The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Diabetic nephropathy（DN） is a common and severe microvascular complication of diabetes. In recent years， the classical herbal formula Shenqi dihuang decoction has demonstrated unique advantages in the clinical treatment of DN. This article conducts a systematic review of the mechanisms of action and clinical applications of Shenqi dihuang decoction in the treatment of DN. It reveals that the mechanism by which this formula improves DN involves multi-target synergistic regulation. For instance, Shenqi dihuang decoction exerts multiple pharmacological effects by regulating signaling pathways including phosphatidy linostiol 3-kinase/protein kinase B， AMP-activated protein kinase/silent information regulator 1/forkhead box O1， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathways.These effects include regulating glucose and lipid metabolism， inhibiting oxidative stress， reducing inflammation， improving insulin resistance， modulating cell death （apoptosis/autophagy/ferroptosis/pyroptosis）， and preventing renal fibrosis. Existing clinical studies indicate that Shenqi dihuang decoction and its modified formulas， alone or in combination with other therapeutic methods， can significantly improve glucose and lipid metabolism， reduce proteinuria， and delay renal function decline in patients with DN. These effects are superior to those of Western medicines such as irbesartan， valsartan， and empagliflozin， and the treatment demonstrates good safety. Future research should leverage systems biology and artificial intelligence technologies to further elucidate the integrated mechanisms in the treatment of DN by Shenqi dihuang decoction， thereby advancing the precision and standardization of its clinical application.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Artery of Percheron(AOP)embolization or occlusion is a rare cerebrovascular disease that can lead to bilateral thalamic infarction with or without involvement of the upper midbrain.Due to its clinical rarity,lack of typical signs of cerebral infarction,and the diversity of patient symptoms,AOP occlusion-induced cerebral infarction is often misdiagnosed or overlooked,which delays the treatment.This article reported a case of a patient who presented with impaired consciousness as the primary symptom and was initially diagnosed with acute top-of-the-basilar artery embolism related cerebral infarction and underwent emergency endovascular thrombectomy,while the emergency angiography revealed an AOP occlusion.This article also analyzed the clinical features,diagnostic challenges,and treatment strategies of AOP occlusion in combination with the literature,with the aim of providing a reference for clinicians in the diagnosis and treatment of such cases.

Knee osteoarthritis(OA)is a primary cause of joint dysfunction.Knee osteotomy has garnered significant attention due to its potential to delay the progression of knee OA and enhance joint function.As a pivotal biomechanical factor in the onset and progression of OA,the accurate correction of abnormal knee alignment is the central objective of knee osteotomy.This article systematically reviews the biomechanical research progress related to knee osteotomy,with a focus on the precision and personalized correction of force line.The development of new classification system and measurement technology of force line is summarized,the biomechanical mechanism of knee OA induced by abnormal mechanical load is analyzed,and the goal of force line and clinical application progress of knee osteotomy is discusses,so as to provide a new perspective and idea for the clinical treatment of knee OA with knee osteotomy.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To explore the diagnostic value of serum C-reactive protein(CRP),serum amyloid A(SAA)and procalcitonin(PCT)combined with lactate dehydrogenase(LDH)and adenosine deaminase(ADA)in cerebrospinal fluid for elderly patients with central nervous system infection and their differential significance for different infection types.Methods A total of 97 elderly patients with central nervous system infection were enrolled as the infection group,including 31 cases with tuberculous meningitis(tuberculous meningitis group),36 cases with suppurative meningitis(suppurative meningitis group)and 30 cases with viral meningitis(viral meningitis group).A total of 97 patients with normal laboratory examination indexes who were treated due to primary headache during the same period were enrolled as the control group.The samples of fasting elbow venous blood were collected in the early morning of the next day after admission,and the serum was isolated to detect CRP and SAA levels.When consultation,lumbar puncture was performed to collect cerebrospinal fluid for the detection of LDH and ADA levels.The differences in above indexes were compared between groups,and diagnostic efficiency of each index and combined detection for central nervous system infection in elderly was analyzed by receiver operating characteristic(ROC)curves.Results The serum levels of CRP,SAA and PCT,and LDH and ADA in cerebrospinal fluid were higher in the infection group than those in the control group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)values of serum CRP,SAA and PCT,and cerebrospinal fluid LDH and ADA,and combined detection in the diagnosis of central nervous system infection were all>0.70(P＜0.05),showing good predictive efficiency and diagnostic efficiency,and the diagnostic efficacy of combined detection was the best.The cut-off values of serum CRP,SAA and PCT,cerebrospinal fluid LDH and ADA were 6.32 mg/L,33.86 mg/L,2.81 μg/L,33.53 U/L and 1.99 U/L,respectively.The serum levels of CRP,SAA and PCT were the highest in the suppurative meningitis group,while which were the lowest in the viral meningitis group.The cerebrospinal fluid levels of LDH and ADA were the highest in the tuberculous meningitis group,while which were the lowest in the viral meningitis group(P＜0.05).Conclusion The combined detection of serum CRP,SAA and cerebrospinal fluid PCT and LDH has certain diagnostic value for elderly central nervous system infection,which is beneficial to identify infection types.

Objective:To compare the embryo development potential and clinical outcomes between the patients with and without oocyte degeneration.Methods:This retrospective cohort study included a total of 242 cycles underwent ICSI that cultured in time-lapse incubator from January 2019 to June 2023 at the Reproductive and Genetic Center of Suzhou Municipal Hospital and all 3 119 oocytes were evaluated. Data collection continued to February 5th,2024 until the last birthing of the study. Patients were divided into degenerated group (140 cycles) and control group (102 cycles) according to whether oocyte degenerated after ICSI. Then the embryo developmental potential and clinical outcomes were compared. Furthermore, we also investigated whether embryo morphokinetics could be different between the two groups.Results:Female age, duration of infertility, body mass index, basal follicle sitmulating hormone, basal luteinizing hormone, basal estrogen (E 2), antral follicle count, anti-Müllerian hormone, factors of infertility and source of semen were similar between the two groups ( P>0.05). E 2 on human chorionic gonadotropin triggered day [2 513.00 (1 842.20, 3 638.50) ng/L], number of oocytes retrieved (13.56±4.80) and oocyte maturation rate [84.35% (1 601/1 898)] were significantly higher in degenerated group than those in control group [2 270.50 (1 472.00, 3 044.20) ng/L, P=0.019; 11.97±4.71, P=0.011; 81.08% (990/1 221), P=0.017], while normal fertilization rate [69.33% (1 103/1 591)], day 3 (D3) good-quality embryos [57.85% (634/1 096)], blastocyst formation rate [50.87% (469/922)] and embryo utilized rate [58.30% (643/1 103)] were significantly lower in degenerated group than those in control group [85.56% (847/990), P<0.001; 65.72% (556/846), P<0.001; 61.26% (446/728), P<0.001; 66.12% (560/847), P<0.001] . In addition, the proportion of low cell number (<7) of D3 embryos [33.76% (370/1 096)] and high fragmentation (fragmentation ≥50%, fragmentation 20%-50%) of D3 embryos [10.01% (109/1 089), 18.64% (203/1 089)] in degenerated group were significantly higher than those in control group [27.19% (230/846), P=0.002; 6.06% (51/841), P=0.002; 14.15% (119/841), P=0.009], and so were the incidence of DC1 and CC [5.98% (66/1 103) vs. 2.48% (21/847), P<0.001; 2.45% (27/1 103) vs. 0.94% (8/847), P=0.013]. As regard to the utilized embryos, there were no significant differences in t5, cc2, cc3 and s2 ( P>0.05), but tPNf [22.82(21.13, 24.84) h], t2 [25.37 (23.62, 27.37) h], t3 [35.64 (33.10, 38.03) h] and t4 [36.85 (34.70, 39.52) h] in degenerated group were significantly earlier than those in control group [23.04 (21.76, 25.41) h, P=0.001; 25.91 (24.15, 28.05) h, P=0.001; 36.16 (33.11, 38.81) h, P=0.040; 37.39 (35.11, 40.27) h, P=0.026]. Further more, after the first transfer of fresh or frozen embryos, there were no significant differences in clinical pregnancy rate, implantation rate, early abortion rate, live birth rate, sex ratio, preterm birth rate, low birth weight rate and birth defect rate between the two groups (all P>0.05). ICSI degeneration was not an independent factor of implantation rate, early abortion rate and live birth rate after ICSI treatment, but number of embryos transferred was an independent factor of implantation rate and live birth rate after ICSI treatment ( OR=2.806, 95% CI: 1.179-6.677, P=0.020; OR=2.622, 95% CI: 1.129-6.090, P=0.025). Conclusion:The presence of oocyte degeneration after ICSI may affect the overall developmental potential of its sibling oocytes and may also disturb the morphokinetics of the embyos, however the pregnancy outcomes and neonatal birth outcomes may not be affected if transfer the best embryo in the first fresh or frozen cycle.

Obsessive-compulsive disorder (OCD) is characterized by recurrent episodes of intrusive thinking and/or behavior, persistent and variable symptoms, and chronic recurrence. It is clearly recommended in the OCD treatment guidelines that psychotherapy can effectively improve clinical symptoms and play an important role in maintaining long-term efficacy. However, previous research and clinical practice paid little attention to the application of psychological interventions in OCD.Currently, there is insufficient understanding of psychotherapy for OCD, especially the proven first-line exposure and response prevention therapy (ERP), cognitive-behavioral therapy, and Morita therapy.Due to limited resources, they have not received effective intervention. Therefore, this article reviews the relevant research on psychological therapy intervention for OCD in recent years, summarizes the intervention effects of different psychological therapy methods on OCD and further elaborates on possible therapeutic mechanisms.Based on this, combined with the existing research, this article clarifies the effect of various behavioral psychological interventions and their combined treatment, and explores group and online forms of psychological intervention in order to increase the accessibility of psychotherapy for OCD patients.