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.

Objective To investigate the clinical efficacy of oblique lumbar interbody fusion(OLIF)combined with poste-rior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots(RNRs).Meth-ods A retrospective analysis of 92 patients with lumbar spinal stenosis treated by oblique lateral lumbar interbody fusion com-bined with posterior percutaneous internal fixation from June 2019 to June 2022 was performed.There were 32 males and 60 females,aged from 44 to 82 years old with an average of(63.67±9.93)years old.All patients were divided into RNRs positive group and RNRs negative group according to redundancy or not before operation.There were 38 patients in RNRs positive group,including 15 males and 23 females.The age ranged from 45 to 82 years old with an average of(65.45±10.37)years old.The disease duration was 24.00(12.00,72.00)months.There were 54 patients in RNRs negative group,including 17 males and 37 females.The age ranged from 44 to 77 years old with an average of(62.42±9.51)years old.The disease duration was 13.50(9.00,36.00)months.The general data of patients were recorded,including operation time,intraoperative blood loss and complications.The imaging parameters before and after operation were observed,including the number of stenosis segments,intervertebral space height,lumbar lordosis angle and dural sac area.The visual analogue scale(VAS)was used to evaluate the back and lower extremity pain,and the Oswestry disability index(ODI)was used to evaluate the activities of daily living.Results All patients were followed up for 8 to 18 months with an average of(11.04±3.61)months,and no complications were found during the follow-up period.The number of stenosis segments in RNRs positive group(1.71±0.46)was more than that in RNRs negative group(1.17±0.38).In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,ODI score were(1.11±0.19)cm,(0.46±0.17)cm2,(5.39±1.00)scores,(5.05±1.01)points,(55.74±4.05)points,respectively.RNRs negative groups respectively(0.97±0.23)cm,(0.69±0.26)cm2,(4.50±0.77)scores,(4.00±0.58)scores,(47.33±3.43)％.In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,leg pain VAS,ODI score were(1.60±0.19)cm,(0.74±0.36)cm2,(3.39±0.72)scores,(3.05±1.01)scores,(46.74±4.82)scores,respectively.RNRs negative groups respectively(1.48±0.25)cm,(1.12±0.35)cm2,(3.00±0.82)scores,(3.00±0.82)scores,(37.67±3.58)％.The postoperative intervertebral space height,dural sac area,low back pain VAS score,lower extremity pain VAS and ODI score of the patients in the RNRs positive group and the negative group were signifi-cantly improved compared with those before operation,and the differences were statistically significant(P＜0.05).There were statistically significant differences in the number of stenosed segments,preoperative intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,and ODI between the two groups(P＜0.05).There were significant differences in postoperative intervertebral space height and postoperative ODI between the two groups(P＜0.05),but there was no significant difference in intervertebral space height before and after operation and ODI score before and after operation(P＞0.05).There were significant differences in operation time,intraoperative blood loss,postoperative dural sac area,difference of dural sac area before and after operation,postoperative low back pain VAS,difference of low back pain VAS score before and after oper-ation,difference of lower extremity pain VAS before and after operation between the two groups(P＜0.05).Conclusion OLIF combined with posterior percutaneous internal fixation has a good effect on patients with or without RNRs.Multi-segmental lumbar spinal stenosis and decreased dural sac area may lead to the occurrence of RNRs,and LSS patients with RNRs have more severe symptoms.LSS patients with RNRs have worse surgical outcomes than those without RNRs.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI ^ 1. With the increase of the proportion of serum, the inhibitory rate of 10% ~ 90% drug-containing serum to pseudomonas aeruginosa (standard/resistant) increased gradually.compared with the control group, the inhibitory effect of the Qiguiyin group on bacteria was significantly enhanced. The MIC

OBJECTIVE: To investigate the clinical significance and screen the risk factors of redundant nerve roots(RNRs) in patients with lumbar spinal stenosis. METHODS: The clinical data of 196 patients with lumbar spinal stenosis in the department of Spinal Surgery, Yijishan Hospital, Wannan Medical College from April 1, 2015 to November 30, 2020 were retrospectively analyzed. All patients were divided into RNRs positive group and RNRs negative group according to the presence of RNRs. The differences in general clinical data, imaging parameters, visual analogue scale(VAS), Oswestry disability index(ODI), and other indicators between the two groups were compared. The risk factors which are highly correlated with RNRs were screened by binary Logistic regression analysis. RESULTS: There were 59 cases in the RNRs positive group, with an occurrence rate of 29.95% (59/137), and 137 cases in the RNRs negative group. The incidence rate of RNRs in 196 patients with lumbar spinal stenosis was 30.10% (59/196). VAS and ODI scores of patients in the two groups were statistically significant (P<0.05), and clinical symptoms of patients in the RNRs positive group were more severe than those in the RNRs negative group. There were significant differences in age, number of stenosis segments, average area of lumbar dural sac, area of the narrowest segment and the narrowest segment(P<0.05). Binary logistic regression analysis showed that the number of stenosis segments, the average median sagittal diameter of spinal canal, and the average area of dural sac in lumbar intervertebral space were correlated with the generation of RNRs (P<0.05). The regression coefficient of the number of stenosis segments was -1.115, the regression coefficient of the median sagittal diameter of the spinal canal was -1.707, and the regression coefficient of the mean dural sac area of the lumbar intervertebral space was 7.556. CONCLUSION The clinical symptoms of patients with lumbar spinal stenosis accompanied by RNRs are more severe than those without them. The number of narrow segments, median sagittal diameter of the spinal canal, and the area of the lumbar intervertebral dural sac are the high-risk factors for RNRs, with the area of the lumbar intervertebral dural sac has the highest correlation.
Humans ; Spinal Stenosis/surgery* ; Constriction, Pathologic ; Clinical Relevance ; Retrospective Studies ; Risk Factors

OBJECTIVE: To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA). METHODS: A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. RESULTS: A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study. CONCLUSIONS CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).
Humans ; Medicine, Chinese Traditional ; Osteoarthritis, Knee/therapy* ; Outpatients ; Quality of Life ; Treatment Outcome

OBJECTIVE: To investigate the relationship between spine-pelvic sagittal parameters and clinical efficacy before and after oblique lumbar interbody fusion(OLIF). METHODS: A retrospective analysis of clinical data of 65 patients with lumbar degenerative diseases treated with OLIF were performed from July 2017 to July 2018. There were 26 males and 39 females aged from 33 to 79 years old with an average of (62.72±10.23) years old. Oswestry Disability Index (ODI) and visual analogue scale (VAS) before and at the latest follow up were evaluated. Disc height (DH) and spine- pelvic sagittal parameters of the surgical segment were measured before and at the latest follow- up, including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL). According to the difference of PI-LL, it was judged whether PI and LL match and the patients were grouped, PI-LL ranged from -9° to 9° was set as matching group, and PI-LL less than -9° or larger than 9° was set as mismatching group. The spine-pelvic sagittal parameters were analyzed before and at the latest follow-up of OLIF in patients with lumbar degenerative diseases, and the correlation between changes and clinical efficacy was compared. RESULTS: All patients were followed up from 8 to 20 months with an average of (14.20±3.68) months. Operation time was (91.54±25.97) min, intraoperative blood loss was (48.15±10.14) ml, and the hospitalization time ranged from 6 to 19 days with an average of (9.28± 2.50) days. Totally 84 surgical levels, 46 patients were single segment and 19 patients were double segments. VAS and ODI score were improved from (4.88±0.99) point, (67.60±13.73) % preoperatively to (2.85±1.30) points, (30.57±6.48) % at the latest follow-up. There were significant differences in VAS and ODI scores between before and at the latest follow-up. The sagittal parameters of LL, PT, SS, PI, PI -LL and the surgical level DH were (42.80 ±16.35)° , (23.22 ±10.91)° , (26.95 ± 13.30)°, (50.22±14.51)°, (7.53±16.13) °, (0.91±0.29) cm preoperatively and improved to the latest follow-up (49.95± 12.82) °, (17.94±9.24) °, (33.71±12.66) °, (51.65±10.26) °, (1.68±17.00) °, (1.20±0.40) cm;there were statistical differences in LL, PT, SS, PI-LL, DH before operation and at the latest follow up, while no difference in PI. LL of preoperative PI-LL in matched group was (48.76±11.09)° , and (38.00±18.37)° in PI-LL mismatch group, there was difference between two groups. There were no differences in VAS, ODI, PT, SS, PI and DH between two groups. At the latest follow-up, ODI between PI-LL matched group and PI-LL mismatched group were (29.40±5.93)% and (32.86±7.02)% respectively, and had difference in ODI between two groups;while there were no significant differences in VAS, LL, PT, SS, PI, and DH. Pearson correlation analysis showed preoperative PT-LL was positively correlated with VAS;PT was positively correlated with ODI at the latest follow-up. CONCLUSION OLIF has a good surgical effect on lumbar degenerative diseases, and could change spine-pelvic sagittal parameters of patient to a certain extent, and further restoring the balance of the sagittal plane of lumbar spine.
Adult ; Aged ; Female ; Humans ; Lumbar Vertebrae ; Lumbosacral Region ; Male ; Middle Aged ; Pelvis ; Retrospective Studies ; Spinal Fusion ; Treatment Outcome

OBJECTIVE: To systematic evaluate the outcome of open-wedge high tibial osteotomy(OWHTO) and unicomartmental knee arthroplasty (UKA) in treating medial compartment osteoarthritis of the knee. METHODS: According to the retrieval strategy made by the Cochrane collaboration, a computer-base research of Medline, Pubmed, EMbase, Cochrane Library, CBM, CNKI, and Wanfang databases was performed and search deadline was March 2018. Related Chinese and English orthopedic journals and conference papers were manually searched. Controlled studies of OWHTO and UKA in the treatment of medial knee osteoarthritis were included. The quality of included researches was evaluated, and the data of postoperative knee function, complications, total knee arthroplasty(TKA) revision rates, and postoperative pain were extracted. Meta analysis was performed using the RevMan 5.0 software. RESULTS: A total of 8 articles that met the criteria were included containing a total of 675 patients. Meta-analysis showed that there was no significant difference in postoperative HSS score, knee score, functional score, and Lysholm score between the OWHTO and UKA groups(=0.32, =0.87, =0.22, =0.53). The range of joint motion in the OWHTO group was better than that in the UKA group, and the difference was statistically significant(=0.009). There was no significant difference in postoperative complications and the rates of revision to TKA between the two groups(=0.81, =0.23). There was no difference in postoperative knee pain between the two groups. CONCLUSIONS In the treatment of medial compartmental osteoarthritis of the knee that meets the surgical indications, OWHTO had better postoperative joint mobility. The results were similar in postoperative knee score, postoperative complications, and postoperative TKA revision rates between OWHTO and UKA groups.
Arthroplasty, Replacement, Knee ; Humans ; Knee Joint ; Osteoarthritis, Knee ; Osteotomy ; Tibia ; Treatment Outcome

【Objective】To investigate the differences of lung involvement between dengue and severe dengue.【Methods】227 dengue patients admitted in The Third Affiliated Hospital of Sun Yat-sen University from July 2014 to October 2018 were enrolled. The clinical characteristics，treatment and outcome of the patients were analyzed to explore the differences of lung involvement between dengue and severe dengue （SD）. 【Results】 The rate of old age ，smoking ，hypertension，diabetes and cerebrovascular disease was higher in dengue with lung involvement group（DWLI）than dengue without lung involvement group（DWOLI）（χ2 were 25.146，3.847，10.326，7.177，and 5.355，P was 0.050 for smoking，the others were < 0.05）. The rate of cough and breathlessness was higher in DWLI（χ2 were 11.465 and 6.068，P were 0.001 and 0.014），as well as in SD subgroup（χ2 were 4.585 and 6.717，P were 0.032 and 0.010）. C-reactive protein and procalcitonin were increased in DWLI（Z were - 2.591 and - 3.033，P were 0.010 and 0.002）. The rate of pleural effusion was higher in SD subgroup（χ2 = 4.987，P = 0.026）. Bilateral lung infiltration was correlated with SD（χ2 = 5.910，P =0.015）. The rate of acute liver injury，acute kidney injury and multi-organ dysfunction syndrome（MODS）was higher in DWLI（χ2 were 7.044，7.059，and 11.315，P were 0.008，0.008 and 0.001）. The rate of anti-virus，anti-bacteria and combined therapy was higher in DWLI（χ2 were 13.156，32.845，and 12.684，P all were < 0.001）.【Conclusion】Dengue patients who were with old age，smoking，or suffered from underlying disease of hypertension，diabetes and cerebrovascular disease were vulnerable to lung involvement. Cough，breathlessness，pleural effusion and bilateral lung infiltration were signs of severe dengue. Attention should be paid to dengue with lung involvement.

Objective To explore the infection distribution and drug resistance of pathogens in patients with severe liver disease,and provide reference for clinical medication.Methods Retrospective analysis of the microbiological specimens from patients with severe liver disease in Department of Infection of our hospital from August 2014 to November 2016 and the drug susceptibility testing were carried out by means of K-B disc diffusion method after bacterial culturing,and the distribution and drug resistance of pathogens were analyzed.Results Totally 17 of 73 patients with severe liver disease developed hospital infection (23.3％).104 strains of bacteria were isolated and 78 strains out of them were multidrug-resistant bacteria (75.0％).Among them,28(26.9％) strains were gram-positive coccus,mainly consisting of Staphylococcus aureus and Staphylococcus epidermidis,and 58(55.8％) were gram-negative coccus,mainly composed of Escherichia coli,Klebsiella pneumonia and Acinetobacter baumannii,and 18(17.3％) strains fungi.S.aureus and enterococci were resistant to penicillin,erythromycin and levofloxacin,the resistance rates were above 80.0％,but had low resistance rates to vancomycin,teicoplanin and tigecycline.The resistance rates of E.coli and K.pneumoniae to piperacillin,cefazolin and cefuroxime sodium were above 85.0％,but they had lower resistance rates to tigecycline and amikacin.Acinetobacter baumannii was 100％ resistant to piperacillin and tazobactam,ceftazidime,imipenem and amikacin,but had low resistance to tigecycline and minocycline.Conclusions Multi-drug resistant bacteria are the main bacterial pathogens in patients with severe liver disease and have a high resistance rate to commonly used antibiotics,empirical treatment in the population at high risk of multidrug-resistant bacteria infections requires the use of broad-spectrum or high-grade antibiotics (e.g.carbapenems or tigecycline) and drugs against specific pathogenic bacteria (glycopeptides,linezolid,and amikacin etc).Early de-escalation policies are recommended to prevent the spread of multidrug-resistant bacteria in cirrhosis.