Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM.@*METHODS@#Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue.@*RESULTS@#In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05).@*CONCLUSION@#EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

Advances in the periodontal surgical flaps techniques to preserve gingival papilla / 中华口腔医学杂志

Papilla preservation in periodontal surgery is not only beneficial to maintain postoperative aesthetics and good oral hygiene but also contributes to obtaining good periodontal regeneration outcomes. Various periodontal flaps have been designed to preserve the gingival papilla, which constitutes the clinical basis for periodontal open flap debridement and periodontal regeneration surgery. A comprehensive understanding of their design purpose, indications, and technical key points will help clinicians to choose the optimal surgical plan, and thus improve the clinician's treatment levels, and obtain good clinical outcomes. Therefore, this article aims to introduce the design background, indications, and technical key points of various surgical flaps, such as papilla preservation technique, modified papilla preservation technique, simplified papilla preservation flap, etc.

Research progress and application prospect of stem cells in inflamed dental tissues on periodontal bone regeneration / 中华口腔医学杂志

Tissue engineering has become a research hotspot regarding periodontal bone regeneration in recent years. Generally, stem cells used in periodontal tissue engineering are derived from healthy dental tissues, while restricted due to the strict indication of tooth extraction and limited sources. Stem cells in inflamed dental tissues mainly derive from inflamed pulp, periapical and periodontal tissues. Stem cells in inflamed dental tissues are abundant and retain most of the basic characteristics of stem cell compared with the ones derived from healthy dental tissues, which can be a promising source of stem cells for periodontal bone regeneration. In this review, we summarize the current application and prospect of stem cells in inflamed dental tissues on periodontal bone regeneration, and then discuss their feasibility as seed cells, in order to provide a reference for future research and clinical application of stem cells in inflamed dental tissues.

Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis.@*METHODS@#The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed.@*RESULTS@#The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L.@*CONCLUSION@#High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL).@*METHODS@#A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored.@*RESULTS@#Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05).@*CONCLUSIONS@#The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Abstract Objective To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design A retrospective single-institution cohort study. Patients The perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors' institution between November 2012 and June 2019 were retrospectively analyzed. Methods The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations The number of enrolled patients was relatively small and patients' treatment options varied. Conclusions A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target.

Effect of 577nm micropulse laser on chronic central serous chorioretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy and safety of 577nm subthreshold micropulse laser(SML)in patients with chronic central serous chorioretinopathy(CSC).METHODS: Prospective single-arm case study. There were 24 patients(32 eyes)with chronic CSC treated by using 577nm SML. A total of 6mo was followed up after treatment, the best corrected visual acuity(BCVA, LogMAR)and optic coherence tomography(OCT)were performed at each month. Fluorescein fundus angiography(FFA)was performed at 1,3 and 6mo after treatment.RESULTS: The BCVA was 0.46±0.34 and central retinal thickness(CRT)was 259.15±57.54μm of 32 eyes at baseline period. After treatment of SML at 1mo, there was no subretinal fluid in 21 eyes(66%), and subretinal fluid was observed in 11 eyes(34%). The BCVA was 0.43±0.27, the CRT was 232.13±42.58μm. CRT was significantly reduced compared to the baseline period(P&#x003C;0.05). After treatment of SML at 3mo, subretinal fluid and fluorescein leakage from retinal pigment epithelium(RPE)were observed in 5 eyes(16%). The BCVA was 0.39±0.26 and CRT was 231.26±49.25μm. The CRT was still significantly lower than baseline period(P&#x003C;0.05). The 5 eyes with subretinal fluid and leaked fluorescein were treated by using SML again. After treatment at 6mo, subretinal fluid was observed in only 3 eyes(9%). The BCVA was 0.19±0.47 and CRT was 217.25±35.54μm. Both of the BCVA and CRT showed a significant improvement from the baseline period(P&#x003C;0.05). CONCLUSION:SML seems effective and safe for treatment of chronic CSC. It may be an alternative way for treatment of chronic CSC.

Effects of Interactive Dynamic Scalp Acupuncture on Motor Function and Gait of Lower Limbs after Stroke: A Multicenter, Randomized, Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on motor function and gait of the lower limbs in post-stroke hemiplegia patients.@*METHODS@#A total of 231 patients with post-stroke hemiplegia was randomly divided into IDSA (78 cases), SCT (78 cases), and TSA (75 cases) groups by a random number table. Scalp acupuncture (SA) and lower-limb robot training (LLRT) were both performed in the IDSA and SCT groups. The patients in the TSA group underwent SA and did not receive LLRT. The treatment was administered once daily and 6 times weekly for 8 continuous weeks, each session lasted for 30 min. The primary outcome measures included Fugl-Meyer assessment of the lower extremity (FMA-LE), berg balance scale (BBS), modified barthel index (MBI), and 6-min walking test (6MWT). The secondary outcome measures included stride frequency (SF), stride length (SL), stride width (SW), affected side foot angle (ASFA), passive range of motion (PROM) of the affected hip (PROM-H), knee (PROM-K) and ankle (PROM-A) joints. The patients were evaluated before treatment, at 1- and 2-month treatment, and 1-, and 2-month follow-up visits, respectively. Adverse events during 2-month treatment were observed.@*RESULTS@#Nineteen patients withdrew from the trial, with 8 in the IDSA and 5 in the SCT groups, 6 in the TSA group. The FMA-LE, BBS, 6MWT and MBI scores in the IDSA group were significantly increased after 8-week treatment and 2 follow-up visits compared with the SCT and TSA groups (P<0.05 or P<0.01). Compared with pre-treatment, the grade distribution of BBS and MBI scores in the 3 groups were significantly improved at 1, 2-month treatment and 2 follow-up visits (P<0.05 or P<0.01). The SF, PROM-H, PROM-K and PROM-A in the IDSA group was significantly increased compared with the SCT and TSA groups after 8-week of treatment (P<0.05 or P<0.01). Compared with the SCT group, ASFA of the IDSA group was significantly reduced after 8-week of treatment (P<0.05). SF, SL, PROM-K and PROM-A were significantly increased at the 2nd follow-up visit whereas the ASFA was significantly reduced in the IDSA group compared with the SCT groups at 1st follow-up visit (P<0.05 or P<0.01). The SF was significantly increased in the SCT group compared with the TSA group after 8-week treatment (P<0.05). Compared with the TSA group, PROM-K, PROM-A were significantly increased at the 2nd follow-up visit (P<0.05).@*CONCLUSIONS@#The effects of IDSA on lower-limb motor function and walking ability of post-stroke patients were superior to SCT and TSA. The SCT was comparable to TSA treatment, and appeared to be superior in improving the motion range of the lower extremities. (Registration No. ChiCTR1900027206).

Influence of hemoglobin level(Hb) on survival and prognosis of elderly hip fracture at admission / 中国骨伤

OBJECTIVE@#To analyze the relationship between hemoglobin(Hb) level on admission and survival prognosis of patients with hip fracture.@*METHODS@#From February 2016 to October 2018, 249 elderly patients with hip fracture were surgically treated including 62 males and 187 females;the age ranged from 60 to 91(73.67±10.52) years;the time from injury to operation was (6.79±2.27) d. The clinical and laboratory examination results were collected. The Hb level at admission and the mortality at 30, 90, 180 and 360 days after operation were observed. According to the Hb level at admission, the patients were divided into Hb<120 g/L and Hb≥120 g/L groups. The survival conditions of the two groups at 30, 90, 180 and 360 days after operation were compared and analyzed. Logistic regression was used to analyze the effect of Hb level on death 30, 90, 180 and 360 days after operation.@*RESULTS@#The mortality rates at 30, 90, 180 and 360 days after operation were 5.22%, 9.24%, 16.87% and 20.48% respectively. The level of Hb at admission was a risk factor for prognosis and death 30, 90, 180 and 360 days after operation(P<0.05). The OR(95% CI) were 2.431(1.475-4.006), 2.625(1.468-4.695), 2.276(1.320-3.925) and 2.082(1.221-3.551) respectively.@*CONCLUSION@#The level of Hb at admission can affect the survival and prognosis of elderly patients with hip fracture. We should further study how to manage the level of Hb before operation.

DNA barcoding of Gentiana crassicaulis in Lijiang and evaluation of root processing methods / 药学学报

The key factors for producing the best quality Chinese herbal medicines are high-quality germplasm, suitable cultivation area and the proper processing methods for herbal raw materials. Gentiana crassicaulis in Gentiana (Sect. Cruciata), Gentianaceae is one of the original plants of the Chinese herb Qinjiao (Gentianae Macrophyllae Radix), and its type specimen was collected in Lijiang, Yunnan. There is a long planting history of the herb in this area. In this study a sampling plot was designated in these traditional planting areas. G. crassicaulis was planted and herbal raw materials were harvested from the plot. The raw materials were prepared locally and at a pharmaceutical factory in Shanghai using processing methods such as "sweating" or "no sweating", "slicing" or "no slicing" (whole root), and "stoving" or "no stoving" (air drying). The quality of all processed samples was evaluated. In addition, molecular markers were determined for identifying cultivated and wild samples from Lijiang, Yunnan. The results are as follows: ① Samples from the sampling plot and the field are taxonomically identified as Gentiana crassicaulis. ② A total of 270 sequences of trnC-GCA-petN, atpB-rbcL, psbN, ndhB-rps7 and ycf1 were obtained, and three genotypes were determined from the cultivated samples; the type III was shared by both cultivated and wild plants. Based on the molecular markers, a DNA barcoding method to identify cultivated and wild samples of G. crassicaulis from Lijiang, Yunnan was established. ③ Total content of loganic acid and gentiopicroside in all samples was ≥ 2.5%, and above the Chinese Pharmacopoeia (2020) limit. ④ In HPLC fingerprinting, 9 common peaks were assigned and similarity between all samples was > 0.999; and ⑤ In a PCA score plot all slice samples were clustered, while whole root samples were scattered. Therefore, our studies could provide basic data for optimizing the processing method, producing best quality Gentianae Macrophyllae Radix, and evaluating the quality of different ecotype varieties and the multiple origin of herbal medicines.

Effect of Interactive Dynamic Scalp Acupuncture on Post-Stroke Cognitive Function, Depression, and Anxiety: A Multicenter, Randomized, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To compare the clinical effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on cognitive function, depression and anxiety in patients with post-stroke cognitive impairment.@*METHODS@#A total of 660 patients with post-stroke cognitive impairment who were admitted to 3 hospitals in Shenzhen City between May 2017 and May 2020 were recruited and randomly assigned to the IDSA (218 cases), SCT (222 cases) and TSA groups (220 cases) according to a random number table. All the patients received conventional drug therapy for cerebral stroke and exercise rehabilitation training. Scalp acupuncture and computer-based cognitive training (CBCT) were performed simultaneously in the IDSA group, but separately in the morning and in the afternoon in the SCT group. The patients in the TSA group underwent scalp acupuncture only. The course of treatment was 8 weeks. Before treatment (M0), 1 (M1) and 2 months (M2) after treatment, as well as follow-up at 1 (M3) and 2 months (M4), the cognitive function of patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) Scales; depression, anxiety, sleep quality, and self-care ability of patients were assessed using Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), and Modified Barthel Index (MBI), respectively. During this trial, all adverse events (AEs) were accurately recorded.@*RESULTS@#There were no significant differences in the MMSE, MoCA, HAMD, HAMA, PSQI, and MBI scores among the 3 groups at M0 (all P>0.05). In the IDSA group, the MMSE, MoCA and MBI scores from M2 to M4 were significantly higher than those in the SCT and TSA groups, while the HAMD, HAMA and PSQI scores were significantly reduced (all P<0.01). The changes of all above scores (M2-M0, M4-M0) were significantly superior to those in the SCT and TSA groups (all P<0.01, except M4-M0 of HAMD). At M2, the severity of MMSE, HAMD, HAMA, PSQI and MBI in the IDSA group was significantly lower than that in the SCT and TSA groups (all P<0.01). There was no serious AE during this trial.@*CONCLUSIONS@#IDSA can not only significantly improve cognitive function, but also reduce depression, anxiety, which finally improves the patient's self-care ability. The effect of IDSA was significantly better than SCT and TSA. (Trial registration No. ChiCTR1900027206).

Mutational spectrum and its prognostic significance in childhood acute lymphoblastic leukemia based on next-generation sequencing technology / 中华血液学杂志

Objective: This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia (ALL) . Methods: Targeted exome by next-generation sequencing (NGS) technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019. Correlation of genetic features and clinical features and outcomes was analyzed. Results: Among the 141 pediatric patients with ALL, 160 somatic mutations were detected in 83 patients (58.9% ) , including 37 grade Ⅰ mutations and 123 grade Ⅱ mutations. Single nucleotide variation was the most common type of mutation. KRAS was the most common mutant gene (12.5% ) , followed by NOTCH1 (11.9% ) , and NRAS (10.6% ) . RAS pathway (KRAS, FLT3, PTPN11) , PAX5 and TP53 mutations were only detected, and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found, and NOTCH1 mutation was mainly detected in T-ALL. The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL (4.16±1.33 vs 2.04±0.92, P=0.004) . The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation. There were no statistically significant differences in sex, age, newly diagnosed white blood cell count, minimal or measurable residual disease monitoring results, expected 3-year event-free survival (EFS) and overall survival (OS) between the two groups (P>0.05) . On the other hand, the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group (P=0.021 and 0.000, respectively) . Among the patients without fusion gene, the EFS of children with grade I mutation was significantly lower than children without grade I mutation (85.5% vs 100.0% , P=0.039) . Among children with B-ALL, the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation (37.5% vs 91.2% , P<0.001) . Conclusion: Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis. Therefore, targeted exome by NGS can be used as an important supplement to the traditional morphology, immunology, cytogenetics, and molecular biology classification.

Celastrol exerts anti-colorectal cancer effect via STAT3 inhibition / 中国药理学通报

Aim To investigate the anti-tumor effect of celastrol(CEL)on colorectal cancer and the possible targets/mechanisms. Methods The cytotoxic activities of CEL were evaluated against A549, HCT-116, HepG2 by CCK-8 method. Western blotting was used to detect the expression level of STAT3 and its upstream and downstream proteins(JAK2, Survivin, MCL-1)in HCT-116 cells before and after CEL treatment Flow cytometry was applied to assess CEL's apoptosis and cell-cycle arrest effect in HCT-116 cells. SPR detection and molecular docking analysis were performed to further assess the binding ability between CEL and STAT3 protein. Lastly, human colorectal cancer organoid culture was constructed to verify the anti-tumor effect of CEL. Results CEL showed significant cytotoxicity to A549(IC50 = 2.37±0.02 μmol·L-1), HCT-116(IC50 = 1.40±0.21 μmol·L-1)and HepG2(IC50 = 2.52±0.02 μmol·L-1). Additionally, CEL could effectively decrease the level of p-STAT3 and the downstream gene expression of STAT3(Survivin and MCL-1)in a concentration-dependent manner; however, CEL did not affect the total level of STAT3 and upstream kinases JAK2. Moreover, CEL could induce apoptosis of HCT-116 cells concentration-dependently and arrest the cell cycle. According to the SPR analysis, CEL showed a strong binding affinity with the KD value(the equilibrium dissociation constant)of 60.38 μmol·L-1. Molecular docking analysis also suggested that CEL bound to the SH2 domain of STAT3. Lastly, CEL showed much better activity than the positive drug oxaliplatin(L-OHP)on all the colorectal cancer organoids. Conclusions CEL shows a significant anti-colorectal cancer effect, potentially caused by a direct target inhibiting STAT3, inducing apoptosis, and blocking the cell cycle.

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer.@*METHODS@#A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy.@*DISCUSSION@#This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

Mini-incision with endoscope-assisted surgery for bilateral congenital second branchial cleft fistula and a pedigree report / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility and efficacy of mini-incision with endoscope-assisted resection for bilateral congenital second branchial cleft fistula, and to report on a rare pedigree. Methods: The clinical data of 5 patients with bilateral congenital second branchial fistula admitted in Fujian Provincial Hospital from April 2007 to December 2018 were retrospectively reviewed, including 2 males and 3 females, aged from 3 to 31 years old. The surgical strateges and clinical experience of single mini-incision with endoscope-assisted fistulectomy were summarized, and a rare pedigree was reported. Results: In five patients, Case 1 to Case 4 were treated with bilateral endoscopic-assisted fistula high ligation with titanium clips and removal through a single small incision under general anesthesia. No obvious complications occurred after the operation. The patients were followed up for 40-164 months with no fistula recurrence. Case 5 gave up surgical resection and was followed up for 24 months with acute infection attack once. Case 2 and Case 4 came from the same family. In this family, 7 out of 31 members of four generations had second branchial cleft fistulas, of which 4 were bilateral and 3 were right. Pedigree analysis was consistent with autosomal dominant inheritance. No deafness, preauricular tag, external and middle ear deformity and kidney malformation were found in the family members. Conclusions: Bilateral congenital second branchial cleft fistula is rare. Surgical resection is the preferred treatment. Mini-incision with endoscopic-assisted fistula high ligation with titanium clip and resection has clear operative field, ideal cosmetic effect and definite curative effect.

Prediction of perioperative hyperkalemia in dialysis patients with secondary hyperparathyroidism / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the influencing factors for serum potassium >4.4 mmol/L in the morning of parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism (SHPT). Methods: The clinical data of 72 patients with SHPT who received regular hemodialysis and underwent parathyroidectomy in Guangdong Provincial People's Hospital from January 2012 to December 2018 were analyzed retrospectively. There were 37 males and 35 females, aged from 25 to 69 years, and the dialysis timespan was from 0.5 to 11 years. The levels of parathyroid hormone, serum potassium and serum calcium before hemodialysis were examined one day before operation, and hemodialysis time and dewatering volume after hemodialysis without heparin were recorded, and also the level of serum potassium in the morning of parathyroidectomy was detected. The occurrences of hyperkalemia during and after operation were studied. The factors related to hyperkalemia in the morning of parathyroidectomy were evaluated by Pearson or Spearman correlation analysis, and the cut-off values of risk factors were calculated by receiver operating characteristic (ROC) curve. Results: Serum potassium >4.4 mmol/L in the morning of parathyroidectomy existed in 23 of 72 patients. Correlation analysis showed that serum potassium one day before operation ((4.93±0.56)mmol/L, r=0.656, P<0.001) and dehydration volume ((2.37±0.75)L, r=0.261, P=0.027) were positively correlated with serum potassium in the morning of parathyroidectomy((4.16±0.54)mmol/L). Serum potassium before hemodialysis one day before operation was a main predictor for serum potassium in the morning of parathyroidectomy (AUC=0.791, P<0.001). The cut-off value of serum potassium before hemodialysis one day before operation was 5.0 mmol/L. Conclusion: Serum potassium before hemodialysis one day before operation in patients with SHPT can predict serum potassium in the morning of parathyroidectomy, offering imformation for the safety of operation.

The Genome-Wide Changes in Expression Profile of CML T Cells After Up-regulation of TCRζ Chain Expression / 中国实验血液学杂志

OBJECTIVE@#To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ.@*METHODS@#The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3@*RESULTS@#A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated.@*CONCLUSION@#The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.

Clinical Features and Prognosis of Acute Lymphoblastic Leukemia Children with P2RY8-CRLF2 Gene Rearrangement / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement.@*METHODS@#A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification.@*RESULTS@#Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×10@*CONCLUSION@#The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.

Clinical Effect and Safety of CCLG-ALL 2008 (high risk group) Protocol in the Treatment of Childhood Mixed Phenotype Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL).@*METHODS@#The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy.@*RESULTS@#One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033).@*CONCLUSION@#The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.

Effect of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands / 华西口腔医学杂志

OBJECTIVES@#This study aims to investigate the effects of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands (SMGs) and reveal the changes in the tight junction (TJ) protein claudin-4.@*METHODS@#A total of 24 Wistar rats were randomly divided into control and irradiation groups. The irradiation groups were further divided into 1, 4, and 12 weeks groups after irradiation. One-time 20 Gy irradiation was given to the SMG area on the experimental side of the irradiation group. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs was measured using the Schirmer's test. The pathological changes in the gland tissues were observed under light microscopy after hematoxylin⁃eosin (HE) staining. The changes in the TJ ultrastructure were observed under transmission electron microscopy. The immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 receptor, aquaporin 5 (AQP5), and claudin-4 protein.@*RESULTS@#At 1, 4, and 12 weeks after irradiation, the secretion of SMGs in the irradiation group was significantly decreased and lower than that in the control group (@*CONCLUSIONS@#The changes in the TJ structure, the upregulation of the claudin-4 expression, and the damage in the paracellular pathway were involved in the hyposecretion of SMGs after irradiation.