POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

AIM: To investigate the characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma(PACG).METHODS: A total of 48 first-degree relatives of PACG patients aged 40-60 who were treated in the Affiliated Eye Hospital of Nanchang University from September 2020 to October 2022 were selected as the observation group. Additionally, 40 cases(40 eyes)of healthy individuals without glaucoma and family history of glaucoma at the same age group were collected as the control group. They were divided into younger group(40-49 years old)and elder group(50-60 years old). All subjects were examined with ultrasound biomicroscopy(UBM)and were measured using camera measure software. The parameters mainly included anterior chamber depth(ACD), anterior chamber area(ACA), anterior chamber width(ACW), anterior segment depth(ASD), angle open distance(AOD500), trabecular iris angle(TIA), trabecular iris area(TISA500), lens vault(LV), iris curve(IC), iris thickness(IT500), scleral ciliary process angle(SCPA), and iris ciliary process distance(ICPD).RESULTS: ACD, ACA, AOD500, TISA500 and TIA in the observation group were lower than those of the control group, and LV and IC were higher than those of the control group(all P<0.05). ACD, ACA, AOD500, TISA500, and TIA of the elder group were lower than those in the age-matched control group, while LV and IC were larger than those of the age-matched control group(all P<0.05). ACD, AOD500, TISA500, and TIA of the younger observation group were smaller than those of the age-matched control group, but LV and IC were significantly larger than those of the age-matched control group(all P<0.05). ACD, ACA, AOD500, TISA500 and TIA of the elder observation group were significantly lower than those of the younger observation group, and LV and IC were significantly larger than those of the younger observation group(all P<0.05). There was a difference in the distribution of ACD between the observation group and the control group(P<0.05), and the proportion of moderate to severe shallow anterior chambers was 10 times that of the control group. Correlation analysis showed that TISA500 was positively correlated with ACD and ACA, and negatively correlated with LV and IC, and TISA500 was mainly influenced by LV. IC had a positive correlation with LV and a negative correlation with ACD and ACA.CONCLUSION: First-degree relatives of PACG with normal axial length have a high risk of angle closure. The anterior segment structures of first-degree relatives of PACG are more crowded than normal individuals, and the lens forward shift may be the initial influencing factor for narrow angle.

Chronic obstructive pulmonary disease(COPD)poses a serious threat to human health and carries a heavy burden of disease.The disease burden mainly includes traditional epidemiological indicators such as morbidity,disability rate,and mortality rate,as well as economic burden evaluation indicators such as direct economic burden,indirect economic burden,and intangible economic burden,as well as social/health burden evaluation indicators such as potential years of life reduction,disability adjusted life years,and quality adjusted life years.It summarized the existing methods for evaluating the burden of COPD diseases and proposed the following suggestions:(1)enriching economic burden research methods to comprehensively and accurately evaluate direct economic burden;(2)expanding the scope of economic burden research and improve the economic burden research of COPD;(3)strengthening information management and enhance the accuracy of disease burden data;(4)exploring multidimensional indicators and establish a COPD disease burden evaluation system;(5)strengthening relevant research and highlight the health economics advantages of traditional Chinese medicine intervention in COPD.It can provide references for establishing a COPD disease burden evaluation system and policy formulation.

Objective:To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.