BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I²=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I²=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).
Humans ; Neuralgia, Postherpetic/therapy* ; Acupuncture Therapy/methods* ; Systematic Reviews as Topic

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To analyze the basic conditions and pathological characteristics of the samples in the Human Brain Bank of Hebei Medical University,which were pathologically diagnosed as cerebral amyloid angiopathy,and to provide reference for the research of related diseases.Methods The basic data of gender,age,apolipoprotein E genotype,pathological classification of cerebral amyloid angiopathy,Alzheimer's disease-related pathological change score,comorbidities and other pathological information were analyzed.Results Up to October 2024,twenty samples were confirmed by pathological diagnosis,with a male to female ratio of 3:1 and an average age of(80.90±8.08)years.Involve three kinds of apolipoprotein E subtype,5 kinds of genotypes(ε2/ε3 xε2/ε4、ε3/ε3 xε3/ε4、ε4/ε4);There were 2 pathologic types,including 6 cases of type 1 and 14 cases of type 2.The pathological grade included 3 grades.The severity grade and subtype classification of cerebral amyloid vascular disease were correlated with the degree of pathological changes of Alzheimer's disease.Cerebral amyloid angiopathy samples could coexist with other degenerative diseases with high comorbidity.Conclusion The incidence of cerebral amyloid angiopathy is higher in the aged samples collected based on Brain Bank,which coexists with conditions such as Alzheimer's disease and microbleeds,etc.It provides more detailed pathological diagnosis basis for further scientific research sharing of samples.

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*