Objective To evaluate the influence of routine lateral release to the clinical outcomes after total knee arthroplasty without patellar resurfacing.Methods The study involved all patients divided into two groups using a randomised group method.During total knee arthroplasty(TKA),forty-three patients were treated with lateral release in the treatment group,while Forty-two patients in the control group were not treated with lateral release.Both groups were assessed for anterior knee pain,patient satisfaction,Knee Surgery Society(KSS)score,KSS function score,patella score,and incidence of postoperative complications.Results After 24 months of follow-up,the treatment group was found to have a lower incidence of anterior knee pain compared to the control group(P<0.05),and there were no statistically significant differences in postoperative satisfaction,complication rate,KSS knee score,KSS function score,and patella score between the two groups(P>0.05).Conclusion The study suggests that routine lateral release can reduce anterior knee pain and does not increase the risk of postoperative complications after total knee arthroplasty without patellar resurfacing.

BACKGROUND:The incidence of osteoporosis significantly increases in the patients with rheumatoid arthritis,and it remains unclear whether the presence of a large number of immune complexes in serum promotes the onset and development of osteoporosis. OBJECTIVE:To investigate the correlation between serum immune complexes and osteoporosis in patients with rheumatoid arthritis. METHODS:(1)Clinical trial:Serum and clinical data of 50 healthy controls and 50 patients with untreated rheumatoid arthritis were collected and retrospectively analyzed.Total immune complex level in serum was compared between two groups.Correlation of serum total immune complexes with bone mineral density,bone turnover markers and other clinical indicators in patients with rheumatoid arthritis was analyzed.(2)Cell experiment:Peripheral blood mononuclear cells from healthy volunteers were isolated and cultured,and divided into four groups:rheumatoid arthritis group was added with total immune complex suspension from rheumatoid arthritis patients;normal control group was added with total immune complex suspension from healthy medical checkups;positive control group was added with α-MEM medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand,and negative control group was added with α-MEM medium.Tartrate-resistant acid phosphatase staining was performed to observe the formation of osteoclasts after 7 days of treatment, RESULTS AND CONCLUSION:(1)Clinical trial:The total immune complex and serum alkaline phosphatase levels in patients with rheumatoid arthritis were significantly higher than those in health controls(P＜0.01,P＜0.05).Pearson correlation analysis showed that serum total immune complex level was positively correlated with erythrocyte sedimentation rate(r=0.330,P=0.019),serum alkaline phosphatase(r=0.545,P=0.001),anti-cyclic citrullinate peptide(r=0.377,P=0.007)and c-terminal telopeptide of type Ⅰ collagen(r=0.738,P=0.001),and negatively correlated with lumbar bone mineral density(r=-0.595,P=0.001)in patients with rheumatoid arthritis.Binary Logistic regression analysis showed that age[odds ratio(OR)=1.086,95%confidence interval(CI)(1.022,1.154),P=0.008],anti-cyclic citrullinate peptide[OR=1.002,95%CI(0.999,1.005),P=0.035],c-terminal telopeptide of type Ⅰ collagen[OR=0.141,95%CI(0.015,8.900),P=0.008]and serum total immune complexes[OR=2.895,95%CI(1.228,6.827),P=0.001]were the influencing factors for abnormal bone mass(reduced bone mass or osteoporosis)in patients with rheumatoid arthritis.(2)Cell experiment:Tartrate-resistant acid phosphatase positive osteoclasts were observed in the positive control group,normal control group and rheumatoid arthritis group,and there were more osteoclasts in the rheumatoid arthritis group than in the normal control group(P＜0.01).To conclude,serum total immune complexes can be used as a potential serologic predictor of rheumatoid arthritis complicated with osteoporosis,and removing immune complexes in serum or interfering with the binding of immune complexes to their receptors may be an effective means for the prevention and treatment of rheumatoid arthritis complicated with osteoporosis.

Objective:To explore the efficacy and safety of eltrombopag in the treatment of immune thrombocytopenia secondary to connective tissue diseases.Methods:Totally 23 patients with immune associated thrombocytopenia secondary to connective tissue diseases who were treated with eltrombopag in the Department of Rheumatology, the First Affiliated Hospital of Soochow University, from January 2020 to December 2022 were selected as the treatment group. Additionally, 34 patients who did not receive eltrombopag during the same period were collected as the control group. Statistical analysis was conducted using SPSS 26.0 software. The t test or Wilcoxon rank-sum test were used to compare differences between groups of categorical data.The chi-square test or Fisher′s exact test was used to compare the differences between groups of quantitative data. Results:The highest overall response rate of the 23 patients was 82.6% (19/23), which occurred at the 12th week after treatment. The blood platelet count was significantly increased from baseline at the first week[(47±29)×10 9/L, t=-5.25, P<0.001], also at the 2nd week[(111±87)×10 9/L, t=-5.31, P<0.001], the 4th week[(150±104)×10 9/L, t=-6.23, P<0.001], the 12th week [(153±92)×10 9/L, t=-6.64, P<0.001], the 24th week[(134±83)×10 9/L, t=-7.11, P<0.001], and the difference was statistically significant. Compared with the conventional treatment group, patients in the eltrombopag group had a higher proportion of patients previously being treated with IVIG[60.9%(14/23) vs. 20.6%(7/34), χ2=9.57, P=0.002], a lower proportion of patients currently using IVIG[21.7% (5/23) vs. 61.8%(21/34), χ2=8.86, P=0.003], and a lower maximum daily dose of glucocorticoid use[80(50, 120)mg/d vs. 80(55, 115)mg/d, Z=-2.02, P=0.042], the differences were statistically significant. After being followed up for 24 weeks, no patients experienced any serious adverse reactions related to eltrombopag. Conclusion:Eltrombopag is effective and safe in the treatment of immune thrombocytopenia secondary to connective tissue diseases. It can be used as one of the choices for patients who failed to respond to conventional treatment or patients who could not tolerate high-dose glucocorticoids.

Background: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. Methods Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000040610SynopsisIt's a prospective, randomized controlled trial to explore the effect of peritoneal vaginoplasty with or without ovarian transposition following laparoscopic radical hysterectomy on sexual dysfunction in patients with cervical cancer. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.

Background: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. Methods Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000040610SynopsisIt's a prospective, randomized controlled trial to explore the effect of peritoneal vaginoplasty with or without ovarian transposition following laparoscopic radical hysterectomy on sexual dysfunction in patients with cervical cancer. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.

Background: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. Methods Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000040610SynopsisIt's a prospective, randomized controlled trial to explore the effect of peritoneal vaginoplasty with or without ovarian transposition following laparoscopic radical hysterectomy on sexual dysfunction in patients with cervical cancer. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Objective:To evaluate the safety and effectiveness of distal femoral osteotomy combined with arthroscopy in the treatment of valgus knee.Methods:A retrospective analysis was conducted on 24 patients (25 knees) with valgus knee osteoarthritis admitted to the First Hospital of Jiaxing from January 2017 to December 2020 who underwent distal femoral osteotomy combined with arthroscopic surgery and were fixed with domestically produced distal femoral locking plates. The changes in hip knee ankle angle (HKA), distal lateral femoral angle (LDFA), knee joint range of motion (ROM), and knee joint function score (HSS) of the American Special Surgery Hospital before and after surgery were statistically analyzed.Resultsl:A total of 24 patients (25 knees) were followed up for (15.6±2.3)months. HKA increased from (171.22±2.51)° before surgery to (179.24±1.86)° at the last follow-up; LDFA increased from (82.17±2.03)° before surgery to (88.57±1.53)° at the last follow-up; The differences were statistically significant ( P<0.05). The HSS score improved from preoperative (60.27±6.04) to the last follow-up (87.80±5.50), with a statistically significant difference (all P<0.05). One out of 25 knees experienced loss of osteotomy angle, without insufficient or excessive correction, infection, and non union of fractures. Conclusions:The use of distal femoral osteotomy combined with arthroscopic surgery for the treatment of valgus knee osteoarthritis is a safe and reliable method. Retaining the lateral bone hinge during osteotomy is an important factor in maintaining the osteotomy angle and fracture healing.

Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.