Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

Perioperative intravenous infusion of dexmedetomidine for alleviating postpartum depression after cesarean section: A meta-analysis and systematic review.

The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = -1.25, 95 %CI: -1.73 to -0.77; SMD = -1.08, 95 %CI: -1.43 to -0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta-regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 µg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods.

Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD. Objective: To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery. Design, Setting, and Participants: This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible. Interventions: Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 µg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively. Main Outcomes and Measures: The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis. Results: All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02). Conclusions and Relevance: Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.

Predicting efficacy of sub-anesthetic ketamine/esketamine i.v. dose during course of cesarean section for PPD prevention, utilizing traditional logistic regression and machine learning models.

OBJECTIVE: Increasing researches supported that intravenous ketamine/esketamine during the perioperative period of cesarean section could prevent postpartum depression(PPD). With the effective rate ranging from 87.2 % to 95.5 % in PPD, ketamine/esketamine's responsiveness was individualized. To optimize ketamine dose/form based on puerpera prenatal characteristics, reducing adverse events and improving the total efficacy rate, prediction models were developed to predict ketamine/esketamine's efficacy. METHOD: Based on two randomized controlled trials, 12 prenatal features of 507 women administered the ketamine/esketamine intervention were collected. Traditional logistics regression, SVM, random forest, KNN and XGBoost prediction models were established with prenatal features and dosage regimen as predictors. RESULTS: According to the logistic regression model (ain = 0.10, aout = 0.15, area under the receiver operating characteristic curve, AUC = 0.728), prenatal Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, thoughts of self-injury and bad mood during pregnancy were associated with poorer ketamine efficacy in PPD prevention, whilst a high dose of esketamine (0.25 mg/kg loading dose+2 mg/kg PCIA) was the most effective dosage regimen and esketamine was more recommended rather than ketamine in PPD. The AUCvalidation set of KNN and XGBoost model were 0.815 and 0.651, respectively. CONCLUSION: Logistic regression and machine learning algorithm, especially the KNN model, could predict the effectiveness of ketamine/esketamine iv. during the course of cesarean section for PPD prevention. An individualized preventative strategy could be developed after entering puerpera clinical features into the model, possessing great clinical practice value in reducing PPD incidence.

Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.

OBJECTIVE: To investigate the association of postpartum depressive symptoms (PDS) and self-harm ideation with n-methyl-d-aspartate (NMDA) receptor GRIN2B and GRIN3A gene polymorphisms and other risk factors in women undergoing cesarean section. METHODS: A total of 362 parturients undergoing cesarean section under lumbar anesthesia were selected and their postpartum depression level was assessed by the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum, with an EPDS score of 9/10 as the cut-off value. Three GRIN2B SNP loci (rs1805476, rs3026174, rs4522263) and five GRIN3A SNP loci (rs1983812, rs2050639, rs2050641, rs3739722, rs10989563) were selected for genotype detection. The role of each SNP, linkage disequilibrium and haplotypes in the development of postpartum depression was analyzed. Logistic regression analysis was performed for related risk factors. RESULTS: PDS incidence was 16.85%, and self-harm ideation incidence was 13.54%. Univariate analysis showed that GRIN2B rs1805476, rs3026174 and rs4522263 gene polymorphisms were associated with PDS (p < 0.05), with GRIN2B rs4522263 gene also associated with maternal self-harm ideation. GRIN3A rs1983812, rs2050639, rest rs2050641, rs3739722 and rs10989563 alleles were not associated with PDS. Logistic regression analysis indicated that high pregnancy stress, as well as rs1805476 and rs4522263 alleles were PDS risk factors following cesarean delivery. GRIN2B (TTG p = 0.002) and GRIN3A (TGTTC p = 0.002) haplotypes were associated with the lower PDS incidence and higher PDS incidence respectively. CONCLUSION: GRIN2B rs1805476 GG genotype, rs4522263 CC genotype and high stress during pregnancy were risk factors for PDS, whilst a significantly higher incidence of self-harm ideation was evident in parturients carrying GRIN2B rs4522263 CC genotype.

An optimization for postpartum depression risk assessment and preventive intervention strategy based machine learning approaches.

BACKGROUND: Postpartum depression (PPD) is one of the most common psychiatric disorders for women after delivery. The establishment of an effective PPD prediction model helps to distinguish high-risk groups, and verifying whether such high-risk groups can benefit from drug intervention is very important for clinical guidance. METHODS: We collected data of parturients that underwent a cesarean delivery. The Control group was divided into a training cohort and a testing cohort. Six different ML models were constructed and we compared their prediction performance in the testing cohort. For model interpretation, we introduced SHapley Additive exPlanations (SHAP). Then, training cohort, ketamine group and dexmedetomidine (DEX) group were classified as high or low risk for PPD by the model. A 1:1 propensity score matching (PSM) was performed to compare the incidence of PPD between two groups in different risk cohorts. RESULTS: Extreme gradient enhancement (XGB) had the best recognition effect, with an area under the receiver operating characteristic curve (AUROC) of 0.789 (95 % CI 0.742-0.836) in the training cohort and 0.744 (95 % CI 0.655-0.823) in the testing cohort, respectively. A threshold of 21.5 % PPD risk probability was determined. After PSM, the results showed that the incidence of PPD in the two intervention groups was significantly different from the control group in the high-risk cohort (P < 0.001) but not in the low-risk cohort (P > 0.001). CONCLUSION: Our study demonstrated that the XGB algorithm provided a more accurate in prediction of PPD risk, and it was beneficial to receive early intervention for the high-risk groups distinguished by the model.

Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting.

Additional effects of acupuncture on early comprehensive rehabilitation in patients with mild to moderate acute ischemic stroke: a multicenter randomized controlled trial.

BACKGROUND: Acupuncture is not considered a conventional therapy for post-stroke sequelae but it might have some additional positive effects on early rehabilitation. We conducted this trial to determine whether acupuncture has additional effects in early comprehensive rehabilitation for acute ischemic stroke and dysfunctions secondary to stroke. METHODS: Two hundred fifty patients were randomized into two groups: acupuncture (AG) or no acupuncture (NAG). Eighteen acupuncture treatment sessions were performed over a 3-week period. The primary outcome was blindly measured with National Institutes of Health Stroke Scale (NIHSS) at week 1, week 3, and week 7. Secondary outcomes included: Fugl-Meyer Assessment (FMA) for motor function, bedside swallowing assessment (BSA) and videofluoroscopic swallowing study (VFSS) for swallowing function, the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for cognitive function, and the adverse reaction of acupuncture for safety assessment. RESULTS: Significant improvements from acupuncture treatment were observed in NIHSS (p < 0.001), VFSS (p < 0.001), MMSE (p < 0.001), MoCA (p = 0.001), but not obtained from FMA (p = 0.228). Changes from baseline of all above variables (except FMA) also had the same favorable results. A significant improvement in FMA lower extremity subscale appeared in AG (p = 0.020), but no significant difference was found for the upper extremity subscale (p = 0.707). More patients with swallowing disorder recovered in AG (p = 0.037). Low incidence of mild reaction of acupuncture indicated its safety. CONCLUSIONS: This trial showed acupuncture is safe and has additional multi-effect in improving neurologic deficits, swallowing disorder, cognitive impairment, and lower extremity function, but has no significant improvement for upper extremity function during this short-term study period. TRIAL REGISTRATION: Chictr.org ChiCTR-TRC -12001971 (March 2012).

Comprehensive rehabilitation with integrative medicine for subacute stroke: A multicenter randomized controlled trial.

To determine whether integrative medicine rehabilitation (IMR) that combines conventional rehabilitation (CR) with acupuncture and Chinese herbal medicine has better effects for subacute stroke than CR alone, we conducted a multicenter randomized controlled trial that involved three hospitals in China. Three hundred sixty patients with subacute stroke were randomized into IMR and CR groups. The primary outcome was the Modified Barthel Index (MBI). The secondary outcomes were the National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer Assessment (FMA), the mini-mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA), Hamilton's Depression Scale (HAMD), and the Self-Rating Depression Scale (SDS). All variables were evaluated at week 0 (baseline), week 4 (half-way of intervention), week 8 (after treatment) and week 20 (follow-up). In comparison with the CR group, the IMR group had significantly better improvements (P < 0.01 or P < 0.05) in all the primary and secondary outcomes. There were also significantly better changes from baseline in theses outcomes in the IMR group than in the CR group (P < 0.01). A low incidence of adverse events with mild symptoms was observed in the IMR group. We conclude that conventional rehabilitation combined with integrative medicine is safe and more effective for subacute stroke rehabilitation.

Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial.

INTRODUCTION: Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. METHODS AND ANALYSIS: 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks' follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. ETHICS AND DISSEMINATION: Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561.

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

BACKGROUND: Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. METHODS/DESIGN: In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. DISCUSSION: This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

[Motor dysfunction in stroke of subacute stage treated with acupuncture: multi-central randomized controlled study].

OBJECTIVE: To verify the clinical efficacy of acupuncture on motor dysfunction in ischemic stroke of subacute stage. METHODS: The multi-central randomized controlled trial was adopted. One hundred and twenty-six cases of ischemic stroke of subacute stage were randomized into an acupuncture group (61 cases) and a conventional treatment group (65 cases). The basic treatment of western internal medicine and rehabilitation training were applied to the patients of the two groups. In the acupuncture group, acupuncture was supplemented at the body points located on the extensor of the upper limbs and the flexor of the lower limbs. In combination, scalp acupuncture was applied to NS5, MS6 and MS6 on the affected side. The treatment was given 5 times a week and totally 8 weeks were required. The follow-up observation lasted for 3 months. The scores in Fugl-Meyer scale and NIHSS scale and Barthel index were compared between the two groups before treatment, in 4 and 8 weeks of treatment and the 3-month follow-up observation after treatment separately. RESULTS: In 4 and 8 weeks of treatment and the follow-up observation, Fugl-Meyer scale score was improved obviously in the patients of the two groups (all P<0. 01). In 8 weeks of treatment and the follow-up observation, Fugl-Meyer scale score in the acupuncture groupwas im proved much apparently as compared with that in the conventional treatment group [68. 0 (43. 0,86. 5) vs 52. 5 (30.3, 77.0), 77.0 (49.5, 89.0) vs 63. 0 (33.0, 84.0), both P<0. 05]. Except that NIHSS scale score was not reduced apparently in 4 weeks of treatment in the conventional treatment group (P>0.05), the results of NIHSS scale at the other time points were all decreased obviously as compared with those before treatment in the patients of the two groups (all P<0. 01). In 8 weeks of treatment and the follow-up observation, the results in the acupuncture group were reduced much apparently as compared with those in the conventional treatment group [5. 0 (3.0,8.0) vs 7. 0 (3.0,13.8), 4. 0 (1.5,7.0) vs 6.0 (2.0,11.7) ,both P<0. 05]. In 8 weeks of treatment and the follow-up observation, Barthel index was improved obviously as compared with that before treatment in the patients of the two groups (all P<0. 05). The improvement in the acupuncture group was much more significant as compared with the conventional treatment group [75. 0 (60. 0,87. 5) vs 65. O (36. 3, 87. 5), P<0. 051. CONCLUSION: Based on the conventional treatment, Acupuncture achieves the satisfactory clinical efficacy on motor dysfunction in ischemic stroke of subacute stage.

[Effects and mechanism of low-intensity pulsed ultrasound on extracellular matrix in rabbit knee osteoarthritis].

OBJECTIVE: To observe the effects of low-intensity pulsed ultrasound (LIPUS) on repairing extracellular matrix in rabbit knee osteoarthritis and analyze its mechanism. METHODS: Sixty adult female rabbits with an average weight of (2.0 ± 0.2) kg, were divided randomly into two groups (experimental group and control group, 30 rabbits in each group). All rabbits were replicated in right knees by Hulth method for knee osteoarthritis model. Two weeks after operation, the rabbits in experimental group were treated with LIPUS, and the ultrasonic frequency was (800 ± 5%)KHz and the maximum intensities of spatially averaged and time averaged (SATA) was (50 ± 10%) mw/cm2, for 1 time a day and every time 20 min, while the rabbits in control group were treated with sham LIPUS,the same operation with experimental group but without energy output. At the 2, 4, 8 weeks after treatment, 10 rabbits in each group were randomly killed for each time. The general changes of cartilage and its histopathological changes by HE staining were observed; the expression of collagen type II, proteoglycan, MMP-3, 7, 13 in cartilage were analyzed by immunohistochemical and RT-PCR technique; and the expression of NO in cartilage was analyzed by nitrate reduction method. RESULTS: On the same observed time point, the damage degree of cartilage in experimental group was slighter than that of control group (P < 0.01), the expression of MMP-3, 7, 13 and NO in cartilage in experimental group was lower than that of control group (P < 0.01) while collagen type II and proteoglycan was higher than that of control group (P < 0.01). CONCLUSION: Low-intensity pulsed ultrasound can repair the damaged cartilage by reducing the expression of MMP-3, 7, 13, inhibiting the secretion of NO and promoting the synthesis of collagen type II and proteoglycan in cartilage.

[Research advance on signaling pathways and protein metabolism for skeletal muscle disuse atrophy].

Disuse atrophy of skeletal muscle is a common clinical problem and its exact mechanisms have not been fully understood. Previous studies suggested that disuse muscle atrophy is realized through the activation of one or more cell signaling pathways, but studies have shown that disuse atrophy is the activation of the ubiquitin-proteasome caused extensive decomposition of the protein. The present researches for disuse atrophy mainly focus on regulatory role in the upstream signaling molecules MuRF1 and Atroginl/MAFbx by NF-kappaB, IGF-1/PI3K/Akt, TGF-beta/Smad and MAPK signal pathway and a plurality of signal pathway activation or inhibition and interaction,and then through the ubiquitin--proteasome to influence the metabolism of protein. But regulation of expression of MuRF1 and Atroginl/MAFbxs still to be studied. Participate in disuse atrophy also needs to be further studied with atrophy confirmation and functional gene verification. The paper summarized recent original articles about the researches of skeletal muscle disuse atrophy and reviewed the various signal pathways and related u-biquitin-proteasome protein metabolism of disuse muscle atrophy.

[Basic research progress of knee osteoarthritis].

The exact etiology and pathogenesis of knee osteoarthritis (KOA) are still unknown and it is hard to treat the disease fundamentally. With new therapeutic methods and techniques appearing, the present situation of treating the disease will be changed in the near future. Basic research of knee osteoarthritis will contribute to clarifying the pathogenesis and exploring the therapeutic methods. This article makes a brief review on the up-to-date basic researches of knee osteoarthritis by reviewing literature concerned in recent years.

[Effect of HSP70 on apoptotic of cartilage cells in knee osteoarthritis].

OBJECTIVE: To investigate the expression and relationship between HSP70 and caspase-3 in knee osteoarthritis. METHODS: Forty adult SD rats were divided into experimental group and control group. Thirty rats in experimental group, anterior cruciate ligament transaction (ACLT) was cut off and partial meniscectomy of 1/3 inside incision were performed to reproduce knee osteoarthritis (KOA) model according to Hulth methos, and the other 10 rats was treated with nothing as control group. The rats were sent to the cage and free to move. At 1, 2 and 4 weeks later, the arthritis cartilage of femoral and tibial end were observed through immunohistochemistry staining and light microscope. Meanwhile, Mankin scale system was adopted for histomorphology evaluation. RESULTS: Changes of KOA such as hyperplastic synovium,erosion on the surface of cartilage and so on were found in experiment group, the expression of HSP70 was augmentation all the time, but the expression of caspase-3 was reduction 1 week later; no similar changes were found in control group. Mankin scale system showed that there were significant differences in the first week as compared with the second week and 4th week (both P < 0.01). CONCLUSION: Heat shock protein inhibit the apoptosis of cartilage cells and protect the cartilage cells in knee osteoarthritis, the conservative treatment for clinical provide objective scientific basis.

Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis.

An enhanced expression of the inflammatory mediators in the perimeniscal synovium in knee osteoarthritis (OA) has been suggested to contribute to progressive cartilage degeneration. However, whether the expression levels of these molecules correlated with the severity of OA still remained unclear. Medial perimeniscal synovial samples were obtained from 23 patients with Kellgren-Lawrence (K/L) grades 2 to 4 of medial knee OA. Immunohistochemical analysis of the synovium revealed that the MMP-1, COX-2 and IL-1ß expression of the patients with K/L 4 to be significantly reduced in comparison to those with either K/L 2 or 3, while the TGF-ß expression showed the opposite. The synovial expression of MMP-1 and IL-1ß showed a significant negative correlation with the severity of OA, while that of TGF-ß again showed the opposite. In conclusion, although synovial inflammation remained active, the MMP-1, COX-2 and IL-1ß expression in synovium decreased depending upon the severity of OA, while the TGF-ß expression increased.

Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery.

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0-100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman's rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n = 34, r = 0.25, p = 0.18 and r = 0.08, p = 0.75, respectively) and WOMAC (n = 14, r = 0.35, p = 0.22 and r = 0.45, p = 0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n = 34, r = 0.55, p = 0.001 and r = 0.71, p = 0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.