00G group) and a siRNA-LRH+GPA (0.25 mmol/L) group (ZR0.25G group). The protein and mRNA levels of SHP, CYP7a1, LRH-1 were detected. In the over-expression experiment, the RPH were also divided into a blank group, a negative transfection group, a LRH-1 over-expression plasmid group (OE group), a LRH-1 over-expression plasmid+GPA (4.00 mmol/L) group (OE4.00G group), a LRH-1 over-expression plasmid+GPA (1.00 mmol/L) group (OE1.00G group), and a LRH-1 over-expression plasmid+GPA (0.25 mmol/L) group (OE0.25G group). The protein and mRNA levels of SHP, CYP7a1 and LRH-1 were detected.
 Results: Compared with the blank control group, TC and TBA were significantly increased (both P<0.01) in the ANIT group, but there was no difference in TG; compared with the ANIT group, the contents of TC and TBA in the AG100 and AG50 groups were significantly reduced (all P<0.01). Compared with the blank control group, the proteins and mRNA levels of SHP were significantly decreased (P<0.01), while CYP7a1 were dramatically increased (P<0.01) in the ANIT group; compared with the ANIT group, the proteins and mRNA levels of SHP in the A4.00G group and the A1.00G group were significantly increased (both P<0.01), while the levels of CYP7a1 proteins and mRNA levels were evidently decreased in the A4.00G and A1.00G groups (both P<0.01). Compared with the negative transfection group, the proteins and mRNA levels of CYP7a1 and LRH-1 were dramatically restrained (all P<0.01), while there was no change in SHP in the ZR group; compared with the ZR group, the proteins and mRNA levels of SHP were significantly increased (all P<0.01), while LRH-1 and CYP7a1 were not changed in the ZR4.00G, ZR1.00G and ZR0.25G groups. Compared with the negative transfection group, the protein and mRNA levels of CYP7a1 and LRH-1 were significantly suppressed in the OE group (all P<0.01). Compared with the OE group, the protein and mRNA levels of SHP were evidently increased in the OE4G and OE1G groups (all P<0.01), while LRH-1 and CYP7a1 were not changed in the OE4G, OE1G and OE0.25G groups.
 Conclusion: The over-expression of LRH-1 in RPH can up-regulate the mRNA and protein levels of CYP7a1. GPA can improve the biochemical and liver pathology of ANIT-induced cholestasis rats, which may be related to the decrease of CYP7a1 by activating SHP through LRH-1 in RPH.
Animals ; Cholestasis ; Iridoid Glucosides ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; Signal Transduction

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.