Journal of the Chinese Medical Association : JCMA最新文献

Background: Controlled ovarian hyperstimulation (COH) is commonly used to obtain large numbers of high-quality oocytes. However, elevated estrogen levels due to COH can disrupt uterine fluid metabolism and impair embryonic implantation. We investigated the effects and mechanisms of Bushen Huoxue recipe (BSHX) on COH-induced impairment of endometrial receptivity.

Methods: Female mice were randomly divided into the following five groups: control, model, BSHX-L, BSHX-M, and BSHX-H. In addition to the control group, the COH model was established by injecting mice in the other groups with 0.4 IU/g pregnant mare serum gonadotropin and 1 IU/g human chorionic gonadotropin. After successful mating, mice in the BSHX-L, BSHX-M, and BSHX-H groups were treated with 5.5, 11.0, and 22.0 g/kg respectively. Mice in the control and model groups were administered distilled water (10 mL/kg) daily via gavage. Embryo numbers were examined on embryo day 10 (D10). Serum estradiol and progesterone levels were measured using an enzyme-linked immunosorbent assay on D4. Endometrial morphology was analyzed using hematoxylin-eosin staining. The protein and gene expression of leukemia inhibitory factor (LIF), cystic fibrosis transmembrane regulator (CFTR), and epithelial sodium channel (ENaC) subunits were assessed using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction.

Results: BSHX treatment reduced superphysiological serum estradiol and progesterone levels, improved endometrial morphology during the implantation window, upregulated LIF, α-, β-, and γ-ENaC expression, and downregulated CFTR expression, thereby enhancing embryo implantation.

Conclusion: BSHX may improve assisted reproductive technology pregnancy rates by regulating sex hormones and uterine fluid balance to prevent COH-induced endometrial damage.

Background: Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with few effective treatments. Although the KRAS gene has been implicated in the progression of thyroid cancer, its specific mechanism in ATC remains unclear. This study aims to reveal the impact of cancer-associated fibroblasts (CAFs) with KRAS overexpression on the malignant biological behavior of ATC.

Methods: The single-cell RNA sequencing (scRNA-seq) was used to analyze the KRAS expression profile of fibroblasts (Fibs) in ATC progression, including cell subpopulation identification, KRAS distribution across different cell types, and functional pathway enrichment. Paracancerous tissue fibroblasts (PTFs) and CAFs were co-cultivated with ATC cells, respectively, and were treated with KRAS inhibitor BI-2865. Western blot, colony formation assay, EdU staining, Transwell, and Annexin V-FITC/PI staining were used to analyze the effects of KRAS on the proliferation, migration, and invasion abilities of ATC cells, as well as its influence on downstream signaling pathways.

Results: In contrast to papillary thyroid cancer (PTC), the proportion of Fibs significantly increased in ATC, with KRAS observed to be highly expressed in Fibs. Further analysis revealed that Fib_KRAS+, which was highly expressed in ATC samples, did not show expression in PTC samples. In vitro cell experiments confirmed that CAFs with KRAS overexpression enhanced the proliferation, migration, and invasion of ATC cells and activated the downstream signaling pathway RAS/RAF/MAPK.

Conclusion: In summary, CAFs with KRAS overexpression play a crucial role in the malignant biological characteristics of ATC. Targeting KRAS may be a potential strategy to effectively curb the malignant progression of ATC.

Background: The clinical significance of programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC), particularly its association with platinum resistance (PR) and prognosis, remains unclear. This study aimed to evaluate the relationship between PD-L1 expression and PR in EOC and investigate cisplatin-induced PD-L1 modulation using in vitro and in vivo models.

Methods: We retrospectively analyzed 189 patients with EOC, treated between 2014 and 2020. Tumor PD-L1 expression was assessed by immunohistochemistry (IHC) using the combined positive score (CPS). Serum PD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Cisplatin-induced PD-L1 regulation was examined in paired platinum-sensitive (PS: A2780 and ES2) and PR (A2780R and ES2R) cell lines and xenograft models.

Results: High tumor PD-L1 expression (CPS ≥10) was more frequent in PR (38.5%) than in PS patients (19.0%, p < 0.01), and was associated with higher recurrence rates ( p < 0.001) and shorter overall survival ( p < 0.001). Serum PD-L1 concentrations were significantly elevated in patients with endometrioid and clear cell histologies compared with those in the control group ( p < 0.05). In vitro, PD-L1 expression was upregulated in PR cell lines compared with parental PS cell lines and was further increased following cisplatin exposure in a dose- and time-dependent manner. Xenograft models confirmed that cisplatin induces PD-L1 upregulation in both tumor tissue and serum, with more pronounced effects observed in PR tumors.

Conclusion: PD-L1 upregulation (CPS ≥10) is associated with PR, disease recurrence, and poor prognosis in EOC. Endometrioid and clear cell histologic subtypes demonstrated higher baseline PD-L1 expression in our cohort. Cisplatin-induced PD-L1 upregulation represents a tumor-intrinsic response, particularly in PR tumor cells, highlighting PD-L1 as a histology-specific marker of poor prognosis and a potential therapeutic target in platinum-resistant EOC.

Background: Single-large hepatocellular carcinoma (SLHCC) is defined as a solitary tumor that is >5 cm and lacks macrovascular invasion or extrahepatic spread. SLHCC is a distinct clinical subtype with considerable prognostic heterogeneity, and available staging systems offer limited predictive accuracy for this subgroup. Therefore, we aimed to develop a machine learning (ML)-based decision-tree model to improve individualized prognostic stratification of SLHCC.

Methods: This retrospective study included patients with SLHCC who were diagnosed at Taipei Veterans General Hospital between January 2012 and January 2023. The patients were randomly assigned to a training cohort and a validation cohort. Prognostic factors for overall survival (OS) were identified using multivariate Cox regression and incorporated into a decision-tree algorithm. The model performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUROC).

Results: Among the 477 patients, 307 (64.4%) received curative treatment, and 170 (35.6%) received non-curative therapy. The median age was 70 years, and 77.1% were male. After a median follow-up of 50 months, the 5-year OS rate was 42.0%. Six variables were independently associated with OS: tumor size >10 cm, serum creatinine >1 mg/dL, non-curative treatment, albumin-bilirubin (ALBI) grade 2, fibrosis-4 (FIB-4) score ≥2.67, and serum alpha-fetoprotein (AFP) >20 ng/mL. The decision-tree model incorporated four key variables: treatment modality, creatinine, tumor size, and FIB-4. The model stratified patients into five risk groups. The model's accuracy was 74.3% in the training cohort and 67.1% in the validation cohort, and the AUROCs were 0.756 and 0.706, respectively.

Conclusion: The clinically interpretable ML-based decision-tree model effectively stratifies patients with SLHCC according to prognosis using routine clinical and laboratory data. This model complements conventional staging systems and could support personalized treatment planning and patient counseling in real-world clinical practice.

Background: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).

Methods: This retrospective study included treatment-naïve nAMD patients who received three monthly intravitreal injections of 6.0 mg/0.05 ml faricimab or 2.0 mg/0.05 ml aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.

Results: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF, and IRF at 4 months ( p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 ( p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78 ± 0.47 to 0.66 ± 0.65 in the faricimab group compared to 0.78 ± 0.41 to 0.72 ± 0.60 in the aflibercept group ( p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs 91.9%, p = 0.016), SHRM (32.4% vs 59.5%, p = 0.022), and HRF (52.9% vs 89.2%, p = 0.001) at 4 months.

Conclusion: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.

Background: To provide an objective means of outcome assessment, we developed an innovative methodology to evaluate facial symmetry without defining an anatomical midsagittal plane. This study aimed to assess this novel methodology for evaluating zygomaticomaxillary complex (ZMC) symmetry.

Methods: Patients who underwent ZMC fracture reduction with available postoperative facial computerized tomography (CT) images were included in the study group. The control group comprised patients who underwent facial surgeries unrelated to ZMC fractures and had either pre- or postoperative facial CT images. Segmented 3D models reconstructed from CT images, including forehead and bilateral ZMCs, were mirrored, transposed, and analyzed using Hausdorff distance (HD) to quantify the maximum morphological and spatial deviation between the two sides. The 95th percentile HD values (HD95) were calculated to represent the top 95% of surface-to-surface distances between mirrored and contralateral ZMCs, serving as an objective measurement of symmetry.

Results: The study group included 21 patients (12 males, nine females), consisting of two with isolated ZMC arch fractures, 12 with ZMC complex fractures, and seven with ZMC fractures combined with orbital blow-out or Le Fort I fractures. The control group comprised 22 patients (13 males, nine females) without ZMC fractures, including six with mandible fractures, two with orbital floor blow-out fractures, 11 with parotid gland tumors, and three who had undergone rhinoplasty. The mean HD95 was significantly higher in the study group (3.48 ± 1.50 mm) compared with the control group (2.00 ± 0.76 mm) ( p = 0.0002).

Conclusion: This study demonstrated that the bilateral ZMC symmetry can be effectively and objectively assessed using a novel approach that combines mirroring, transposing, and HD analysis. This approach offers a quantitative tool that may enhance preoperative planning and postoperative evaluation.

Background: Mesalazine is a standard treatment for ulcerative colitis (UC). However, it is unclear whether the efficacy of mesalazine combined with traditional Chinese medicine (TCM) enemas is superior to that of mesalazine alone. Therefore, this study aimed to evaluate the clinical effectiveness of TCM enema hydrotherapy combined with mesalazine for active UC.

Methods: Patients with active UC were randomly assigned to two treatment groups: a combination of mesalazine and TCM enemas and mesalazine alone. Primary outcome measures included clinical effective and recurrence rate. Secondary outcomes included TCM symptom scores, levels of inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor α [TNF-α], high-sensitivity C-reactive protein [hs-CRP]), colonoscopy scores (Baron score), and disease activity indices (Sutherland Disease Activity Index [DAI], modified Mayo score).

Results: A total of 80 patients were included in the study. Regarding the primary outcomes, the total effective rate in the combination group was 95%, which was significantly higher than the 75% observed in the mesalazine group ( p = 0.012). The recurrence rate was lower in the combined group (2.5%) than in the mesalazine group (17.5%), but this difference did not reach statistical significance ( p = 0.062). Regarding secondary outcomes, the combination group showed higher reductions in TCM symptom scores than the mesalazine group, particularly in the areas of bloody stool ( p < 0.001), diarrhea ( p < 0.001), and abdominal pain ( p = 0.044). The combination group also showed significantly lower inflammatory markers (IL-8, TNF-α, hs-CRP) and disease activity scores (Baron score, DAI, modified Mayo score) compared with the mesalazine group ( p < 0.05).

Conclusion: The combination treatment may be more effective than mesalazine. The combination of TCM enema and mesalazine led to significant clinical improvement with lower inflammatory responses and reduced recurrence rates in patients with active UC.

Background: The surgical safety margin of the oral squamous cell carcinoma (OSCC) is not clear. We investigate the effect of nimotuzumab (N) combined with nab-paclitaxel, cisplatin, and fluorouracil (APF) neoadjuvant chemotherapy on the surgical margin.

Methods: This was a single-center retrospective study, included 18 to 75 ages diagnosed newly histologically confirmed OSCC patients at the Fourth Hospital of Hebei Medical University between September 2019 and December 2021. Patients were divided into neoadjuvant chemotherapy and surgery group (G1 group, N + APF), chemotherapy and surgery group (G2 group, APF alone), and surgery group (G3 group). Tissue samples of the tumor core zone (P0), adjacent (P1, 3-5 mm from tumor), distal adjacent (P2, 7-10 mm from tumor), and surgical margin (P3, 15 mm from tumor) were collected. The main indicators of pathological evaluation were pathologic complete response (pCR) and major pathologic response (MPR). Chi-square or Fisher test was used for the pathological response rate of qualitative data, and t test or analysis of variance (ANOVA) was used for protein expression changes of quantitative data. A threshold value of p < 0.05 indicated statistical significance.

Results: In the G1 (n = 15) and G2 (n = 20) groups, various degrees of degeneration and necrosis were observed in the tumor retraction area. Nine cases of MPR and four cases of pCR in the G1 group; eight cases of MPR and three cases of pCR in the G2 group. The expressions of p53, eIF4E, and EGFR in the samples of the three groups decreased from P0 to P2 ( p < 0.05). In the molecular tumor shrinkage area, the expression levels of p53, eIF4E, and EGFR in the shrinkage zone were lower than those in the negative margin.

Conclusion: There is no significant statistical difference between APF plus nimotuzumab or APF alone in the pathological remission rate. The surgical margin was defined to 1.5 cm clinical margin after tumor regression.