With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

Objective To study the effect and mechanism of estradiol (E

BACKGROUND: Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology. OBJECTIVE: We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study. SEARCH STRATEGY: We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM." INCLUSION CRITERIA: We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment. DATA EXTRACTION AND ANALYSIS: The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms. RESULTS: The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection. CONCLUSION There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.
Adult ; Child ; China ; Combined Modality Therapy ; Complementary Therapies ; Data Mining ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional/methods* ; Observational Studies as Topic ; Randomized Controlled Trials as Topic ; Young Adult

Objective:To analyze the clinical characteristics and short-term prognosis of patients with acute asthmatic attack and comorbid bronchiectasis.Methods:The data of patients hospitalized for acute asthmatic attack in the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 1, 2012 to December 31, 2021 were retrospectively collected and analyzed. According to whether or not co-existing with bronchiectasis, all the patients were divided into asthmatic with bronchiectasis group and asthmatic without bronchiectasis group. Then the general conditions, comorbidities, pulmonary function test, grades of asthma severity, laboratory examination and in-hospital short-term prognosis of two groups were analyzed.Results:A total of 580 hospitalized patients with acute asthma attack were included, of which 132 cases (22.76%) were classified into asthmatic with bronchiectasis group and 448 cases (77.24%) were classified into asthmatic without bronchiectasis group. Co-existing with obsolete pulmonary tuberculosis and anxiety/depression in asthmatic with bronchiectasis group were more common than that in asthmatic without bronchiectasis group (13.64% vs 5.36%; 7.58% vs 2.68%) (both P<0.05). The pre-bronchodilator forced vital capacity (FVC) and its percentage to the predicted value (FVC%pred), forced expiratory volume in 1 second (FEV 1) and its percentage to the predicted value (FEV 1%pred), FEV 1/FVC and post-bronchodilator FEV 1 in asthmatic with bronchiectasis group were lower than those in the asthmatic without bronchiectasis group [2.44 (1.90, 3.01) vs 2.69 (2.10, 3.68) L, 1.55 (1.13, 2.00) vs 1.78 (1.25, 2.52) L, 70.14% (67.39%, 85.92%) vs 79.63% (70.00%, 89.52%), 70.00% (54.38%, 78.11%) vs 70.00% (61.47%, 85.00%), 61.57% (56.29%, 73.03%) vs 66.67% (60.00%, 75.00%), 1.72 (1.21, 2.18) vs 1.89 (1.37, 2.55) L] (all P<0.05). In previous year, the proportion of patients receiving hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group was higher than that in asthmatic without bronchiectasis group (15.15% vs 8.93%) ( P<0.05). The peak months of hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group were April, July and October, and the peak months in asthmatic without bronchiectasis group were April and September. The length of hospital stay was longer and the proportion of patients receiving invasive ventilation was higher in asthmatic with bronchiectasis group than those in asthmatic without bronchiectasis group [10.06 (7.62, 13.94) vs 9.95 (7.15, 13.76) d; 5.30% vs 2.01%] (both P<0.05). The risk factors for invasive mechanical ventilation in asthmatic patients with acute attack during hospitalization were co-existing with bronchiectasis, smoking, high level of partial pressure of carbon dioxide in arterial blood, serum creatinine and creatine kinase. Conclusion:Asthma patients with comorbid bronchiectasis have more frequent acute attack, a longer hospitalization due to acute asthmatic attack and a higher probability of invasive ventilation during hospitalization.

Objective: Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south China. In this study, we aimed to explore its bioactive constituent which contributes to the anti-inflammatory activity. Methods: Polyphenol-enriched and polyphenol-deprived fractions (PRF and PDF, respectively) were separated from the ethanolic extract by HPD300 macroporous resin-based method, and their anti-inflammatory activities were investigated on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats. The possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 cells. Results: Both Folin-Ciocalteu and

Parkinson disease (PD) is the second-most common neurodegenerative disorder. Its main pathological mechanism is the selective degeneration and deletion of dopaminergic neurons in the dense part of the substantia nigra and the damage of dopaminergic neurons caused by the abnormal deposition of a Lewy body, leading to a decreased dopamine level. Positron emission computed tomography (PET)/single photon emission computed tomography (SPECT) is a molecular imaging technology that can directly or indirectly reflect changes in molecular levels by using a specific tracer. With the research and development on the tracers of related enzymes for labeling dopamine transporter and dopamine receptor and for being involved in dopamine formation, this imaging technology has been applied to all aspects of PD research. It not only contributes to clinical work but also provides an important theoretical basis for exploring the pathological mechanism of PD at a molecular level. Therefore, this review discusses the application value of PET/SPECT in PD in terms of early diagnosis, disease severity evaluation, clinical manifestations, differential diagnosis, and pathological mechanism.

Objective To investigate the expression differences and significance of periostin (PN) in eyelid basal cell carcinoma associated fibroblasts (BCAFs) andnormal fibroblasts (NFs) after separation,culture,purification and identification.Methods The third generation of purified BCAFs and NFs was selected,and the concentrations of cell suspensions were modulated to 20 × 106 L-1 by trypsin,and then the cell suspension were seeded and cultured in 6-well plate by 2 mL per well.The cell culture supernatants were collected when BCAFs and NFs were cultured by serum-free medium for 48 h,then the content of PN in cell culture supernatants from BCAFs and NFs was detected by enzyme-linked immunosorbent assay (ELISA).The glass coverslips were placed at the bottom of the 6-well plate to make cell slides,and then the expression of PN in BCAFs and NFs cells were tested by immunofluorescence staining.Results ELISA showed that the content of PN in cell culture supernatants from BCAFs and NFs was (9.26 ± 2.35) μg · L-1 and (2.57 ± 0.41) μg · L-1.And the expression level of PN in BCAFs tested by immunofluorescence staining technology was higher than that in NFs cells,and the differences were statistically significant (all P ＜ 0.05).Conclusion The expression and secretion of PN in the eyelid BCAFs were highly enhanced when compared with NFs,suggesting that periostein may promote or inhibit the occurrence and development of the eyelid basal cell carcinoma in the microenvironment of the eyelid basal cell carcinoma.

OBJECTIVETo observe the effect of Schistosoma japonicum cysteine protease inhibitor (rSjCystatin) for treatment of lipopolysaccharide (LPS)-induced sepsis in mice.

METHODSAfter a week of adaptive feeding, 54 BALB/c mice were randomly divided into normal control group (group A), sepsis group (group B), and rSjCystatin intervention group (group C). The mice in group A received an intraperitoneal injection of PBS (100 µL), and those in groups B and C were injected with PBS (100 µL) containing LPS (10 mg/kg); the mice in group C were also intraperitoneally injected with 25 µg sjCystatin in 100 µL PBS 30 min after LPS injection. From each group, 10 mice were randomly selected 24 h after PBS or LPS injection for detecting serum levels of TNF-α, IL-6, and IL-10 using ELISA and the levels of ALT, AST, BUN, and Cr using automatic biochemical analyzer; the pathological changes in the liver, lung and kidney were observed with HE staining. The remaining 8 mice in each group were used for observing the changes in the general condition and the 72-h survival.

RESULTSThe 72-h survival rates of the mice was 100% in group A, 0 in group B, and 36% in group C, showing a significant difference among the 3 groups (P<0.05). Compared with those in group A, the mice in group B exhibited obvious liver, lung, and renal pathologies with increased levels of ALT, AST, BUN, Cr, IL-6, and TNF-α (P<0.05). Treatment with sjCystatin significantly lessened LPS-induced organ pathologies, lowered the levels of liver and renal functional indexes and the pro-inflammatory cytokines, and increased the serum level of IL-10 in the mice (P<0.05).

CONCLUSIONSjCystatin can produce a significant therapeutic effect on sepsis induced by LPS in mice.

Objective To evaluate the feasibility and safety of cap-assisted endoscopic nylon loop ligation (C-ENLL) as a new and simple method on gastric fundus submucosal tumors. Methods 74 cases with small gastric fundus submucosal tumors ≤2.00 cm in diameter were reviewed between January 2015 and June 2016. All cases were treated by C-ENLL. The clinical efficacy was analyzed. Results All the 74 patients underwent endoscopic ultrasonography before operation, 70 cases originated from the muscularis propria, 3 cases originated from the muscularis mucosae, 1 case originated from the submucosa. The average diameter of the lesions ranged 0.50 ～ 1.80 cm. C-ENLL achieved an en bloc resection rate of 100.0％, with a mean total procedure time of 26 min. Two patients developed delayed perforation, were treated with nylon rope and metal clip purse suture wound. All of whom were managed successfully. There was no delayed bleeding after operation. Pathological examination showed that 66.2％ (49/74) of the tumors were gastrointestinal stromal tumors. No tumor recurrence was observed during the follow-up. Conclusion The C-ENLL may be a feasible and safe method for the treatment of small gastric fundus submucosal tumors.

OBJECTIVETo establish a method for isolation, cryopreservation and recovery of the highly viable human peripheral blood monomuclear cells (PBMNCs) so as to achieve the long-term preservation of PBMNCs.

METHODSA total of 80-100 ml peripheral blood were collected from the healthy volumteers aged over 50 years old. The PBMNCs were isolated by the Ficoll density gradient technique and cryopreserved gradually by program control method in liquid nitrogen freezer of -196 °C. The serum-free medium and autoloqous plasma medium were test for preservation of PBMNCs. The cell viability was assessed at time point of 1, 2, 4, 8, 12 and 24 months after thawing. Finally, the proliferation ability, purity and cytotoxicity were compared between the autologous immune lymphocytes (AIL) induced from cryopreserved PBMNCs and AIL as control from fresh PBMNCs.

RESULTSAfter separating, the cell viability was 99.6%±0.4%, and the recovery rate of lymphocytes was 58.4%±6.52%. The cell recovery rate of lymphocyte was 89.7%±3.82% at 24 months. The quality assurance program was reliable within 2 years of running. The AIL cells induced with cryopreserved PBMNCs were not significantly different from those induced from fresh PBMNCs in terms of proliferative action, purity and cytotoxicity(CD3(+)CD8(+) ≥45%,CD3(+)CD56(+) NKT≥10%,CD4(+)CD25(+) NKT≤10%).

CONCLUSIONManual separation of lymphocytes in vitro can get enough high-quality PBMNCs. The long-term cryopreserved PBMNC still maintain their high viability. The reinfusion of the clinical autologous immune cells would be advantageous for early tumor immunotherapy. Human AIL induced from cryopreserved PBMNC maintain their anti-tumor ability. These findings have the important implications for the application of these cells to adoptive cellular therapy.