BACKGROUND:The treatment of early knee osteoarthritis can be achieved through two knee preservation treatments:Unicondylar knee arthroplasty and high tibial osteotomy.However,further exploration is needed to determine whether there are differences in knee joint recovery between the two knee preservation surgeries at different stages after surgery. OBJECTIVE:To compare the efficacy and related complications of unicondylar knee arthroplasty and high tibial osteotomy in the treatment of varus osteoarthropathy of the knee,and to provide a reference for clinical decision. METHODS:A total of 103 patients with varus osteoarthritis of the knee underwent surgical treatment in the Affiliated Hospital of Nantong University from September 2018 to September 2022 were selected.Among them,86 patients were followed up for more than 1 year.According to different surgical methods,the patients were divided into unicondylar knee arthroplasty group(49 cases)and high tibial osteotomy group(37 cases).Knee function,pain,and line of force correction were evaluated before surgery,4 weeks,3 months,6 months,and 1 year after surgery in both groups.Hospital for special surgery knee score,functional score of Western Ontario and McMaster Universities Osteoarthritis Index,changes of lateral space of the knee joint,range of motion,proprioception(position sense),and postoperative activity recovery speed were evaluated comprehensively. RESULTS AND CONCLUSION:(1)There were no significant differences in preoperative hospital for special surgery knee score,Western Ontario and McMaster Universities Osteoarthritis Index score and lateral knee compartment size between the two groups.(2)The hospital for special surgery knee score of patients undergoing unicondylar knee arthroplasty was better than that of patients undergoing high tibial osteotomy within 4 weeks after surgery(P<0.05).At 3 and 6 months after surgery,compared with the improvement of the two groups,the hospital for special surgery knee score in the unicondylar knee arthroplasty group was lower than that in the high tibial osteotomy group,and the difference was significant(P<0.05).The range of motion flexion value and position perception of patients undergoing high tibial osteotomy were significantly better than those undergoing unicondylar knee arthroplasty 6 months after surgery(P<0.05).(3)The unicondylar knee arthroplasty group was better than the high tibial osteotomy group in terms of the speed of knee movement recovery(P<0.05).(4)However,there was no significant difference between the two groups in the change of hospital for special surgery knee score,range of motion,and the width of lateral knee space during 1-year follow-up.(5)All patients were followed up for more than 1 year,and no adverse complications were found during the follow-up.(6)It is indicated that the short-term effect of knee functional recovery in patients with high tibial osteotomy is better than that in patients with unicondylar knee arthroplasty,but there is no significant difference in medium-and long-term efficacy between the two kinds of surgery for medial knee arthritis.

Objective:To investigate the efficacy and safety of percutaneous trans-hepatic choledochoscopic lithotripsy (PTCSL) in the treatment of recurrent hepatobiliary calculi under enhanced recovery after surgery (ERAS) mode.Methods:Clinical data of 88 patients with recurrent hepatobiliary calculi, who were treated with PTCSL at Zhengzhou Central Hospital Affiliated to Zhengzhou University and the First Affiliated Hospital of Xi'an Jiaotong University between June 2022 and June 2024 were retrospectively analyzed, including 34 males and 54 females, aged (52.0±13.8) years. The scheme includes preoperative education, prophylactic antibiotic application, ensuring the quality of surgery, early postoperative feeding and activity, etc. The operation can be divided into two fashions: percutaneous transhepatic cholangial drainage and PTCSL, which can be completed in one stage (one-stage expansion method) or in two stages (staged expansion method). Clinical data such as gender, age, operative time, intraoperative blood loss, residual stone, and surgical complications were recorded.Results:All 88 patients underwent PTCSL under ERAS mode successfully, including 52 cases using one-stage expansion method and 36 cases using staged expansion method. The operative time was (53±20) min, the intraoperative blood loss was (9.7±3.8) ml, the postoperative hospital stay was (3.6±1.7) d, and the hospitalization cost was (17 500±4 700) yuan. Sixty-nine patients (78.4%, 69/88) had one-time stone removal in the first PTCSL. A total of 19 cases of residual stones were managed again by percutaneous sinus soft choledochoscopy, of which 12 cases were managed by one-time choledochoscopy, five cases by two-time choledochoscopy, and two cases by three-time choledochoscopy. The rate of residual stone was significantly higher in one-stage expansion method compared to staged expansion method [28.8% (15/52) vs. 11.1% (4/36), P=0.040]. No death, conversion to open surgery, or severe complications such as intra-abdominal hemorrhage or bile leakage occurred in the patients. No residual stones or recurrence were found during the follow-ups of (7.5±2.1) months after discharge. Conclusion:PTCSL under ERAS mode is safe and effective in the treatment of recurrent hepatobiliary calculi.

An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100％in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3％)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3％,100.0％,100.0％,and 98.9％;these values were significantly higher than those of VIDAS CDAB(60.0％,98.9％,91.3％,and 92.7％)(Kappa=0.714,OR=157.50,95％CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective:To develop a method of employing flow cytometry to directly detect the γ-H2AX expression levels in peripheral blood lymphocytes of mice through fixation and lysis and to evaluate the feasibility of applying this method to research on the radiation-related biological effects and the efficacy evaluation of radioprotective drugs.Methods:A total of 41 male C57BL/6J mice were used. First, 21 mice were randomly divided into 7 groups according to different radiation doses (0, 1, 2, 4, 6, 8, and 10 Gy) with 3 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation and immediately fixed with formaldehyde. Red blood cells (RBC) were lysed with Triton X-100, and γ-H2AX was labeled with specific antibodies. DRAQ5 dye was used to further exclude debris and anucleate cells. The mean fluorescence intensity of γ-H2AX in lymphocyte populations was directly analyzed by flow cytometry through forward and side scatter, and dose-effect curves after irradiation were established. Then, the other 20 mice were divided into radiation alone groups and radiation combined with WR-2721 administration groups at 4 and 6 Gy, respectively, with 5 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation to detect the average fluorescence intensity of γ-H2AX in lymphocytes, which was used to evaluate the degree of DNA damage in mice and the therapeutic effect of WR-2721.Results:The expression of γ-H2AX in peripheral blood lymphocytes of mice significantly increased with the increase of radiation doses, and reached a peak at 1-2 h and then decreased. The dose-effect relationship was significant ( R2 = 0.9914). At 24 h after 4 and 6 Gy irradiation, compared with the radiation alone groups, the average fluorescence intensity of γ-H2AX in the radiation combined with WR-2721 administration groups was lower (144.8 ± 8.0 and 109.5 ± 9.7, vs. 178.0 ± 18.5 and 136.6 ± 5.4), with statistically significant difference ( t = 3.78, 5.48, P < 0.05). The average fluorescence intensity of γ-H2AX at 24 h after irradiation was consistent with the lowest values of the three blood cell lines at 7 or 14 d after irradiation. Conclusions:The application of flow cytometry with a fixation/dissolution protocol to directly detect the mean fluorescence intensity of γ-H2AX in peripheral blood lymphocytes of mice has significant application value in radiation biology effect research, radiation protection drug screening, and efficacy evaluation.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

This study investigated the mechanism of autophagy in the differentiation processes of MC3T3-E1 cells under osteogenic induction(physiological) and alcohol(AL) intervention(pathological), as well as the mechanism by which icariin(ICA) affected osteogenic differentiation of MC3T3-E1 cells under the pathological condition of AL intervention. Osteogenic mineralized nodule staining confirmed that the cells could differentiate into osteoblasts. After determining the appropriate concentrations of AL and ICA using the CCK-8 assay, seven groups were set up in this study: complete medium(CM) group, osteogenic induction medium(OIM) group, OIM+0.25 mol·L~(-1) AL group, OIM+0.25 mol·L~(-1) AL+1×10~(-8) mol·L~(-1) ICA group, OIM+0.25 mol·L~(-1) AL+1×10~(-7) mol·L~(-1) ICA group, OIM+0.25 mol·L~(-1) AL+1×10~(-6) mol·L~(-1) ICA group, and OIM+0.25 mol·L~(-1) AL+1×10~(-5) mol·L~(-1) ICA group, with a culture period of 7 days. Alkaline phosphatase(ALP) staining was used to detect the relative ALP area. Western blot and RT-qPCR were employed to analyze the expression of osteogenesis-and autophagy-related proteins and mRNAs. Reactive oxygen species(ROS) staining was used to detect ROS levels, and apoptosis was assessed through mitochondrial membrane potential assays. The results showed that ICA increased the relative ALP area that had been reduced by AL intervention. AL down-regulated the expression levels of Wnt family member 1(Wnt1), along with the osteogenesis-related mRNAs Wnt1, β-catenin, Runt-related transcription factor 2(Runx2), osteoprotegerin(OPG), and ALP, thereby inhibiting osteogenic differentiation. ICA up-regulated the expression levels of the osteogenesis-related proteins and mRNAs that had been inhibited by AL, promoting osteogenic differentiation. AL inhibited typical autophagy, while ICA regulated Rubicon to suppress LC3-associated phagocytosis(LAP) and promote typical autophagy. ICA also reduced the ROS levels that were elevated by AL and decreased the apoptosis of osteoblasts induced by AL intervention. In conclusion, ICA can regulate Rubicon to inhibit LAP, promote typical autophagy, eliminate ROS, reduce apoptosis, and ultimately enhance the osteogenic differentiation of MC3T3-E1 cells under the pathological condition of AL intervention by modulating the Wnt/β-catenin signaling pathway.
Autophagy/drug effects* ; Animals ; Osteogenesis/drug effects* ; Mice ; Cell Differentiation/drug effects* ; Osteoblasts/metabolism* ; Ethanol/pharmacology* ; Flavonoids/pharmacology* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Drugs, Chinese Herbal/pharmacology*