1.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
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.
2.Optimization of Anti-infective Program after Surgery for a Case of Infant Patient with Intussusception and Enterobrosis by Clinical Pharmacists
Changhai SU ; Junbao LIU ; Peitao XIE ; Duo HAO ; Xiaojuan ZHANG
China Pharmacy 2020;31(21):2672-2676
OBJECTIVE:To provide th e ideas a nd for individualized anti-infective treatment of infection after surgery for infants and young children with intussusception and enterobrosis ,and to provide reference for clinical pharmacists participating in the clinical treatment. METHODS :Clinical pharmacists optimized the anti-infection program for an 11-month-old infant patient infected after surgery with intussusception and enterobrosis in Ordos Central Hospital ;they put forward medication suggestions in respects of the selection of initial anti-infection treatment program ,drug replacement ,the selection of anti-infection treatment program after blood culture showed Enterococcus coli and Enterococcus faecium ,and dosage adjustment. RESULTS :According to the judgment of the common pathogens and the hospital or community infections in the infant patient with intussusception and enterobrosis,cefoperazone sulbactam 1.0 g,q12 h was adjusted to cefoperazone sulbactam 0.5 g,q8 h combined with Metronidazole chloride sodium injection 20 mL,q8 h;when the blood culture showed E. coli (ESBL-)and E. faecium ,it was recommended to add vancomycin 0.15 g,q12 h. After poor treatment ,it was recommended to adjust the vancomycin dose to 0.2 g,q8 h. All the above suggestions were adopted by doctors. And the child ’s body temperature dropped after treatment ,the blood culture turned negative and laboratory indicators returned to normal. The child was discharged smoothly. CONCLUSIONS :Infants and young children are special groups. Therefore ,before using antibiotics ,clinical pharmacists should evaluate the age ,body weight ,liver and kidney functions of infants and young children. They should also help doctors select and adjust drugs ,frequency and dosage on the basis of pharmacokinetic characteristics and safety ,so as to avoid adverse drug reactions while ensure curative effect.
3.Pharmaceutical Practice of Clinical Pharmacist Participating in a Penicillin Allergic Patient with Necrotizing Fasciitis Combined with Diabetes Mellitus
Na ZHAO ; Yongzhi SHI ; Peitao XIE ; Hailong SONG ; Na ZHANG ; Bin XIAO
China Pharmacy 2019;30(15):2143-2149
OBJECTIVE: To investigate the formulation of therapy plan and pharmaceutical care for a penicillin allergic patient with necrotizing fasciitis combined with diabetes mellitus. METHODS: A penicillin allergic patient with necrotizing fasciitis combined with diabetes mellitus was admitted to Ordos central hospital on March 30, 2018. According to the disease characteristics of the patient, clinical pharmacists conducted pharmaceutical care during the treatment process from the aspects of antiinfective drugs selection, monitoring points of necrotizing fasciitis, blood glucose monitoring, effects of hypoproteinemia on antibiotic pharmacokinetics-pharmacodynamics, and assisted the physician to develop a more reasonable and effective individualized therapentic regimen. RESULTS: For diabetes mellitus, the patient adjusted Insulin lispro injection (insulin pump), Acarbose tablets, Metformin hydrochloride tablets and Glimepiride tablets successively. For rapid atrial fibrillation with intraventricular differential conduction and ST-T changes, Metoprolol tartrate tablets were used to reduce heart rate. For necrotizing fasciitis, when choosing drugs to ensure the anti-infective effect, considering that the patient had penicillin allergic and hypoproteinemia, clinical pharmacists chose drugs with low protein binding rates and different from the mother nucleus and side chain of penicillin. Imipenem cilastatin for injection, Aztreonam for injection, Levofloxacin lactate and sodium chloride injection were used successively. Voriconazole for injection was adopted for anti-fungal treatment. Physicians adopted the suggestions of clinical pharmacists. Debridement through early thorough drainage and rational drug use, the patient’s condition was effectively controlled. CONCLUSIONS: Clinical pharmacists assist physicians to formulate and optimize whole course therapentic regimen so as to improve the safety and effectiveness of drug treatment.
4.Participation of Clinical Pharmacists in One Case of Late-onset Infection after Artificial Hip Joints Replace-ment
China Pharmacist 2018;21(2):302-305
In order to explore the value of clinical pharmacist in the anti-infective treatment of the patients with late-onset infec-tion after artificial hip joints replacement,clinical pharmacists performed ward round and pharmaceutical care for one patient with infec-tion around the artificial joints after artificial hip joints replacement three years ago. According to the relevant literatures,clinical phar-macist provided medical advice for physician from the following aspects: surgical interventions, drug choice and dosage adjustment, and participated in the medicine therapeutic scheme for the patient. Physicians partly accepted the suggestions of clinical pharmacists, and the symptoms and imaging examination results of the patient improved after the treatment,which provided guarantee for the follow-up treatment. It is of great significance for clinical pharmacists to participate in the formulation of clinical medication plan to improve the rational drug use in clinical anti-infection treatment.

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