The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

Objective:To evaluate the effect of pedicled omentum packing of pelvic floor after laparoscopic Miles precedure in the prevention of short-term postoperative complications.Methods:Seventy-two patients undergoing laparoscopic combined abdominal perineal resection for rectal cancer at He'nan Tumor Hospital from Jan 2014 to Aug 2021 were retrospectively reviewed. The observation group underwent pelvic floor reconstruction with pedicled omentum, while in control group the pelvic floor was leaving unconstructed.Results:There was no intestinal obstruction in the observation group. There were 5 cases of intestinal obstruction in the control group. Three were recovered by conservative treatment, 2 cases underwent laparotomy and 1 case underwent anastomosis between small intestine and small intestine. The incidence of intestinal obstruction between 2 groups was statistically different (0 vs. 14%, χ2=5.083, P=0.024 ). The operation time, hospital stay between the two groups were statistically different [(195±13) min vs. (159±9) min, t=10.047, P=0.000; (11.9±0.9) d vs. (14.9±2.1) d, t=-5.996, P=0.000 ). Between the two groups, there were no significant differences in the incidence of presacral infection , pulmonary infection, venous thrombosis and intraoperative blood loss (all P>0.05) . Conclusion:Pedicled greater omentum used in pelvic floor reconstruction after laparoscopic Miles procedure reduces the incidence of short-term postoperative complications, especially of intestinal obstruction.

Objective:To investigate the application value of transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position.Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 114 patients who underwent com-plete resection of presacral cyst in Henan Cancer Hospital from August 2012 to October 2021 were collected. There were 14 males and 100 females, aged (35±9)years. All patients were diagnosed as presacral cysts by preoperative magnetic resonance imaging. Of the 114 patients, 76 patients undergoing intraoperative perineal arc incision approach in the lithotomy position were divided into the innovative group, and 38 patients undergoing intraoperative Kraske approach were divided into the traditional group. Observation indicators: (1) surgical situations and specimen; (2) postoperative situations; (3) Follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical situations and specimen. The operation time, volume of intraoperative blood loss, cases with intraoperative combined transabdominal approach or sacrectomy were (137±20)minutes, (261±101)mL, 0 in the innovation group, versus (136±34)minutes, (261±116)mL, 15 in the tradi-tional group, showing no significant difference in the operation time and volume of intraoperative blood loss between the two groups ( t=0.18, 0, P>0.05) and showing a significant difference in cases with intraoperative combined transabdominal approach or sacrectomy between the two groups ( P<0.05). Results of postoperative specimen anatomy in patients of the two groups showed complete removal of the cyst. (2) Postoperative situations. The time to postoperative removing presacral drainage tube, duration of postoperative hospital stay, cases with postoperative second stage healing of incision were (11.4±2.1)days, (13.5±3.5)days, 23 in the innovation group, versus (11.5±1.9)days, (13.7±3.8)days, 4 in the traditional group, showing no significant difference in the time to post-operative removing presacral drainage tube and duration of postoperative hospital stay between the two groups ( t=-0.20, -0.24, P>0.05) and showing a significant difference in cases with postoperative second stage healing of incision between the two groups ( χ2=5.46, P<0.05). Cases with postoperative severe complications were 4 and 2 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). (3) Follow-up. All 114 patients were followed up for 48(range, 6?108)months. Cases with recurrence of cysts were 2 and 0 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). During the follow-up period, the anal defecation control function of all patients was classified as grade A?B of Williams score. Conclusions:The transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position is safe and feasible. Compared with Kraske approach, the transverse perineal arc incision approach in the lithotomy position is more suitable for patients with high presacral cyst.

Objective:To investigate the types, surgical treatments of complex intestinal fistula after radiotherapy for cervical cancer.Methods:The clinical data and treatment of 26 patients with complex intestinal fistula after radiotherapy for cervical cancer at Cancer Hospital of Zhengzhou University from Jan 2013 to Jan 2020 were reviewed .Results:Eleven patients were with recto-vaginal fistula, 1 patient with sigmoido-vesical fistula, 5 patients with combined rectal, vaginal and vesical fistula, 7 patients with low rectal fistula and peripheral infection, and 2 patients with ileo-vaginal stump fistula after radical resection of cervical cancer and adjuvant radiotherapy. All patients were underwent the surgery, including 9 patients for total pelvic or posterior pelvic resection, 6 patients for rectum or sigmoid colectomy, bladder or vaginal repair, 7 patients were done for Hartmann surgery, and 1 patient underwent segmental resection, enteroanastomosis and vaginal repair, 3 patients for transverse colostomy or proximal ileostomy. No major postoperative complications occurred . The symptoms of intestinal fistula in all patients were dissolved, and the perineal pain was significantly relieved in 23 patients. The symptoms of ileal fistula reccurred in 2 patients within 1 year after operation, and there was no mortality.Conclusions:The rectal related intestinal fistula is the most common complex intestinal fistula after radical radiotherapy for cervical cancer. The point of surgical treatment is to remove the diseased rectum or ileum.

Objective:Objective The inhibitory effect of Niuhuang Qinggan Capsule on 2019-nCoV virus was studied to provide experimental evidence for drug screening and treatment of 2019-nCoV acute respiratory disease.Methods:The 2019-nCoV virus GS048 strain was isolated and cultured by Vero-E6 cells. The solution of Niuhuang Qinggan capsule was incubated with virus in vitro to determine the change of virus titer. The effect of Niuhuang Qinggan capsule on the proliferation of 2019-nCoV virus was determined by cell culture medium method.Results:It was found that the concentration of 274.3 μg/ml was not toxic to the cells when the concentration of drugs was lower. When the drug was incubated with virus, the titer of virus decreased from 10 4.4TCID 50/ml to 10 2.8TCID 50/ml. In vitro 2019-nCoV virus culture experiment showed that the addition of the drugs reduced the cytopathy, and the logarithmic value of virus titer decreased by 40% -50%. Conclusion:In this study, in vitro inhibition experiments suggest that Niuhuang Qinggan capsule has the potential to inhibit the proliferation of 2019-nCoV. It can be used as a candidate drug to further verify the therapeutic effect of the 2019-nCoV acute respiratory disease.

Endophytic fungi are promising producers of bioactive small molecules. Bioinformatic analysis of the genome of an endophytic fungus

Objective:To compare the clinical utility of 18F-fibroblast activating protein inhibitor (FAPI)-42 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in newly diagnosed lung cancer patients. Methods:From May 2020 to September 2021, the images of 43 lung cancer patients (32 males, 11 females, age: 37-80 years) who pathologically confirmed and received 18F-FDG and 18F-FAPI-42 PET/CT within 2 weeks in the First Affiliated Hospital of Guangzhou Medical University were prospectively analyzed. The maximum standardized uptake value (SUV max) of 18F-FDG and 18F-FAPI-42 and the number of lesions detected by 2 imaging methods were compared by using paired t test and Wilcoxon rank sum test. Results:The 43 newly diagnosed lung cancer patients included 35 adenocarcinoma, 2 squamous cell carcinoma, 4 small cell lung cancer, and 2 high-grade neuroendocrine tumors. 18F-FAPI-42 had a very high tumor uptake (SUV max: 12.24±3.97) and lesion detection rate (positive rate: 100%(37/37)) in primary lung adenocarcinoma and squamous cell carcinoma. The uptake of 18F-FAPI-42 in lymph node (10.13±5.43), pleura (6.75(4.96, 8.58)) and bone lesion (7.18(4.33, 9.66)) were significantly higher than those of 18F-FDG (6.35±3.30, 2.69(1.81, 5.00), 4.38(2.96, 6.36); t=12.19, z values: 5.47, 5.79, all P<0.001). In lung adenocarcinoma and squamous cell carcinoma, although the uptake of 18F-FAPI-42 in brain metastases was significantly lower than that of 18F-FDG (0.72(0.15, 1.82) vs 6.53(4.65, 9.34); z=6.42, P<0.001), the tumor/background (T/B) ratio was significantly higher than that of 18F-FDG (3.54(1.15, 14.88) vs 0.96(0.77, 1.04); z=6.05, P<0.001). In lung adenocarcinoma and squamous cell carcinoma, the number of lesions detected by 18F-FAPI-42 PET/CT was significantly more than that of 18F-FDG (lymph node: 6.0(2.3, 11.5) vs 4.5(2.0, 10.8); brain: 2.0(1.0, 3.0) vs 0.0(0.0, 0.0); pleura: 6.0(2.8, 10.0) vs 4.0(0.8, 5.5); z values: 2.16, 3.10, 2.04, all P<0.05). However, in high-grade neuroendocrine tumors and small cell lung cancer, the SUV max of 18F-FAPI-42 in primary lesions (8.05±2.60), lymph node lesions (5.98±2.21) and brain lesions (0.44(0.13, 0.82)) were lower than those of 18F-FDG (16.28±5.17, 12.30±5.47, 4.94(4.84, 6.25); t values: 3.58, 7.52, z=3.06, all P<0.05). Conclusions:In lung adenocarcinoma and squamous cell carcinoma, 18F-FAPI-42 has a very high tumor uptake and lesion detection rate in primary tumor. In addition, compared with 18F-FDG PET/CT, 18F-FAPI-42 PET/CT shows clearer tumor contours and more lesions. Therefore, 18F-FAPI-42 is more suitable for preliminary staging of lung adenocarcinoma and squamous cell carcinoma than 18F-FDG, while the opposite is true in small cell lung cancer and high-grade neuroendocrine tumors.

Objective:To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors.Methods:The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management.Results:Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed.Conclusion:Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.