Reconstitution of peripheral blood T cell receptor ß immune repertoire in immune checkpoint inhibitors associated myocarditis.

PURPOSE: Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis. METHODS: A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood. RESULTS: In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments. CONCLUSION: The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-ß-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

LINC00963 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma by Interacting with miR-10a to Upregulate SKA1 Expression.

Long non-coding RNA (lncRNA) is associated with a large number of tumor cellular functions together with chemotherapy resistance in a variety of tumors. LINC00963 was identified to regulate the malignant progression of various cancers. However, whether LINC00963 affects drug resistence in esophageal squamous cell carcinoma (ESCC) and the relevant molecular mechanisms have never been reported. This study aims to investigate the effect of LINC00963 on cisplatin resistance in ESCC. After detecting the level of LINC00963 in human esophageal squamous epithelial cells (HET-1 A), ESCC cells (TE-1) and cisplatin resistant cells of ESCC (TE-1/DDP), TE-1/DDP cell line and nude mouse model that interfered with LINC00963 expression were established. Then, the interaction among LINC00963, miR-10a, and SKA1 was clarified by double luciferase and RNA immunoprecipitation (RIP) assays. Meanwhile, the biological behavior changes of TE-1/DDP cells with miR-10a overexpression or SKA1 silencing were observed by CCK-8, flow cytometry, scratch, Transwell, and colony formation tests. Finally, the biological function of the LINC00963/SKA1 axis was elucidated by rescue experiments. LINC00963 was upregulated in TE-1 and TE-1/DDP cell lines. LINC00963 knockdown inhibited SKA1 expression of both cells and impaired tumorigenicity. Moreover, LINC00963 has a target relationship with miR-10a, and SKA1 is a target gene of miR-10a. MiR-10a overexpression or SKA1 silencing decreased the biological activity of TE-1/DDP cells and the expression of SKA1. Furthermore, SKA1 overexpression reverses the promoting effect of LINC00963 on cisplatin resistance of ESCC. LINC00963 regulates TE-1/DDP cells bioactivity and mediates cisplatin resistance through interacting with miR-10a and upregulating SKA1 expression.

Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Decreased risk of radiation pneumonitis with concurrent use of renin-angiotensin system inhibitors in thoracic radiation therapy of lung cancer.

Background: Radiation pneumonitis (RP) is the primary dose-limiting toxicity associated with radiotherapy. This study aimed to observe the effects of renin-angiotensin system inhibitors in Chinese patients with lung cancer who received thoracic radiation. Methods: Patients with lung cancer who received thoracic radiation at a total dose of ≥45 Gray between October 2017 and December 2022 were enrolled in this study. We retrospectively evaluated the factors influencing grade 2 or higher RP. Results: A total of 320 patients were enrolled in this study; 62 patients were identified as angiotensin receptor blockers or angiotensin-converting enzyme inhibitor users. Additionally, 99 patients (30.9%) had grade 2 or higher RP, and the incidence in the renin-angiotensin system inhibitor group was 17.7% (11 out of 62 patients). Patients in the renin-angiotensin system inhibitors (RASi) group were older and had a higher percentage of males, lower percentage of ECOG score 0, higher percentage of hypertension, and higher percentage of adenocarcinoma than those in the non-RASi group. ECOG score [hazard ratio (HR) = 1.69, p = 0.009], history of smoking (HR = 1.76, p = 0.049), mean dose (HR = 3.63, p = 0.01), and RASi (HR = 0.3, p = 0.003) were independent predictive factors for RP. All subgroups benefited from RASi. Conclusion: This study showed that oral RASi administration has the potential to mitigate the incidence of grade 2 or higher RP in patients with lung cancer undergoing thoracic radiotherapy. To validate and further substantiate these findings, additional prospective research is warranted.

Intracavitary cardiac metastasis of cervical squamous cell carcinoma with immune thrombocytopenia: a rare case report.

Cervical cancer is a prevalent gynecological malignancy; however, intracavitary cardiac metastasis of cervical squamous cell carcinoma is exceptionally rare. In addition, the co-occurrence of cervical cancer and right ventricular cancer thrombus with autoimmune diseases is extremely uncommon. Furthermore, the role of immune checkpoint inhibitors in the treatment process of such cases remains controversial. Given the scarcity of reported cases, it is imperative to document and highlight this unique presentation, providing novel insights into diagnosis and management strategies. We present the case of an adult patient diagnosed with cervical cancer and concurrent right ventricular cancer thrombus, accompanied by immune thrombocytopenia (ITP). The patient exhibited resistance to conventional ITP drugs, with suboptimal platelet response. However, upon achieving initial control of the tumor, the patient's platelet counts returned to normal. Notably, the addition of immune checkpoint inhibitors targeting PD-L1 resulted in effective tumor control, accompanied by sustained high platelet levels. Unfortunately, during subsequent anti-tumor therapy, the patient experienced a prolonged platelet rise time, rendering continuous effective anti-tumor therapy and anticoagulant therapy unattainable. This led to a gradual increase in intraventricular thrombosis, ultimately resulting in the patient's demise due to circulatory failure. This rare case sheds light on the potential alleviation of ITP in patients with tumor complications through effective antitumor therapy. The successful control of ITP after tumor management highlights the importance of integrated treatment approaches. Furthermore, the inclusion of immune checkpoint inhibitors demonstrated their potential role in achieving tumor control and maintaining platelet levels. However, the prolonged platelet rise time observed during subsequent therapy underscores the challenges in maintaining both effective anti-tumor therapy and anticoagulant therapy, necessitating careful management strategies. This case report emphasizes the need for a comprehensive evaluation and tailored therapeutic interventions in similar complex scenarios. In summary, this case report offers valuable clinical insights into the management of intracavitary cardiac metastasis of cervical squamous cell carcinoma, the coexistence of immune thrombocytopenia, and the potential implications of immune checkpoint inhibitors in such cases. Understanding these rare occurrences and their clinical impact can contribute to improved diagnostic approaches, therapeutic decision-making, and patient outcomes.

Pathologic response to neoadjuvant chemotherapy in ovarian cancer and its association with outcome: A surrogate marker of survival.

OBJECTIVE: We aimed to validate whether pathologic response (pR) to neoadjuvant chemotherapy (NACT) using a three-tier chemotherapy response score (CRS) is associated with clinical outcome in ovarian cancer (OC) and could be used as surrogate marker for survival. METHODS: We conducted a retrospective study of OC patients with FIGO stage III/IV disease who received NACT and graded response as no or minimal (CRS 1), partial (CRS 2), or complete/near-complete (CRS 3) pR using tissue specimens obtained from omentum. Uni- and multivariate survival analyses were performed accounting for age, FIGO stage, debulking and BRCA status as well as neoadjuvant use of bevacizumab. RESULTS: CRSs 1, 2 and 3 were found in 41(31%), 62 (47%) and 30 (22%) of the 133 examined cases. Response to NACT was associated with significantly improved progression-free (PFS, p < 0.001) and overall survival (OS, p = 0.011). Complete/ near-complete pathologic response (CRS3) was associated with improved PFS (median 24.8 vs. 12.5 months, unadjusted HR 0.28 [95%CI 0.15-0.54], p < 0.001; adjusted hazard ration (aHR) 0.31 [95% CI 0.14-0.72], p = 0.007) and OS (median 63.3 vs. 32.1 months, unadjusted HR 0.27 [95%CI 0.10-0.68], p = 0.006; aHR 0.32 [95% CI 0.09-1.11], p = 0.072) when compared to no or minimal response (CRS1). CONCLUSIONS: We validate a three-tier CRS for assessment of pathologic response to NACT in OC and demonstrate its prognostic independence of BRCA status or neoadjuvant bevacizumab use. Improving pR rates may be a useful goal of NACT in OC with the expectation of improved survival. The CRS may be a useful endpoint in clinical trials in OC.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Clinical outcomes of clip-assisted endoscopic cyanoacrylate injection versus conventional endoscopic cyanoacrylate injection in treating gastric varices with a gastrorenal shunt.

BACKGROUND AND STUDY AIMS: The optimal treatment for gastric varices (GVs) is a topic that remains definite for this study. This study compared the clinical outcomes of clip-assisted endoscopic cyanoacrylate injection (clip-ECI) to conventional endoscopic cyanoacrylate injection (con-ECI) for the treatment of GVs with a gastrorenal shunt. PATIENTS AND METHODS: Data were collected retrospectively in five medical centers from 2015 to 2020. The patients were treated with con-ECI (n = 126) or clip-ECI (n = 148). Clinical characteristics and procedural outcomes were compared. Patients were followed until death, liver transplantation or 6 months after the treatment. The primary outcome was rebleeding, and the secondary outcome was survival. RESULTS: There were no significant differences in age, sex, etiology, shunt diameter and Child-Pugh classification between the two groups. Fewer GVs obliteration sessions were required in the clip-ECI group than in the con-ECI group (p = 0.015). The cumulative 6-month rebleeding-free rates were 88.6% in the clip-ECI group and 73.7% in the con-ECI group (p = 0.002). The cumulative 6-month survival rates were 97.1% in the clip-ECI group and 94.8% in the con-ECI group (p = 0.378). CONCLUSIONS: Compared with con-ECI, clip-ECI appears more effective for the treatment of GVs with a gastrorenal shunt, which required less sessions and achieved a higher 6-month rebleeding-free rate.

A retrospective study of audiological outcomes after endoscopic tympanoplasty and tympanomastoidectomy in patients with cholesteatoma.

OBJECTIVES: To investigated whether endoscopic tympanoplasty and tympanomastoidectomy could present satisfying audiological outcomes for cholesteatoma patients. METHODS: This was a retrospective study of 83 patients with cholesteatoma who underwent endoscopic tympanoplasty and tympanomastoidectomy between 2019 and 2021. The preoperative and postoperative audiological evaluations were performed. The evaluation methods included air conduction (AC), bone conduction (BC), and air-bone gap (ABG) procedures. RESULTS: Eighty-three patients were included in the study, all of whom underwent endoscopic tympanoplasty and tympanomastoidectomy. Forty-seven patients presented postoperative ABG≤20 dB (59.49%). The frequencies tested included low-frequency (LF), middle-frequency (MF), high-frequency (HF), and pure-tone average (PTA). All three audiological parameters significantly decreased after surgery (P < 0.05) at every frequency, except for BC-LF (P > 0.05). There were also significant differences between the preoperative and postoperative proportions of degree of hearing (P < 0.05). Additionally, shifts in AC, BC, and ABG were linearly related to preoperative AC, BC, and ABG. Lastly, postoperative ABG-PTA presented differently depending on preoperative stapes superstructure conditions (present: 15.81 ± 11.23 dB, absent: 22.94 ± 12.20 dB, P = 0.009). CONCLUSIONS: Our study of endoscopic tympanoplasty and tympanomastoidectomy presented complete audiological outcomes for cholesteatoma patients. It had a positive surgery success rate and improved AC, BC, and ABG at every frequency except BC-LF. Additionally, AC-LF and AC-MF improved to a greater degree than AC-HF due to these procedures. Moreover, the linear regression analyses demonstrated that preoperative ABG-PTA was the most efficient audiological indicator for surgery. Likewise, the preoperative condition of the stapes superstructure was proved to be the most efficient anatomical indicator for hearing outcomes.

Screening of pesticides in serum, urine and cerebrospinal fluid collected from an urban population in China.

Human exposure to pesticides is a topic of public health concern for decades. Pesticide exposures have been assessed through the analysis of urine or blood matrices, but little is known on the accumulation of these chemicals in cerebrospinal fluid (CSF). CSF plays an important role in maintaining physical and chemical balance of the brain and central nervous system and any perturbation can have adverse effects on health. In this study, we investigated the occurrence of 222 pesticides in CSF from 91 individuals using gas chromatography-tandem mass spectrometry (GC-MS/MS). Measured pesticide concentrations in CSF were compared with those in 100 serum and urine specimens from individuals living in the same urban location. Twenty pesticides were found in CSF, serum and urine, at levels above the limit of detection. Three most frequently detected pesticides in CSF were biphenyl (100%), diphenylamine (75%), and hexachlorobenzene (63%). Median concentrations of biphenyl in CSF, serum and urine were 1.11, 10.6, and 1.10 ng/mL, respectively. Six triazole fungicides were found only in CSF, but not in other matrices. To our knowledge, this is the first study to report pesticide concentrations in CSF in a general urban population.

Hepatocyte-derived exosomes deliver H2AFJ to hepatic stellate cells and promote liver fibrosis via the MAPK/STMN1 axis activation.

Hepatic stellate cells (HSCs) activate and acquire proliferative features in response to liver injury. However, mechanisms involved in the activation of fibrotic HSCs remain uncharacterized. This study aims at elaborating the mechanistic basis by which exosomal H2AFJ derived from hepatocytes might affect the activation of HSCs and liver fibrosis. Bioinformatics analysis based on transcriptomic RNA-seq data was used to screen out the downstream regulatory genes and pathways of H2AFJ. Mouse hepatocytes AML-12 cells were stimulated with CCl4 to mimic an in vitro microenvironment of liver fibrosis, from which exosomes were isolated. Next, HSCs were co-cultured with hepatocyte-derived exosomes followed by detection of HSC migration and invasion in the presence of manipulated H2AFJ and STMN1 expression and MAPK pathway inhibitor. It was found that H2AFJ was highly expressed in hepatocyte-derived exosomes after CCl4 stimulation. Hepatocyte-derived exosomal H2AFJ promoted HSC migration and invasion. H2AFJ upregulated c-jun-mediated STMN1 by activating the MAPK signaling pathway. Furthermore, in vivo experiments verified that silencing of H2AFJ attenuated liver fibrosis in mice, while restoration of STMN1 negated its effect. Collectively, hepatocyte-derived exosomal H2AFJ aggravated liver fibrosis by activating the MAPK/STMN1 signaling pathway. This study provides a potential therapeutic target for alleviating liver fibrosis.

Radiation combined with KRAS-MEK inhibitors enhances anticancer immunity in KRAS-mutated tumor models.

KRAS mutation is a common driver in solid tumors, and KRAS-mutated tumors are relatively resistant to radiotherapy. Therefore, we investigated the combined effect of radiation and KRAS-MEK inhibitors (AMG510 and trametinib) in KRAS-mutated tumors. The expression of programmed death-ligand 1 (PD-L1), major histocompatibility complex (MHC) class I molecules, and cytokines in KRAS-mutated cell lines was assessed using flow cytometry, western blot analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. In vivo, tumor growth, T cell infiltration, and gene sequencing analyses were conducted in 2 murine KRAS-mutated models. Both AMG510 and trametinib decreased the radiation-induced increase in PD-L1 expression. Radiation and trametinib additively induced the expression of CXCL10 and CXCL11 cytokines and MHC class I in murine CT26 and LLC cell lines. The combination of trametinib and radiation controlled tumor growth and induced more infiltration of CD4+ and CD8+ T cells in vivo, wherein tumor inhibition function and the survival period of mice could be reduced by CD8+ and/or CD4+ T cell depletion. The expression levels of immune-related genes also increased in the combination therapy group. Our results indicate that KRAS-MEK inhibitors in combination with radiotherapy can enhance antitumor immunity, providing new therapeutic strategies for KRAS-mutated tumors.

Platycodon grandiflorus polysaccharides deeply participate in the anti-chronic bronchitis effects of platycodon grandiflorus decoction, a representative of "the lung and intestine are related".

Platycodon grandiflorus (Jacq.) A. DC. (PG) root is one of the most commonly used medicine-food materials for respiratory discomfort in Asia, usually in the form of a decoction or leaching solution. As everyone knows, both of decoction and leaching solution is a polyphase dispersion system, containing low-molecular-weight water-soluble active ingredients and hydrophilic macromolecules. This study aimed to discuss the synergistic effect of Platycodon grandiflorus polysaccharide (PGP) and platycodin D (PD) in PG decoction against chronic bronchitis (CB) and the mechanism underlying. A series of PGP, PD, and PGD + PD suspensions were administrated to CB model rats, on the levels of whole animal and in situ intestinal segment with or without mesenteric lymphatic vessels ligation. It exhibited that PGP exhibited synergistic effects with PD, on improving the histopathological abnormity, mucus secretion excess, and immunological imbalance in lung of CB model rat, closely associated with its modulations on the mucosal immunity status in small intestine. The polysaccharide macromolecules in PG decoction or leaching solution should be responsible for the modulation of pulmonary immune state, possibly through the common mucosal immune between small intestine and lung. These results might be a new perspective that illustrates the classical theory of "the lung and intestine are related" in traditional Chinese medicine.

Sensorineural damage in chronic suppurative otitis media with and without cholesteatoma: a comparative study.

Background: Chronic suppurative otitis media (CSOM) is a common otolaryngology disease, and cholesteatoma is the most aggressive type of CSOM. CSOM with and without cholesteatoma both result in a certain level of sensorineural damage, which can be categorized as air conduction (AC), bone conduction (BC), or air-bone gap (ABG), and AC, BC, and ABG are affected by many factors. Further analyses and comparisons of factors affecting sensorineural damage in CSOM with and without cholesteatoma were conducted in this study. Methods: A comparative study was conducted of 79 patients with CSOM (39 with cholesteatoma and 40 without cholesteatoma) whose diagnoses were mainly based on chronic middle ear infections and hearing loss (HL), typical computed tomography (CT) and surgical findings. Audiological evaluation included AC, BC and ABG, and sensorineural damage was defined as mixed and sensorineural HL (SNHL). Results: In relation to the types of HL, there were no significant differences between both groups. The CSOM with cholesteatoma group had significantly greater AC (P=0.000) and a significantly greater ABG (P>0.05) than the CSOM without cholesteatoma group, but BC did not differ significantly between both groups (P>0.05). The average AC-middle frequency (MF), AC-high frequency (HF), ABG-MF and ABG-HF of CSOM without cholesteatoma were smaller than these of CSOM with cholesteatoma (P<0.05). The degree of HL differed significantly between both groups (P=0.000). The CSOM with cholesteatoma group showed a higher level of HL than the CSOM without cholesteatoma group. The presence of cholesteatoma was presented a protective factor associated with sensorineural damage (P<0.05), while higher degrees of hearing and aging were risk factors (P<0.05), respectively. Conclusions: Our direct comparisons showed that HL progressed more rapidly in the CSOM with cholesteatoma group, which had higher frequencies in relation to AC, the ABG, and severity. However, in relation to BC, there were no significant differences between both groups, which was in line with the similar proportions of the types of HL in both groups. The logistic regression showed that the presence of cholesteatoma was a protective factor, and the degree of hearing and aging were risk factors associated with sensorineural damage.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies that seriously threaten people's health worldwide. DEAD-box helicase 51 (DDX51) is a member of the DEAD-box (DDX) RNA helicase family, and drives or inhibits tumor progression in multiple cancer types. AIM: To determine whether DDX51 affects the biological behavior of ESCC. METHODS: The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry (IHC) analyses and quantitative PCR (qPCR). We knocked down DDX51 in ESCC cell lines by using a small interfering RNA (siRNA) transfection. The proliferation, apoptosis, and mobility of DDX51 siRNA-transfected cells were detected. The effect of DDX51 on the phosphoinositide 3-kinase (PI3K)/AKT pathway was investigated by western blot analysis. A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth. RESULTS: DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC. Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis. Moreover, DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates. Investigations into the underlying mechanisms suggested that DDX51 knockdown induced inactivation of the PI3K/AKT pathway, including decreased phosphorylation levels of phosphate and tensin homolog, PI3K, AKT, and mammalian target of rapamycin. Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development. Finally, we injected DDX51 siRNA-transfected TE-1 cells into an animal model, which resulted in slower tumor growth. CONCLUSION: Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway; thus, DDX51 might be a therapeutic target for ESCC.

Comprehensive Analysis of Acetylation-Related lncRNAs and Identified AC099850.3 as Prognostic Biomarker in Non-Small Cell Lung Cancer.

The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients.

Effect of Very Advanced Maternal Age on Pregnant Women and Fetuses.

OBJECTIVE: To compare the difference in the effect on pregnant women and fetuses between very advanced maternal age (age of or over 45 years) and other ages (age below 45 years). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Changyi People's Hospital, China, from June 2017 and September 2020. METHODOLOGY: Four-hundred singleton pregnancies were selected. One hundred and three pregnant women at age of or over 45 years (Group A) and 297 pregnant women at age below 45 years (Group B) were grouped by age. Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), incidence of pregnancy complications and fetal outcomes were compared. RESULT: Group A had higher TC and HDL-C than Group B at 12-week, 32-week pregnancy and 3 days after delivery (all p <0.001); Group A had higher TG than Group B at 12-week, 32-week pregnancy and 3 days after delivery (p=0.003, p <0.001 and p <0.001), respectively. Group A had higher incidence of gestational diabetes mellitus (GDM), pregnancy complicated with leiomyoma, gestational hypertension, placenta previa, placental abruption, anemia and postpartum hemorrhage than Group B (all p <0.001). Group A had higher incidence of fetal distress and preterm birth than Group B (both p <0.001). The difference in fetal weight and Apgar score of 5-min infants compared between the two groups was significant (both p<0.001). CONCLUSION: The incidence of gestational complications and adverse perinatal outcomes may be increased in very advanced maternal age singleton pregnant women aged over 45 years. Key Words: Very advanced maternal age, Pregnant women, Pregnancy, Fetus, Complications.

Optimization of Enzyme-Assisted Extraction and Purification of Flavonoids from Pinus koraiensis Nut-Coated Film and Antioxidant Activity Evaluation.

Pinus koraiensis nut-coated film is a kind of by-product of nut processing, which has been shown to contain flavonoids, polyphenols, and other substances that can be used to produce natural antioxidant extracts. In this study, response surface methodology (RSM) was used to optimize the extraction process of flavonoids of P. koraiensis nut-coated film (PNF), and macroporous resin HPD600 was used to purify PNF (P-PNF). Its antioxidant activity was examined by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging capacity, oxygen free radical absorption capacity (ORAC), total oxygen radical capture (TRAP), and iron ion reduction capacity. Under the ideal extraction conditions comprising a cellulase dosage of 90 U/g, a material/liquid ratio of 1:20 (g/mL), and an extraction time of 2 h, the PNF yield was 3.37%. Purification conditions were sample concentration of 2.0 mg/mL, pH of 5, water washing volume of 3 bed volume (BV), eluent ethanol concentration of 50%, and volume of 2 BV. The P-PNF recovery was 84.32%, and purity increased from 33.80% to 61.70%. Additionally, P-PNF showed increased antioxidant activity compared to PNF. Cumulatively, this study obtained the optimal values for the process parameters in order to achieve the maximum rates of extraction of PNF for economically optimal production at an industrial scale.