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BackgroundProgression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction.MethodsThis study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital.ResultsThe multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P

IntroductionA number of evidences have proved that “Nostoc commune” Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of “Nostoc commune” Vauch extracellular matrix– a water-stress protein (WSP) still needs to be elucidated.MethodsIn our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment.ResultsWe found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells.DiscussionGiven the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

BackgroundCharacterization of gene mutation profiles can provide new treatment options for patients with diffuse large B-cell lymphoma (DLBCL). However, this method is challenged by the limited source of tissue specimens, especially those of DLBCL patients at advanced stages. Therefore, in the current study, we aimed to describe the gene mutation landscape of DLBCL using circulating tumor DNA (ctDNA) samples obtained from patients’ blood samples, as well as to explore the relationship between ctDNA mutations and the prognosis and treatment response of patients with newly diagnosed DLBCL.MethodsA total of 169 newly diagnosed Chinese DLBCL patients were included in this study, among which 85 patients were divided into a training set and 84 were assigned into a validation set. The mutation profile of a 59-gene panel was analyzed by targeted next generation sequencing (NGS) of the patients’ ctDNA samples. Differences in clinical factors between patients with and without ctDNA mutations were analyzed. In addition, we also explored gene mutation frequencies between GCB and non-GCB subtypes, and the relationship between gene mutation status, clinical factors, mean VAF (variant allele frequencies) and the patients’ overall survival (OS) and progression-free survival (PFS).ResultsctDNA mutations were detected in 64 (75.3%) patients of the training set and 67 (79.8%) patients of the validation set. The most commonly mutated genes in both sets were PCLO, PIM1, MYD88, TP53, KMT2D, CD79B, HIST1H1E and LRP1B, with mutation frequencies of >10%. Patients with detectable ctDNA mutations trended to present advanced Ann Arbor stages (III-IV), elevated LDH (lactate dehydrogenase) levels, shorter OS and PFS, and a lower complete response (CR) rate to the R-CHOP regimen compared with DLBCL patients without ctDNA mutations. In addition, mean VAF (≥4.94%) and PCLO mutations were associated with poor OS and PFS.ConclusionWe investigated the ctDNA mutation landscape in Chinese patients with newly diagnosed DLBCL and found that ctDNA could reflect tumor burden and patients with detectable ctDNA mutations trended to have shorter OS and PFS and a lower CR rate.

ObjectivesInterstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine and prednisone)-like chemotherapy, negatively affected patients’ clinical outcome and quality of life. We aimed to explore patient-related, disease-related and drug-related risk factors associated with IP and gain a better understanding of the incidence in NHL patients.MethodsDatabases, including PubMed, Ovid, China National Knowledge Internet (CNKI), and Wanfang Database from inception to January 20, 2022, were searched to identify studies evaluating the risk factors and incidence of IP. The included studies were assessed by Newcastle-Ottawa Quality Scale and above 7 points was considered high quality. The statistical analysis of risk factors was assessed by RevMan software (version 5.3) and incidence of IP was calculated by R software (version 4.1.2). Fixed-or random-effects models were applied to estimated the relative risks (RRs) and 95% confidence interval (Cl).ResultsA total of 12 studies comprised of 3423 NHL patients were included in the analysis. Among the 3 available patient-related risk factors, 6 disease-related risk factors and 3 drug-related risk factors, it was found that only drug-related risk factors were significantly associated with IP development: pegylated liposomes doxorubicin (PLD) replacement (RR = 3.25, 95% CI = 1.69-6.27, I2 =64%), rituximab (RTX) addition (RR = 4.24, 95% CI = 2.58-6.96, I2 =0) and granulocyte colony stimulating factor (G-CSF) administration (RR = 5.80, 95% CI = 3.05-11.05, I2 =0). The pooled incidence of CHOP, R-CHOP, and R-CDOP regimen was 1.0% (95% CI 0.00-0.01, I2 = 8%), 7.0% (95% CI 0.05-0.09, I2 = 64%) and 22.0% (95% CI 0.13-0.32, I2 = 87%) respectively.ConclusionPLD replacement, RTX addition and G-CSF administration were significant risk factors of IP for NHL patients received the CHOP-like chemotherapy. Clinicians should focus on these patients to detect and treat the IP development timely, which might bring benefit in patients’ survival.Systematic Review RegistrationPROSPERO, identifier CRD42022309884.

PurposeAlthough the role of tumor-infiltrating T cells in follicular lymphoma (FL) has been reported previously, the prognostic value of peripheral blood T lymphocyte subsets has not been systematically assessed. Thus, we aim to incorporate T-cell subsets with clinical features to develop a predictive model of clinical outcome.MethodsWe retrospectively screened a total of 1,008 patients, including 252 newly diagnosed de novo FL patients with available peripheral blood T lymphocyte subsets who were randomized to different sets (177 in the training set and 75 in the internal validation set). A nomogram and a novel immune-clinical prognostic index (ICPI) were established according to multivariate Cox regression analysis for progression-free survival (PFS). The concordance index (C-index), Akaike’s information criterion (AIC), and likelihood ratio chi-square were employed to compare the ICPI’s discriminatory capability and homogeneity to that of FLIPI, FLIPI2, and PRIMA-PI. Additional external validation was performed using a dataset (n = 157) from other four centers.ResultsIn the training set, multivariate analysis identified five independent prognostic factors (Stage III/IV disease, elevated lactate dehydrogenase (LDH), Hb 36.6%) for PFS. A novel ICPI was established according to the number of risk factors and stratify patients into 3 risk groups: high, intermediate, and low-risk with 4-5, 2-3, 0-1 risk factors respectively. The hazard ratios for patients in the high and intermediate-risk groups than those in the low-risk were 27.640 and 2.758. The ICPI could stratify patients into different risk groups both in the training set (P < 0.0001), internal validation set (P = 0.0039) and external validation set (P = 0.04). Moreover, in patients treated with RCHOP-like therapy, the ICPI was also predictive (P < 0.0001). In comparison to FLIPI, FLIPI2, and PRIMA-PI (C-index, 0.613-0.647), the ICPI offered adequate discrimination capability with C-index values of 0.679. Additionally, it exhibits good performance based on the lowest AIC and highest likelihood ratio chi-square score.ConclusionsThe ICPI is a novel predictive model with improved prognostic performance for patients with de novo FL treated with R-CHOP/CHOP chemotherapy. It is capable to be used in routine practice and guides individualized precision therapy.

BackgroundTypical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL.MethodsA total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7–14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation.ResultsThree months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms.ConclusionALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.

BackgroundPost-molar gestational trophoblastic neoplasia (pGTN) develops in about 15% to 20% of complete hydatidiform mole (CMH). Commonly, pGTN is diagnosed based on hCG monitoring following the molar evacuation. To date, no detailed information is available on how fast can pGTN develop from CHM. However, the concurrence of CHM and pGTN is extremely rare.Case presentationA 29-year-old woman presented to the gynecology department with irregular vaginal bleeding and an elevated hCG serum level. Both ultrasound and MRI showed heterogeneous mass in uterine cavity and myometrium. Suction evacuation was performed and histologic examination of the evacuated specimen confirmed complete hydatidiform mole. Repeated ultrasound showed significant enlargement of the myometrium mass one week after the evacuation. pGTN with prognostic score of 4 was then diagnosed and multi-agent chemotherapy regimen implemented with a good prognosis.ConclusionIn rare cases, CMH can rapidly progress into pGTN. Imaging in combination with hCG surveillance seems to play a vital role guiding timely diagnosis and treatment in the specific condition. Low-risk gestational trophoblastic neoplasia (GTN) should be managed stratified according to the individual situation.