Tumor burden score is superior to primary liver cancer stages in predicting prognosis for patients with combined hepatocellular-cholangiocarcinoma after surgery: A multi-center study.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial. METHODS: Patients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation. RESULTS: A total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results. CONCLUSIONS: TBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions.

Determining priority control factors for heavy metal management in urban road dust based on source-oriented probabilistic ecological-health risk assessment: A study in Xi'an during peak pollution season.

Urban road dust (URD) is essential for transporting heavy metals (HMs), which can be a major danger to both the environment and human health. Moreover, URD has the potential to be carried into bodies of water, leading to contamination of the aquatic ecosystem. A study was conducted in Xi'an, a city in northwestern China known for high air pollution levels, during January 2024 - a period characterized by peak pollution due to frequent low wind speeds and temperature inversions. The research investigated the presence of 10 types of HMs (Cu, Zn, Cd, Cr, Pb, As, Ni, Hg, Co, and Mn) in URD. Findings revealed elevated levels of Cu, Zn, Cd, Cr, Pb, As, and Hg in URD compared to background levels. Hg showed the most significant contamination (moderate to heavy), followed by moderate contamination of Cd, and lower levels of As, Zn, and Cu. The main sources of HMs were traffic (58.2%), mixed natural and industrial (30.3%), and industrial (11.5%). The ecological risk in the area was deemed to be very high, primarily because of Hg and Cd. Based on probabilistic health risk assessments, it was determined that non-carcinogenic risks were deemed acceptable for all groups. Nevertheless, the possibility of carcinogenic risks should not be disregarded. Strategies for controlling ecological-health risks prioritize mixed natural and industrial sources, with a focus on Hg, Cd, and As in URD. The results offer a foundation for policymakers to create specific control strategies.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

PARG Promotes Esophagus Cancer Cell Metastasis by Activation of the Wnt/ß-Catenin Pathway.

Esophagus cancer (EC) is a highly malignant and metastatic cancer. Poly(ADP-ribose) glycohydrolase (PARG), a DNA replication and repair regulator, inhibits cancer cell replication defects. This study aimed to explore the role of PARG in EC. The biological behaviors were analyzed using MTT assay, Transwell assay, scratch test, cell adhesion assay, and western blot. PARG expression was detected using quantitative PCR and immunohistochemical assay. The regulation of the Wnt/ß-catenin pathway was assessed using western blot. The results showed that PARG was highly expressed in EC tissues and cells. Knockdown of PARG suppressed cell viability, invasion, migration, adhesion, and epithelial-mesenchymal transition. Conversely, overexpression of PARG promoted the biological behaviors mentioned above. Moreover, overexpression of PARG promoted the activation of the Wnt/ß-catenin pathway rather than the STAT and Notch pathways. XAV939, the Wnt/ß-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/ß-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.

Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists for renal outcomes: A systematic review and meta-analysis.

BACKGROUND: Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) are noted for their potential cardiorenal benefits for patients with type 2 diabetes mellitus and chronic kidney diseases; however, the effect of this regimen on renal outcomes remains uncertain. METHODS: We performed a systematic review and meta-analysis of nonsteroidal MRAs focusing primarily on renal outcomes and safety in randomized, controlled trials. The MEDLINE, Embase, and Cochrane databases were systemically searched for trials published through April 2022. We included randomized, controlled trials assessing the effects of nonsteroidal MRAs on renal outcomes, as well as cardiovascular disease (CVD) effects in patients with chronic kidney disease (CKD). Summary estimates of risk ratios (RRs) reductions were calculated with a random-effects model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO under number CRD42022335464. FINDINGS: In total, 11 trials and 1 pooled analysis including a total of 17,517 participants were enrolled. Nonsteroidal MRAs reduced renal composite endpoints by 17 % [HR = 0.83, 95 % (0.75, 0.91); low quality] with 16 % in kidney failure (high quality), 23 % in ESRD (high quality), 20 % in eGFR decreased to less than 15 mL/min/1.73 m2 (high quality), and 17 % with more than a 40 % decrease in eGFR (high quality); 14 % with cardiovascular composite endpoints [HR = 0.86, 95 % (0.78, 0.94); moderate quality]; and 13 % of all-cause mortality [HR = 0.87, 95 % (0.76, 0.98); moderate quality]. Nonsteroidal MRAs were also associated with additional benefits in lowering UACR levels (moderate quality) and lowering BP levels (moderate quality) compared with the control groups. However, nonsteroidal MRAs did not show a statistically significant effect on the risk of renal death (moderate quality), hospitalization for any cause (moderate quality) or change in GFR (low quality). Regarding safety, there was no significant difference in the risk of adverse events between the participants receiving nonsteroidal MRAs and the control group. INTERPRETATION: Nonsteroidal MRAs had a statistically beneficial effect on reducing the risk of the composite kidney outcome, the composite of cardiovascular outcomes, and all-cause mortality. Nonsteroidal MRAs were also associated with benefits of proteinuria remission and blood pressure lowering. Although these findings provided positive evidence for the use of nonsteroidal MRAs for cardiorenal protection in patients with or without CKD, the quality of this evidence is potentially uncertain.

Insight into the Prospects for Tumor Therapy Based on Photodynamic Immunotherapy.

Malignancy is one of the common diseases with high mortality worldwide and the most important obstacle to improving the overall life expectancy of the population in the 21st century. Currently, single or combined treatments, including surgery, chemotherapy, and radiotherapy, are still the mainstream regimens for tumor treatment, but they all present significant side effects on normal tissues and organs, such as organ hypofunction, energy metabolism disorders, and various concurrent diseases. Based on this, theranostic measures for the highly selective killing of tumor cells have always been a hot area in cancer-related fields, among which photodynamic therapy (PDT) is expected to be an ideal candidate for practical clinical application due to its precise targeting and excellent safety performance, so-called PDT refers to a therapeutic method mainly composed of photosensitizers (PSs), laser light, and reactive oxygen species (ROS). Photoimmunotherapy (PIT), a combination of PDT and immunotherapy, can induce systemic antitumor immune responses and inhibit continuing growth and distant metastasis of residual tumor cells, demonstrating a promising application prospect. This article reviews the types of immune responses that occur in the host after PDT treatment, including innate and adaptive immunity. To further help PIT-related drugs improve their pharmacokinetic properties and bioavailability, we highlight the potential improvement of photodynamic immunotherapy from three aspects: immunostimulatory agents, tumor-associated antigens (TAAs) as well as different immune cells. Finally, we focus on recent advances in various strategies and shed light on their corresponding mechanisms of immune activation and possible clinical applications such as cancer vaccines. Having discovered the inherent potential of PDT and the mechanisms that PDT triggers host immune responses, a variety of immunotherapeutic strategies have been investigated in parallel with approaches to improve PDT efficiency. However, it remains to be further elucidated under what conditions the immune effect induced by PDT can achieve tumor immunosuppression and to what extent PDT-induced antitumor immunity will lead to complete tumor rejection. Currently, PIT presents several outstanding intractable challenges, such as the aggregation ability of PSs locally in tumors, deep tissue penetration ability of laser light, immune escape, and biological toxicity, and it is hoped that these issues raised will help to point out the direction of preclinical research on PIT and accelerate its transition to clinical practice.

One-year follow-up study after patients with severe COVID-19 received human umbilical cord mesenchymal stem cells treatment.

BACKGROUND: The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19. OBJECTIVES: The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy. METHODS: Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George's Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs). MEASUREMENTS AND MAIN RESULTS: Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge. CONCLUSIONS: Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.

Alleviation of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma and its relationship with expression and changes of PD-L1.

The alleviation of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT) was compared for esophageal squamous cell carcinoma (ESCC), and the correlation between the expression and changes of PD-L1 and the efficacy of NICT was evaluated in this study. Fourteen patients with ESCC who received preoperative NICT were included in group A, and fourteen patients with ESCC who received preoperative NCRT were included in group B. Next, group A was divided into CR (complete response), PR (partial response), and NR (no response) according to the degree of pathological response. Also, the expression and changes of PD-L1 (CPS, TPS, IPS) before and after treatment were compared between the groups. We observed that after the treatment, the expression of PD-L1 in both groups was higher than before treatment. In group B, the expression of PD-L1 was elevated in 92.8% of patients, which was higher than that in group A, which had significantly increased IPS (p<0.05). In group A, 9 (64.2%) patients with CPS <10 achieved partial or complete response. There was no significant difference in pathological response and reduction of tumor thickness between the two groups or significant differences in CPS and TPS among CR, PR, and NR groups before treatment. The IPS was the highest in the CR group; however, the difference was not statistically significant. The differences in IPS change were significant among the three groups (p<0.05). In conclusion, NICT and NCRT could upregulate the expression of PD-L1. NCRT more significantly upregulated the expression of PD-L1, mainly of PD-L1 in immune cells in the tumor microenvironment. NICT was not less effective than NCRT in pathological response and tumor thickness changes. The preoperative CPS and TPS scores of PD-L1 did not effectively predict the degree of pathological response, but the high IPS and high IPS downregulation could be related to the degree of pathological response. Some patients with low preoperative expression of PD-L1 could still achieve a good response by NICT. As NCRT can upregulate the expression of PD-L1, the low preoperative expression of PD-L1 is no contraindication for immunotherapy, which provides a new basis and prognostic indexes for chemoradiotherapy combined with immunotherapy.

Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS: In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS: Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). CONCLUSIONS: The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. CLINICAL TRIAL REGISTRATION: NCT04177797.

Native T1 Mapping in Assessing Kidney Fibrosis for Patients With Chronic Glomerulonephritis.

Purpose: To assess the utility of non-contrast enhanced native T1 mapping of the renal cortex in assessing renal fibrosis for patients with chronic glomerulonephritis (CGN). Methods: A total of 119 patients with CGN and 19 healthy volunteers (HVs) were recruited for this study. Among these patients, 43 had undergone kidney biopsy measurements. Clinical information and biopsy pathological scores were collected. According to the results of the renal biopsy, the patients were classified into the high (25-50%), low (<25%) and no renal interstitial fibrosis (IF) (0%) groups. The correlations between the T1 value in the renal cortex and each of the clinical parameters were separately analyzed. The relationships between each fibrosis group and the T1 value were also evaluated and compared between groups. Binary logistic regression analysis was further used to determine the relationship between the T1 value and renal fibrosis. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of the T1 value for renal fibrosis. Results: Compared with those of the HVs, the T1 values were significantly higher in patients at all stages of chronic kidney disease (CKD) (all p < 0.05). Significant T1 differences were also revealed between patients with different stages of CKD (p < 0.05). Additionally, the T1 value correlated well with CKD stage (p < 0.05), except between CKD 2 and 3. In addition, the T1 value was positively correlated with cystatin C, neutrophil gelatinase-associated lipocalin, and serum creatinine and negatively correlated with hemoglobin, kidney length, estimated glomerular filtration rate and hematocrit (all p < 0.05). Compared with those of the no IF group, the T1 values were increased in the low- and high-IF groups (both p < 0.05). Logistic regression analysis showed that an elevated T1 value was an independent risk factor for renal fibrosis. ROC analysis suggested that the optimal critical value of T1 for predicting renal fibrosis was 1,695 ms, with a specificity of 0.778 and a sensitivity of 0.625. Conclusion: Native T1 mapping demonstrated good diagnostic performance in evaluating renal function and was an effective noninvasive method for detecting renal fibrosis in CGN patients.

Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT. METHODS: All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status. RESULTS: Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall's tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05). CONCLUSIONS: Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.

Human Umbilical Cord Mesenchymal Stromal Cell Treatment of Severe COVID-19 Patients: A 3-Month Follow-Up Study Following Hospital Discharge.

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% ± 8.46% and 59.45% ± 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% ± 8.00% and 58.97% ± 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 ± 3.69 vs. 31.9 ± 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 ± 0.88 vs. 1.00 ± 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

Application of phototherapeutic-based nanoparticles in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death, which accounts for approximately 10% of all new cancer cases worldwide. Surgery is the main method for treatment of early-stage CRC. However, it is not effective for most metastatic tumors, and new treatment and diagnosis strategies need to be developed. Photosensitizers (PSs) play an important role in the treatment of CRC. Phototherapy also has a broad prospect in the treatment of CRC because of its low invasiveness and low toxicity. However, most PSs are associated with limitations including poor solubility, poor selectivity and high toxicity. The application of nanomaterials in PSs has added many advantages, including increased solubility, bioavailability, targeting, stability and low toxicity. In this review, based on phototherapy, we discuss the characteristics and development progress of PSs, the targeting of PSs at organ, cell and molecular levels, and the current methods of optimizing PSs, especially the application of nanoparticles as carriers in CRC. We introduce the photosensitizer (PS) targeting process in photodynamic therapy (PDT), the damage mechanism of PDT, and the application of classic PS in CRC. The action process and damage mechanism of photothermal therapy (PTT) and the types of ablation agents. In addition, we present the imaging examination and the application of PDT / PTT in tumor, including (fluorescence imaging, photoacoustic imaging, nuclear magnetic resonance imaging, nuclear imaging) to provide the basis for the early diagnosis of CRC. Notably, single phototherapy has several limitations in vivo, especially for deep tumors. Here, we discuss the advantages of the combination therapy of PDT and PTT compared with the single therapy. At the same time, this review summarizes the clinical application of PS in CRC. Although a variety of nanomaterials are in the research and development stage, few of them are actually on the market, they will show great advantages in the treatment of CRC in the near future.

Chinese herbal medicines for the treatment of cough in idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and hidden onset, which causes major health problems worldwide. Cough is a typical manifestation of IPF, which is usually characterized by cough without phlegm, and seriously affects the quality of life (QOL) of patients. At present, the treatment of IPF is mainly focused on prolonging survival time and improving lung function, such as pirfenidone, nintedanib, and N-acetylcysteine (NAC), but lack of effective measures to improve the QOL. Chinese herbal medicines (CHMs) is widely used in the clinical treatment of IPF. The adjuvant treatment of CHMs can effectively reduce the clinical symptoms of patients. Therefore, we designed this study to evaluate the role of CHMs in the treatment of cough in IPF. METHOD: This systematic review and meta-analysis will extract all randomized controlled trials (RCTs) related to the treatment of IPF from the following electronic database without date or language restrictions: PubMed, EMBASE, Cochrane CENTRAL, CNKI, VIP, CBM, and Wanfang database. The primary outcomes will be cough frequency and QOL, while secondary outcomes will include safety events. The methodologic quality of RCTs will be assessed using the Cochrane risk assessment tool. The I test will be used to identify the extent of heterogeneity, and funnel plot analysis will be used to test the publication deviation (the number of studies included >10). We will use RevMan5.3 software for data synthesis and analysis. RESULT: This review evaluates the efficacy and safety of CHMs in combination therapy on cough frequency, the quality of life, adverse reactions and safety incidents in patients with IPF. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of CHMs in combination with conventional therapy in treatment of cough in IPF. OSF REGISTRATION DOI: 10.17605/OSF.IO/JKQYV.

Prognostic effect of pretreatment albumin-to-alkaline phosphatase ratio in human cancers: A meta-analysis.

PURPOSE: It has been demonstrated that, for various types of cancer, the pretreatment albumin/alkaline phosphatase ratio (AAPR) was a prognostic factor. Therefore, in order to determine AAPR's prognostic effect on cancer, the meta-analysis was hereby performed. PATIENTS AND METHODS: The relevant studies conducted before November 10, 2019, were comprehensively searched in Web of Science, PubMed, and Embase. HRs(hazard ratios) with related 95%CIs(confidence intervals) were adopted to estimate AAPR's prognostic impact on overall survival (OS) & disease-free survival (DFS). RESULTS: Our meta-analysis involved thirteen cohort studies, which included 5,204 cases of 8 types. The results of this meta-analysis indicated that higher AAPR was corrected with better OS (pooled HR = 0.52; 95%CI = 0.47-0.58; P<0.001) and DFS (pooled HR = 0.55; 95%CI = 0.47-0.66; P<0.001). Subgroup analysis on OS was based on the cancer system, treatment methods, and cutoff value. Moreover, higher AAPR was statistically in associated with lighter infiltration (pooled OR = 0.79; 95%CI = 0.73-0.85; P<0.001), no lymph nodes metastasis (pooled OR = 0.89; 95%CI = 0.83-0.95; P = 0.001), and no distant metastasis (pooled OR = 0.92; 95%CI = 0.86-0.99; P = 0.028). CONCLUSION: Higher AAPR was related to better prognosis of cancer, and in cancer therapy, AAPR could be taken as a promising marker of prognosis. It might help physicians to select the most appropriate treatments by evaluating the current status of patients with cancer. Future multicenter prospective clinical trials were required to verify its applications.

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.

Relationship and prognostic significance between preoperative serum albumin to globulin ratio and CT features of non-small cell lung cancer.

PURPOSE: This study was conducted to assess the relationship and prognostic significance between preoperative serum albumin to globulin ratio (AGR) and high-resolution computed tomography (HRCT) features of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Demographic parameters, laboratory values including AGR and other clinical variables were evaluated in 180 patients with NSCLC, and 72 of these patients had results of radiology parameters detected with HRCT [including emphysema, tumor disappearance rate (TDR), CT values and CT enhanced values of the tumor mass] were assessed for survival analyses. The 72 patients were divided into two groups: normal lung group and emphysema group. The discriminatory values for AGR between these two groups were assessed by Mann-Whitney U test The relationship between TDR and AGR in NSCLC patients was evaluated by Pearson correlation analysis. RESULTS: In multivariate analysis, TDR (p = 0.033), AGR (p = 0.038), emphysema (p = 0.009), and N stage (P = 0.026) were independent predictors of overall survival (OS). AGR was higher in NSCLC patients without emphysema than NSCLC patients with emphysema (z = -2.979, P = 0.003). TDR demonstrated that there was a positive relationship with AGR (r = 0.307, p = 0.009). A nomogram with AGR, TDR, emphysema, and N stage was established to predict 5-year survival. CONCLUSIONS: There is a relationship between CT features and AGR in NSCLC. The integrative nomogram combined with CT images, clinical and hematologic features improved survival prediction in NSCLC patients, which offers a non-invasive, comprehensive, and convenient evaluation for individualized management of NSCLC patients.