Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Gastrointestinal dyskinesia is a central factor contributing to the development of functional dyspepsia(FD),which is characterized by the rupture of the gastrointestinal nerve-Cajal interstitial cell-smooth muscle network.Gan Yu Pi Xu are similar to endoplasmic reticulum stress(ERs)-mitochondrial autophagy homeostasis imbalance.Mitochondrial autophagy disorders are the biological basis of Pi Xu,and Gan Yu is the macroscopic manifestation of ERs,and regulation of ERs-mitochondrial autophagy pathway is an important way to prevent and control FD.In this paper,we start from the theory of"liver-spleen correlation",combine the changes of endoplasmic reticulum and mitochondria in the process of gastrointestinal dyskinesia,reveal the correlation between the pathogenesis of Gan Yu Pi Xu and the autophagy of ERs and mitochondria,and elucidate the mechanism of gastrointestinal dyskinesia by the method of Shu Gan Jian Pi,so as to provide a new point of view for the treatment of gastrointestinal dyskinesia in FD.

Objective:To investigate the safety,efficacy,and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM). Methods:The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety,efficacy,and prognosis of this treatment approach were evaluated. Results:Of the 17 patients,10 were male and 7 were female,with a median age of 56 (45-64) years. The stem cell engraftment rate was 100％,with a median neutrophil engraftment time of+10 (9-12) days and a median platelet engraftment time of+12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100％,with 2 cases of pulmonary infection,1 case of urinary tract infection,1 case of skin infection,and 11 cases of transient elevation of serum amylase. After transplantation,13 patients achieved a complete response (CR) or better,and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17;P=0.078). The median follow-up time was 18 (6-36) months,and 15 patients survived without progression,1 patient experienced disease progression,and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0％ and 83.9％,respectively. Conclusion:High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response,further improve therapeutic efficacy,and the transplant-related complications are controllable,making it a viable option worth promoting in clinical practice.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P＜0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P＜0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P＜0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P＜0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.

Objective To investigate the feasibility and clinical effect of the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy.Methods Between June 2018 and September 2022,the medical records of 15 patients with Neer Ⅱ b distal clavicular fracture treated with locking plate under arthroscope were retrospectively analyzed,including 9 males and 6 females,aged from 25 to 57 years old with an average of(42.50±7.75)years old,5 left shoulder,10 right shoul-der,and duration of the disease ranged from 4 to 7 days with an average of(5.16±0.98)d.Visual analog score(VAS),Con-stant-Murley shoulder joint score scale and Neer standard score were used before operation,1 month after operation and the last follow-up.Results All patients successfully completed the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy,with the operation time ranging from 0.3 to 1.0 h with an average of(0.55±0.24)h.All patients were healed at stage Ⅰ.The follow-up time ranged from 6 to 15 months with an average of(9.2±2.8)months.The preoperative VAS score was 7.23±0.67,the Constant-Murley shoulder joint score was(19.57±0.91),and the Neer standard score was(11.27±1.12);The VAS score was(1.56±0.81),the Constant-Murley shoulder joint score was(52.62±1.54),and the Neer standard score was(61.98±2.99)in the first month after operation;At the last follow-up,the VAS was(0.42±0.54),the Constant-Murley shoulder joint score was(91.24±1.97),and the Neer standard score was(93.24±3.38).The difference between VAS,Con-stant-Murley shoulder joint score and Neer standard score was statistically significant at one month postoperative and preoper-ative(P＜0.05),and the difference between the last follow-up visit and one month postoperative was statistically significant(P＜0.05).Conclusion The treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscope can restore the function of shoulder joint,with definite curative effect and feasibility.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.