The most toxic DNA damage is DNA double strand breaks (DSBs), which are mainly repaired by non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) belongs to phosphatidylinositol-3-kinase-related protein kinase family (PIKK) and plays a key role in NHEJ. DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence, development and drug resistance of malignant tumors. In this article, the representative DNA-PK inhibitors with anticancer effects are reviewed, in order to provide a reference to discovery novel DNA-PK inhibitors.

BACKGROUNDIntracranial infection is one of the most common complications of open craniocerebral injury and of conventional craniotomy in neurosurgery. The presence of blood-brain barrier leads to lower drug concentrations in the cerebrospinal fluid than in the venous blood. Increasing the intravenous dosage or frequency carries the risk of systemic adverse reactions or infections in other parts of the body. Developing an artificial dura mater (ADM) for sustained antibiotic release for use during neurosurgery can solve the problems perfectly.

METHODSThree types of drug-loaded ADMs made of collagen and containing cefuroxime sodium, ceftriaxone sodium, or norvancomycin were prepared. The antibacterial activity and sustained release characteristics of the ADMs were examined using bacteriostatic and release tests.

RESULTSSingle-layered collagen based ADMs (40 mm×50 mm×5 mm) containing 18 mg cefuroxime sodium or ceftriaxone sodium were not suitable for continued development because of drug preservation and stability issues. Using smaller ADMs (20 mm×30 mm×7 mm), containing 4.86 mg of norvancomycin, with increased collagen density and a three-layered film with two outer drug-free films above and below the antibiotic layer resulted in sustained cumulative release of 2.91 mg (59.9%) of norvancomycin over 72 hours. The similar factor (f2) comparison method proved that products from a same batch were statistically significant similar (f2 > 50).

CONCLUSIONSArtificial ADMs made of collagen can be processed to provide a mature dural repair material for the sustained release of norvancomycin. This system may provide a basis for developing sustained release materials for other drugs.

Anti-Bacterial Agents ; chemistry ; Biocompatible Materials ; chemistry ; Ceftriaxone ; chemistry ; Cefuroxime ; chemistry ; Collagen ; chemistry ; Dura Mater ; chemistry ; Vancomycin ; analogs & derivatives ; chemistry

Objective To analyze the NBS-LRR disease resistance gene family of Codonopsis pilosula(Franch.)Nannf.and explore the disease resistance mechanism,so as to solve the problem of root rot disease of C.pilosula and promote the breeding and industrial development of C.pilosula.Methods Based on the transcriptome data of C.pilosula in response to root rot pathogen,gene structure,phylogeny,gene interaction and expression pattern of C.pilosula NBS-LRR family genes were analyzed by using bioinformatics methods.Results 88 NBS-LRR family genes were successfully identified.Including N,NL,CN,CNL,TN,TNL and PN,there are 50,14,1,14,4,3 and 2 genes respectively.Their physical and chemical properties,gene structure,phylogeny,gene interaction and expression pattern were analyzed.The results showed that CNL subfamily genes of C.pilosula were amplified during evolution;CNL and TNL gene structures ar-relatively conservative;Expression pattern analysis showed that there were differences in temporal expression patterns of C.pilosula NBS-LRR family genes under F.oxysporum infection.The highly expressed genes DN64786c1g6,DN64786c1g5,DN48234c0g2,DN54844c1g2,DN59747c0g3,DN56071c1g8,DN64591c1g1,DN48464c1g1,DN59886c0g1 play an important role in regulating the disease resistance of C.pilosula.The DN54844c1g2 may interact with GLR family,and then participate in immune regulation by regulating Ca2+ influx;DN64786c1g5 may interact with cytc-1 and cytc-2,and then participate in the response of C.pilosula to root rot by participating in redox reaction;DN59747c0g3 may interact with MPK3 and play an important role in the response of C.pilosula to root rot by participating in map signal cascade,phosphorylating WRKY transcription factor and participating in hypersensitivity reaction(HR).Conclusion The identification and expression analysis of NBS-LRR family genes of C.pilosula is of great significance to explore the mechanism of root rot resistance and gene function of C.pilosula..

The Acute Disease Quality Initiative advocates multidisciplinary care for the survivors of acute kidney injury (AKI). The bundled care strategy recognizes the role of pharmacists. However, their specific contributions in this context remain underexplored. Methods: This retrospective study examined the efficacy of pharmacist-led post-AKI pharmaceutical care in outpatient settings at a single center. Adults with recent AKI during hospitalization, maintaining an estimated glomerular filtration rate <45 mL/min/1.73 m2 postdischarge, were enrolled in a multidisciplinary team care program from March 2022 to January 2023, with a 6-month follow-up period. Pharmacist-delivered care adhered to international multidisciplinary consensus guidelines. Efficacy was evaluated by analyzing medication-related recommendations, medication adherence, nephrotoxic drug utilization, and renoprotective medication usage before and after the intervention. Results: A total of 40 patients were referred to the pharmacist-managed clinic. Of these, 33 patients (mean age, 63 ± 15 years; 60.6% male) attended the clinic. Nineteen patients completed follow-up visits. The pharmacist provided 14 medication-related recommendations to relevant physicians, with 10 of these recommendations (71.4%) being accepted. There was a significant decrease in the use of modifiable nephrotoxic drugs (p = 0.03). However, no significant improvements were noted in medication adherence or the utilization of renoprotective medications. Conclusion: Our study underscores the potential benefits of pharmacist-led post-AKI bundled care strategy in outpatient settings. We observed a significant reduction in the utilization of modifiable nephrotoxic drugs, indicating the effectiveness of pharmacist interventions in optimizing medication regimens to mitigate renal harm.

BACKGROUNDTuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs.

METHODSTotally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed.

RESULTSVisual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤ 8 cm/s, the visual outcome would be better.

CONCLUSIONSThe surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤ 8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs.

Adult ; Aged ; Female ; Humans ; Male ; Meningeal Neoplasms ; pathology ; surgery ; Meningioma ; pathology ; surgery ; Middle Aged ; Neurosurgical Procedures ; methods ; Retrospective Studies ; Sella Turcica ; pathology ; surgery ; Skull Base Neoplasms ; pathology ; surgery ; Visual Acuity

OBJECTIVETo detect the RNA of severe acute respiratory syndrome virus (SARS-CoV) by using reverse transcription polymerase chain reaction (RT-PCR) targeted for a two loci and a modified nested real-time RT-PCR as to improving the reliability and sensitivity of tests.

METHODSA nested RT-PCR was used for detecting one fragment of SARS-CoV RNA in oropharyngeal swabs from 3 SARS probable patients, 4 SARS suspect patients and other 27 patients with fever in Hangzhou, and the nested RT-PCR product from one SARS probable patient was sequenced. Meanwhile in these 3 SARS probable patients, other three RT-PCR methods, including a hemi-nested RT-PCR targeted for another fragment of SARS-CoV RNA, a real-time RT-PCR and a modified nested real-time RT-PCR, were employed to detect SARS-CoV RNA.

RESULTSTwo positives were found in the 3 SARS probable patients, and none positive in 4 SARS suspect patients and other 27 patients with fever, using the nested RT-PCR. The sequence of the nested RT-PCR product from one SARS probable patient was identified with the counterpart of SARS-CoV genomes published in public database. The results of the hemi-nested RT-PCR, the real-time RT-PCR and the modified nested real-time RT-PCR in the 3 SARS patients were consistent with the one of the nested RT-PCR. During detecting specimen with low copies of RNA, a weak positive signal was produced after about 35 cycles in the real-time RT-PCR, but a strong positive signal was found only after 10 cycles in the modified nested real-time RT-PCR.

CONCLUSIONIt might improve the reliability of test by employing RT-PCR targeted for two or more fragments in SARS-CoV genome. The modified nested real-time RT-PCR might have higher sensitivity than the routine real-time RT-PCR.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Humans ; Middle Aged ; RNA, Viral ; genetics ; metabolism ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; SARS Virus ; genetics ; Sensitivity and Specificity ; Severe Acute Respiratory Syndrome ; diagnosis ; virology ; Young Adult

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Objective To analyze the clinical features and prognosis of adult optic neuritis patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-ON) or aquaporin 4 antibody (AQP4-ON).Methods A retrospective study. From December 2015 to February 2018, in the Beijing Chaoyang Hospital of Capital Medical University and Chinese PLA General Hospital, 162 eyes of 132 patients with positive serum MOG antibody and AQP4 were included in the study. There were 42 MOG-ON patients (49 eyes, 31.8％), 90 AQP4-ON patients (113 eyes, 68.2％). The clinical features of optic neuritis (annual recurrence frequency, incidence of optic disc edema), brain and optic nerve enhanced MRI, serum autoimmune antibodies and cerebrospinal fluid test results were compared between MOG-ON and AQP4-ON patients. All patients were treated with intravenous methylprednisolone sodium succinate in the acute phase and then switched to oral prednisone acetate tablets. The average follow-up time was 15 months. The glucocorticoid dependence, visual prognosis, spinal cord symptoms, and myelitis at the last follow-up were comparatively analyzed between MOG-ON and AQP4-ON patients. The comparison of the count data was performed by χ2 test, and the measurement data were compared byt test.Results Compared with AQP4-ON patients, MOG-ON patients had higher annual recurrence frequency (t=3.760,P=0.005), higher incidence of optic disc edema (χ2=14.777,P<0.001), higher incidence of hormone dependence (χ2=25.496,P<0.001), and better visual prognosis (χ2=28.759, P<0.001). MOG-ON patients were more likely to involve the optic nerve, AQP4-ON patients were more likely to involve the optic chiasm and the optic tract. There was a significant difference in the location of lesions between MOG-ON and AQP4-ON patients (χ2= 5.447,P= 0.015). The proportion of AQP4-ON patients with autoimmune antibodies was significantly higher than that of MOG-ON patients (χ2 = 20.453,P<0.001). The results of cerebrospinal fluid test showed that the white blood cell count of patients with MOG-ON and AQP4-ON were within the normal range, but the IgG level of AQP4-ON patients was significantly higher than that of MOG-ON patients (t=8.669,P<0.001). At the last follow-up, there were 7 and 29 patients of myelitis in MOG-ON and AQP4-ON patients respectively (χ2=3.494,P=0.046).Conclusions The clinical characteristics of MOG-ON were different from AQP4-ON. The incidence of optic disc edema and recurrence rate were higher, but the proportion of autoimmune antibodies was lower. MOG-ON was more likely to show hormone dependence, but the visual prognosis was better. AQP4-ON was easily involved in optic chiasm and optic tract, and the incidence of myelitis was higher.

Objective: To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive. Methods: Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Children's Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis. Results: TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3%) ≥10 years old. At initial diagnosis, 33 patients (60.0%) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count ≥50×10⁹/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases(32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10^-4, 12 patients (21.8%) had MRD≥10^-4 and MRD<10^-2, 1 patient (1.8%) had MRD≥10^-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P < 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10^-3 group and MRD≥10^-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10^-3 group and MRD≥10^-3 group (P < 0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS (OR= 2.971, 95% CI 1.330-6.633, P= 0.008; OR= 2.884, 95% CI 1.295-6.419, P= 0.009). Conclusions Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis.

OBJECTIVETo investigate the effects of surgery treatment on serious penile lesions and malformation.

METHODSSixty-two patients, aged from 19 to 63 years old (mean 35 ys), were included in the study. Among them, 4 patients suffered from penis partial defection were respectively treated with restoring defective penis, penis lengthening and urethroplasty; three patients with penis completely missing were treated with penis reconstruction surgery; 22 cases with serious penile curvature were treated with the 16-dot plication technique (Lue's procedure); 15 cases with penile fracture were treated with conservative treatment for 1 case and with patch penis, corpus spongiosum, and deep penile dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3-pieces of penile prosthesis, including the prosthesis perforating to the urethra, water pump failure, broken connection tube, erection angle < 60 degrees and failure to expansion the corpus cavernosum, were treated by taking out prostheses, urethral repair cracks, replacement of the prostheses, excision of fibrosis scar and re-implantation prostheses respectively. Four cases with penis complete amputation were treated with the penis replantation; three cases of avulsion injury were treated with the replantation and free flap skin; 6 with Paget's disease of penises were treated with the lesion free skin buried in the scrotum and penis.

RESULTSAll these patients were followed up for 3 months to 4 years, with the average of 9 months. Among the 4 cases of penis partial defection, 2 patients were satisfied with the penile appearance and sexual function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the loss of the penis completely were satisfied with both the postoperative appearance and urination, and 1 was not satisfied. Twenty-two cases of penile curvature deformities were corrected, and one case was recurrence. Fourteen of the 15 patients with penile fracture were followed, and all got the restoration of sexual function. Among them, 5 cases with post-operative complications, including mild bending, algopareunia, subcutaneous induration, poor hardness and poor sexual pleasure, were not further treated, and another case lost; Five cases with post-operative complications of three-pieces penile prosthesis were treated successfully, and 4 of their spouses were satisfied with their sexual function after operation, only 1 of their spouse not satisfied. Among four cases with complete amputation of penis, two cases of penis were replanted successfully while two necrosis. Three cases with avulsion were treated with skin grafting successfully. All 6 cases with penile Paget's disease were followed for 2 -4 years, and free skin grafts were all survival. One patient died of brain metastases 18 months after operation and five cases were disease-free survival.

CONCLUSIONThe patients should be treated based on the procedure of andrological and urological surgery, together with microsurgical, flap or skin graft technique. The urologist should design personalized surgical procedure. Most of the patient's penis shape and erectile dysfunction can be reconstructed by our procedures, but some patients can not achieve the desired appearance or function of penis. New approaches of the treatment ought to be developed to restore both of the shape and function for those severe injury of the penis.

Adult ; Humans ; Male ; Middle Aged ; Penile Implantation ; Penile Prosthesis ; Penis ; injuries ; surgery ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; Urologic Surgical Procedures, Male ; methods ; Young Adult