Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To investigate the impact of body mass index (BMI) on delayed extubation of patients with acute Stanford type A aortic dissection (ATAAD).Methods:A total of 400 ATAAD patients who were admitted to our hospital from October 2021 to October 2023 and underwent surgical treatment were selected as the research objects. According to BMI, they were divided into obese group (BMI≥28 kg/m 2, 119 cases) and non-obese group (BMI<28 kg/m 2, 281 cases). The differences of preoperative clinical characteristics, intraoperative and postoperative data between the two groups were compared. Starting from transferring to the ICU and ending with the first successful extubation, The risk factors of postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients were analyzed, and the predictive efficacy of related factors for postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients was evaluated. Results:Compared with the non-obese group, the proportion of hypertension, diabetes, admission heart rate, admission systolic blood pressure, admission diastolic blood pressure and preoperative white blood cell count in the obese group were significantly increased, and the differences were statistically significant ( P<0.05). The cardiopulmonary bypass time, aortic cross-clamp time, operation time, red blood cell transfusion volume, invasive mechanical ventilation time, secondary operation rate and total hospitalization cost in the obese group were significantly higher than those in the non-obese group, and the differences were statistically significant ( P<0.05). Univariate logistic regression analysis showed that BMI, cardiopulmonary bypass time, ascending aortic cross-clamp time, operation time, age, hypertension, and red blood cell transfusion were related factors for postoperative invasive mechanical ventilation time ≥48 h in ATAAD patients ( P<0.05). Logistic multivariate regression analysis showed that increased BMI ( OR=1.213, P<0.05) and increased age ( OR=1.020, P<0.05) were independent risk predictors of postoperative invasive mechanical ventilation time≥48 h in ATAAD patients. Receiver operating characteristic curve ( ROC) analysis showed that the area under the ROC curve ( AUC) of BMI for predicting the duration of postoperative invasive mechanical ventilation in ATAAD patients≥48 h was 0.682 ( P<0.05), and the best predictive cut-off value was 25.64 kg/m 2. Conclusion:BMI≥28kg/m 2 increases the difficulty of surgery and the duration of invasive mechanical ventilation in ATAAD patients. BMI has a high predictive value for the duration of invasive mechanical ventilation in ATAAD patients after surgery ≥48 h, and effective intervention measures can be formulated to improve the treatment effect of patients.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Bacillus subtilis is recognized as a generally-regarded-as-safe strain, and has been widely used in the biosynthesis of high value-added products, including N-acetylneuraminic acid (NeuAc) which is widely used as a nutraceutical and a pharmaceutical intermediate. Biosensors responding to target products are widely used in dynamic regulation and high-throughput screening in metabolic engineering to improve the efficiency of biosynthesis. However, B. subtilis lacks biosensors that can efficiently respond to NeuAc. This study first tested and optimized the transport capacity of NeuAc transporters, and obtained a series of strains with different transport capacities for testing NeuAc-responsive biosensors. Subsequently, the binding site sequence of Bbr_NanR responding to NeuAc was inserted into different sites of the constitutive promoter of B. subtilis, and active hybrid promoters were obtained. Next, by introducing and optimizing the expression of Bbr_NanR in B. subtilis with NeuAc transport capacity, we obtained an NeuAc-responsive biosensor with wide dynamic range and higher activation fold. Among them, P535-N2 can sensitively respond to changes in intracellular NeuAc concentration, with the largest dynamic range (180-20 245) AU/OD. P566-N2 shows a 122-fold of activation, which is 2 times of the reported NeuAc-responsive biosensor in B. subtilis. The NeuAc-responsive biosensor developed in this study can be used to screen enzyme mutants and B. subtilis strains with high NeuAc production efficiency, providing an efficient and sensitive analysis and regulation tool for biosynthesis of NeuAc in B. subtilis.
N-Acetylneuraminic Acid/metabolism* ; Bacillus subtilis/metabolism* ; Promoter Regions, Genetic/genetics* ; Binding Sites ; Biosensing Techniques

Boiling is a common processing method of Chinese medicine. Based on the book of Summary of Processing Methods Data of Traditional Chinese Medicine in Past Dynasties， the authors consulted herbal books in all ages， combined with modern processing laws and regulations in various provinces and cities， the boiling methods and Chinese medicine varieties in ancient and modern times， judgment method of the endpoint of processing， as well as the study on boiling methods of representative Chinese medicines were compiled and analyzed. After sorting， it was found that the application of boiling methods began in the Han dynasty， enriched and developed in the Northern and Southern dynasties， Tang， Song and Yuan dynasties， and reached its heyday in the Ming and Qing dynasties. However， the number of modern boiling varieties decreased and mainly focused on toxic Chinese medicines or those that need to change or moderate their medicinal properties， indicating the development of boiling methods entered a stable period. The varieties of excipients used in the modern age mainly considered factors such as convenience of use and easy access， and the boiling degree， time and times were commonly used to judge the endpoint of boiling process. The main purposes of using boiling method for Chinese medicines were to remove impurities， remove non-medicinal parts， change or moderate the medicinal properties， and eliminate or reduce adverse reactions， which can provide a reference for carrying out the common research of boiling method for Chinese medicines.

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTA^DA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTA^DA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTA^DA-PrL pathway facilitates emergence from sevoflurane anesthesia.
Anesthesia ; Animals ; Dopaminergic Neurons/metabolism* ; Rats ; Receptors, Dopamine D1/metabolism* ; Sevoflurane/pharmacology* ; Ventral Tegmental Area/metabolism*

Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to ＜256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to ＜342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P ＜ 0.05).No significant difference existed between the mild group and the control group(P ＞ 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P ＞ 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P ＜ 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ～ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value ＞ 628 or G/P value ＞ 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.

Objective: To study the efficacy and safety of Cefpodoxime proxetil granules in the treatment of acute bronchitis in children. Methods: One hundred and sixty children of the First People′s Hospital of Nanning from June to December 2018 with acute bronchitis were randomly divided into cefpodoxime group and cefaclor group, with 80 cases in each group.All patients received routine treatment.On this basis, 80 patients in the cefpodoxime group received oral Cefpodoxime proxetil granules 5 mg/kg (not more than 100 mg/time), twice a day; 80 patients in the cefaclor group received oral Cefaclor.The granules were 10 mg/kg (not more than 250 mg/time), 3 times a day, and the course of treatment was 5 days.The clinical efficacy and adverse reactions were observed. Results: The cure rate and effective rate of Cefpodoxime group were 91.3% (73/80 cases) and 95.0% (76/80 cases), respectively, while the cure rate and effective rate of Cefaclor group were 66.3%(53/80 cases) and 81.3%(65/80 cases), respectively, and the differences between the 2 groups were statistically significant (χ²=14.94, 7.23, all P<0.05). Sixty-three strains of pathogenic bacteria and 66 strains of pathogenic bacteria were obtained in Cefpodoxine group and Cefaclor group, respectively, and the detection rates of bacteria in the 2 groups were 78.75% and 82.50%, respectively.There was no significant diffe-rence in the number of bacterial strains and strains detected in each group (χ²=0.36, P>0.05), but the total bacterial clearance rate in Cefpodoxine group was 88.9%(56/63 cases) while the bacterial Clearance rate in Cefaclor group was 74.2%(49/66 cases), and the difference between the 2 groups was statistically significant (χ²=4.57, P<0.05). In particular, the bacterial clearance rate in Cefpodoxine group to Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae were significantly higher than those in Cefaclor group, while the bacterial Clearance rate of Proteus and Escherichia coli were lower than those in Cefaclor group.The incidence of adverse reactions in Cefpodoxine group and Cefaclor group were 5.0% and 3.8%, respectively, with no significant difference (P>0.05). Conclusions The clinical effect of Cefpodoxime pro-xetil granules in treating children with acute bronchitis is more significant than that of Cefaclor.It has high safety and no serious side effect.

Objective To introduce the application of 3D printing individualized plastic guide plate in the treatment of pelvic and acetabular fracture and to evaluate its application value.Methods From June 2016 to April 2017,the clinical data of eleven adult patients with pelvic and acetabular fracture was analyzed retrospectively.The pelvic CT scan was performed before operation to obtain the original data.Three-dimensional reconstruction performed by mimics 17.0 software with the data and the fracture reduction performed on the software.3D printing individualized plastic guide plate was designed and made to guide the pre-implantation plate bending and shaping.The pre implantation plate bending was completed according to the plastic guide.Postoperative Matta imaging score was used to evaluate fracture reduction,while the function of the hip joint was assessed by the Harris scores.Results All the operations were successfully completed.There were no adverse complications during or after the operation.Anatomical reduction was performed in 10 cases and functional reduction in 1 case.The excellent and good rate of Matta scores was 90.9%,excellent in 7 cases,good in 3 cases,fair in 1 case and no poor case.The excellent rate of Harris scores was 81.8%,excellent in 6 cases, good in 3 cases,fair in 2 cases and no poor case.Conclusion In the treatment of pelvic and acetabular fracture,the application of 3D printing individualized plastic guide plate may not only make mode simple and feasible and save time and materials,but also simplify the operation,reduce the difficulty of operation and hold satisfactory clinical effect.

Objective:To determine the content of all-trans-retinyl palmitate in multivitamin preparations. Methods: HPLC was used and the chromatographic column was Apollo Silica (250 mm × 4. 6 mm, 5 μm). The mobile phase consisted of hexane-isopro-panol (999. 5:0. 5) and the column temperature was 30 ℃. The detection wavelength was 325 nm and the flow rate was 1. 0 ml· min-1 . The injection volume was 100 μl. Results:The calibration curve of all-trans-retinyl palmitate was linear within the concentra-tion range of 0. 2260-0. 6780 IU·ml-1(0. 1243-0. 3729 μg·ml-1, r=0. 9999). The average recovery was 99. 86%, and RSD was 0. 64%(n=9). Conclusion:The method is simple,accurate,sensitive,reproducible and universal, which can be used for the con-tent determination of all-trans-retinyl palmitate in multivitamin preparations.