ObjectiveRoot rot is one of the most serious diseases in the cultivation and production of Atractylodes lancea. Trichoderma spp. are effective in the biocontrol of root rot without causing environmental pollution. This study aims to isolate and study a Trichoderma strain capable preventing and controlling root rot from the rhizosphere of A. lancea and to solve the problem of disease prevention and control in the planting and production of A. lancea. MethodTrichoderma T2204 was isolated by the dilution-coating method and identified by ITS sequencing. The inhibitory activities of T2204 and its volatiles against two pathogenic fungal strains were examined by dual-culture and co-culture experiments. The biocontrol potential of T2204 on root rot of A. lancea and the effect of T2204 on the accumulation of medicinal compounds in the rhizosphere of A. lancea were investigated by pot experiments and GC-MS， respectively. In addition， the optimal medium， photoperiod， temperature， pH， and carbon and nitrogen sources for the culture of T2204 were explored. ResultThe Trichoderma isolate T2204 was identified as T. citrinoviride and had direct inhibitory effects on two highly pathogenic strains causing root rot. In the dual-culture experiments with the two pathogenic strains， T2204 showcased the inhibition rates of 77.90% and 76.80%， respectively. In the co-culture experiments with the two pathogenic strains， the volatile organic compounds produced by T2204 showed the inhibition rates of 57.11% and 81.11%， respectively. The pot experiments showed that the survival rate of A. lancea seedlings infected by root rot reached 100% after inoculation with T2204 and was only 50% in the case without inoculation of T2204. After 150 days of cultivation， the dry weight and atractylodin content of the rhizome of A. lancea plants treated with T2204 increased by 32% （P<0.05） and 11%， respectively， compared with the untreated group. The optimal conditions for the growth of T2204 were PDA or PSA medium， photoperiod of 12 h dark/12 h light， 25-30 °C， pH 5-6， carbon sources of glucose， D-fructose， soluble starch， and maltose， and the nitrogen sources of ammonium sulfate and ammonium dihydrogen phosphate. The optimal conditions for the sporulation of T2204 were PSA or CMA medium， photoperiod of 12 h dark/12 h light， 20-30 °C， pH 8， carbon source of sucrose， and nitrogen source of sodium nitrate. ConclusionT2204 could improve the growth and root rot resistance of A. lancea and promote the accumulation of medicinal compounds. The findings laid a foundation for the industrialized production and application of T2204 in the production of A. lancea in the future.

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.
Humans ; Neoadjuvant Therapy/methods* ; Margins of Excision ; Treatment Outcome ; Rectal Neoplasms/pathology* ; Rectum/pathology* ; Neoplasm Staging ; Retrospective Studies

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.
Mice ; Animals ; Humans ; MicroRNAs/metabolism* ; Exosomes/genetics* ; Sincalide/metabolism* ; Pancreatic Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/genetics* ; Mesenchymal Stem Cells/metabolism* ; Umbilical Cord

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Objective:To investigate the causes and prognosis of salvage cholecystectomy for relapsing cholecystolithiasis after gallbladder-preserving gall stones removal surgery.Methods:From Jul 2015 to Dec 2019, 24 referral patients with gallstone recurrence after gallbladder-preserving cholelithotomy surgery received salvage cholecystectomy. The clinical data was analyzed to explore the causes for re-operation and the prognosis.Results:Twenty-two cases had definite gallstone recurrence, among them 19 cases were symptomatic, 2 cases were operated on suspected gallbladder tumor and common bile duct stones induced acute cholangitis. Laparoscopic cholecystectomy was successfully performed in 23 cases and 1 case was converted to open surgery. No severe complication were observed in all the patients.Conclusions:Symptomatic gallstone recurrence is the most common causes of salvage cholecystectomy after gallbladder-preserving cholelithotomy. Laparoscopic surgery procedure is still highly successful.

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
Lipid Metabolism/genetics* ; Mendelian Randomization Analysis ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Triiodothyronine

Objective    To develop a novel methylene blue staining technique to localize small esophageal leiomyomas ( small esophageal leiomyomas ( and 4 females with an average age of 51 years. We preoperatively injected 0.5–1.0 ml methylene blue in the submucosa adjacent to the tumors under the guidance of gastroscope. Then, we transferred the patients to the operating room. Results    Staining was successful in 9 patients. The unstained tumor was exposed after the blue-stained mediastinal pleura and overlying muscle were incised longitudinally during ideo-assisted thoracoscopic surgery via one utility port. No abnormalities were detected in the esophageal mucosa. No major complications, such as esophageal leakage or esophageal diverticulum occurred. Conclusion    Endoscopic methylene blue staining is safe and feasible for localizing small esophageal leiomyomas during video-assisted thoracoscopic surgery via one utility port. This method will enable enucleation precise and easy.

BACKGROUNDHigh rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM.

METHODSA total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6-24 months, were consecutively enrolled. Patients' demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients.

RESULTSFinally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03-1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24-7.34, P = 0.015).

CONCLUSIONThe elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.

Objective To investigate the treatment and disposal of laboratory animal waste in Beijing area in 2016. Methods Questionnaire, telephone survey, on-the-spot investigation and WeChat were used to survey the basic situation and laboratory animal waste management, including bedding material, excreta, carcasses and experimental consumables,etc. in 164 laboratory animal facilities in Beijing area in 2016. Results The data we have collected were relatively comprehensive and universal, reflecting the currently existing problems. Conclusions This investigation provides a reference for the compilation of the management rules of laboratory animal waste in Beijing.