Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:To evaluate the efficacy of total laparoscopic surgery vs. open surgery for hilar cholangiocarcinoma. Methods:The clinical data of 45 patients undergoing laparoscopic radical resection of hilar cholangiocarcinoma and 42 patients by open surgery from Mar 2017 to Mar 2021 were retrospectively analyzed.Results:There was no significant difference in demographics, Bismuth classification and excision extension between the two groups (all P>0.05). The laparoscopic surgery used longer time ( t=-1.366, P<0.05). The intraoperative blood loss, number of lymph node dissection and postoperative hospital stay favored laparoscopic method( t=0.043, t=0.026, t=-1.852, P<0.05). R 0 radical resection rate，postoperative complications were also in favor of laparoscopic surgery ( χ2=3.216, χ2=2.566, all P<0.05). There was no significant difference in postoperative pathology and in hospital expenses (all P>0.05). The 1- and 3-year survival rate of the laparoscopic group was superior (all P<0.05). Conclusions:In spite of longer operational time，patients in laparoscopic hilar cholangiocarcinoma radical resection group have shorter postoperative in hospital stay and longer postoperative survival time.

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Objective:To analyze the ultrasonographic features of adenoma of the nonpigmented ciliary epithelium (ANPCE).Methods:A retrospective series of case studies. From January 2014 to October 2021, 31 patients (31 eyes) with ANPCE (ANPCE group) were diagnosed in the eye center of Beijing Tongren Eye Center of Beijing Tongren Hospital, Capital Medical University, and 17 patients (17 eyes) with ciliary body melanoma (control group) diagnosed at the same time were selected as the control group. There was no significant difference in age ( t=-0.564) and sex composition ratio ( χ 2=0.182) between the two groups ( P=0.576, 0.670). All patients underwent ultrasound biomicroscopy to obtain the measurement parameters: tumor height, maximum basal diameter, maximum diameter, ratio of maximum diameter to basal diameter and ratio of maximum diameter to height; tumor location, shape, internal echogenicity intensity, echogenicity uniformity, degree of sound attenuation, invasion of iris, anterior displacement of the iris, lens subluxation were observed. The measurement parameters and observation indexes of the two groups were compared by independent sample t-test and χ 2 test. Receiver operating characteristic (ROC) curve was drawn, area under the ROC curve (AUC) was determined, and parameter indicators with differential diagnosis value were screened. Results:The maximum diameter, height, maximum basal diameter, ratio of the maximum diameter to the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumors in the ANPCE group and the control group were 5.64±0.98 mm, 4.24±0.59 mm, 3.66±0.71 mm, 1.58±0.34, 1.34±0.19 and 7.82±2.03 mm, 4.47±2.44 mm, 7.02±1.96 mm, 1.13±0.16, 2.09±1.06. The maximum diameter, the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumor in the ANPCE group were all smaller than those of the control group, and the ratio of the maximum diameter to the maximum basal diameter was greater than that of the control group, and the differences were statistically significant ( t=-4.159,-6.808, -2.924, 6.257; P<0.05). The tumors in the ANPCE group were mainly spherical (87.1%, 27/31), with no significant acoustic attenuation (77.4%, 24/31), less invading the root iris (77.4%, 24/31), and the tumors were mostly located in the ciliary body coronal (74.2%, 23/31); tumors in the control group were mainly hemispherical (47.1%, 8/17) or spherical (47.1%, 8/17), with significant sound attenuation (76.5%, 13/17), most of the tumors invaded the iris (70.6%, 12/17), and the tumors were mostly located from the pars plana to the coronal (76.5%, 13/17). There were statistically significant differences in the position, shape, sound attenuation degree, and whether it invaded the iris between the two groups of eyes ( χ 2=15.132, 19.767, 13.118, 10.581; P<0.05). The results of ROC curve analysis showed that the ratio of the largest diameter to the largest base diameter, the degree of sound attenuation and the AUC of whether the iris was violated were higher, which were 0.881, 0.769, and 0.740, respectively. Conclusions:Ultrasound biomicroscopy is helpful in the diagnosis and differential diagnosis of ANPCE and ciliary body melanoma. The ratio of maximum diameter to maximum basal diameter, the degree of sound attenuation and whether it invades the root iris are important parameters to distinguish the two tumors.

Objective:To compare the embedding anastomosis with the intermittent eversion anastomosis on the pancreatic fistula rates after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 116 patients who underwent LPD at the Center Hospital of Xianyang City affiliated to Xi' an Jiaotong University Health Science Center from March 2016 to March 2020 were retrospectively studied. According to the method of pancreaticojejunostomy used, these patients were divided into the following two groups: the embedding anastomosis group ( n=55) and the intermittent eversion anastomosis group ( n=61). The duration of pancreaticojejunostomy, bilioenterostomy and gastrointestinal anastomoses, and the amounts of intraoperative blood loss and postoperative complication rates were compared between the two groups. Results:Of 116 patients in this study, there were 67 males and 49 females, with a median age of 61.5 years. No perioperative death occurred in the 2 groups. The operation time, digestive tract reconstruction time and pancreaticojejunostomy time in the embedded anastomosis group were (260±20), (65±15) and (35±15) min, respectively, which were significantly lower than those in the intermittent eversion anastomosis group (305±25), (81±25) and (45±12) min, (all P<0.05). The grade A and B pancreatic fistula rates in the embedded anastomosis group were 27.3%(15/55) and 21.8%(12/55), respectively, which were significantly higher than those in the intermittent eversion anastomosis group [8.2%(5/61) and 6.6%(4/61)], (all P<0.05). The postoperative hospital stay in the intermittent eversion anastomosis group (10.3±1.1) d was significantly lower than that in the embedding anastomosis group [(15.2±3.2) d, P<0.05]. Conclusion:In LPD, when compared with embedded pancreaticojejunostomy, intermittent eversion pancreaticojejunostomy reduced the postoperative pancreatic fistula rate and shortened the postoperative hospital stay.

AIM: To demonstrate the effects of telmisartan on the proliferation and apoptosis of U937 cells.METHODS: The proliferation ability of the U937 cells was assessed by CCK-8 assay and colony formation test with methylcellulose.The CD11b expression rate of the U937 cells was identified by flow cytometry.The apoptotic rate was analyzed by flow cytometry with Annexin V-PI double staining and Hoechst 33342 staining.The protein levels of cleaved PARP and cleaved caspase-3 were determined by Western blot.RESULTS: The results of CCK-8 assay confirmed that the viability of U937 cells was inhibited by telmisartan.The colony formation capacity of U937 cells was also significantly inhibited by telmisartan.The differentiation of U937 cells was induced by telmisartan with the expression of CD11b.The results of flow cytometry analysis with Annexin V-PI double staining and Hoechst 33342 staining identified that the apoptosis of U937 cells was induced by telmisartan in dose-dependent and time-dependent manners with the up-regulation of cleaved PARP and cleaved caspase-3 proteins.CONCLUSION: Telmisartan inhibits the proliferation and induces the differentiation of U937 cells.Telmisartan also induces the apoptosis of U937 cells through the caspase pathway.

OBJECTIVETo investigate the apoptosis inducing effects of ponicidin (PON) on leukemic K562 cells and its mechanisms of action.

METHODK562 cells in culture medium in vitro were given different concentrations of PON (10-50 micromol x L(-1)) for 24, 48 and 72 h. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rates were detected by flow cytometry (FCM) using Annexin V staining after K562 cells were treated with different concentrations of PON for 72 hours, and cell morphology was observed by Wright-Giemsa staining. Western blot was used to detect caspase-3 and poly(ADP-ribose) polymerase (PARP) expression, and the protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) as well as p-AKT and p-P85 in PI3K/AKT signaling pathways were also detected.

RESULTPON (over 30 micromol x L(-1)) could inhibit the growth of K562 cells in both time- and dose-dependent manner. FCM analysis revealed that apoptotic cells were gradually increased in a dose-dependent manner after treatment for 72 hours, and that marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Wright-Giemsa staining after treatment by 50 micromol x L(-1) PON. Western blot showed cleavage of the caspase-3 zymogen protein (32 kD), with the appearance of its 17 kD subunit, and a cleaved 89 kD fragment of 116 kD PARP was also found. Furthermore, Western blotting also showed that expression of p-AKT and p-P85 in PI3K/AKT signaling pathways was downregulated dramatically whereas the expression of p-P38 as well as p-ERK and p-JNK remained unchanged after the cells were treated by PON for 48 h.

CONCLUSIONThe results demonstrate that PON exhibits in vitro anti-leukemia effect by induction of apoptosis in K562 cells, and that PON induced apoptosis in K562 cells mainly related to activation of caspase-3 as well as inactivation of PI3K/AKT signaling pathway via down regulation of the expression of p-AKT and p-P85 protein levels. These results provide strong laboratory evidence for further anti-leukemia trials of PON.

Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Humans ; Poly(ADP-ribose) Polymerases ; metabolism ; Signal Transduction ; drug effects

Objective To investigate the apoptosis inducing effects of oridonin on leukemic THP-1 cells and its mechanisms of action. Methods THP-1 cells in culture medium in vitro were given different concentrations of oridonin (16～56 μmol/L) for 24, 48 and 72 h. The inhibitory rate of the cells were measured by MTT assay, apoptotic morphology was observed by Hoechst 33258 staining, and Annexin V/PI staining was used to detect cell apoptosis by flow cytometry (FCM). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression were detected by Western blotting. Results Oridonin (over 32 μmol/L) could inhibit the growth of THP-1 cells and cause apoptosis remarkably, the suppression was both in time-and dose-dependentmanner. Marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Hoechst 33258 staining, and Annexin V/PI staining showed that apoptotic cells gradually increased after the cells treated with oridinon. Western blotting showed cleavage of the caspase-3 zymogen protein (32×103), with the appearance of its 20×103 subunit, and a cleaved 89×103 fragment of 116×103 PARP was also found. Conclusion Oridonin can inhibit cell growth and induce apoptosis in THP-1 cells via activation of caspase-3. The results indicated that oridonin might be an important potential anti-leukemia reagent.

Objective To investigate the apoptosis inducing effect of peroxisome proliferator-activated receptor r(PPARr)agomst on leukemic K562 cells and its mechanisms of action.Methods K562 cells in culture medium in vitro were given different concentrations of PPARragonist rosiglitazone(RGZ)(20-80 umol/L)for O,24,48 and 72h The inhibitory rate of the cells were measured by MTT assay,cell apoptosis was detected by Annexin V/PI staining,and the expression of P53 protein as well as the activity of caspase-3 were also detected.Results RGZ(over 40umoL/L)could inhibit the growth of K562 cells and cause apopto-sis remarkably,the suppression Was both in time-and dose-dependent manner.The expression of P53 pmtein was upregulated and the activity of caspase-3 Was increased concomitantly after the cells werle treated by RGZ.Conclusion PPARr agonist RGZ(over 40 umol/L)can induce apoptosis on K562 cells signifieantly,upregu-lation the expression of P53 protein as well as increasing caspase-3 activity may be one of its most important mechamisms.

The effects of protein kinase C (PKC) on the tension and the activity of voltage-dependent delayed rectifier potassium channel (K(y)) were examined in normal and passively sensitized human airway smooth muscle (HASM), by measuring tones and whole-cell patch clamp techniques, and the K(v) activities and membrane potential (E (m)) were also detected. The results showed that phorbol 12-myristate 13-acetate (PMA), a PKC activator, caused a concentration-dependent constriction in normal HASM rings. The constriction of the passively sensitized muscle in asthma serum group was significantly higher than that of the normal group (P<0.05), and the constrictions of both groups were completely abolished by PKC inhibitor Ro31-8220 and calcium channel inhibitor nifedipine. K(v) activities of HASM cells were significantly inhibited by PMA, and the E (m) became more positive, as compared with the DMSO (a PMA menstruum)-treated group (P<0.01). This effect could be blocked by Ro31-8220 (P<0.01). It was concluded that activation of PKC could increase the tones of HASM, which might be related to the reduced K(v) activity. In passively sensitized HASM rings, this effect was more notable.