Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Along with the reforms of the assessment and approval regime for new drugs in China in recent years, independently researched and developed innovative drugs and conditionally approved drugs in China have been more and more. The pre-market clinical trials, assessment and approval system (especially the conditional approval system), and post-market monitoring and management of new drugs in China are still in a continuous improvement stage. Thus we need to specially pay attention to the safety of innovative drugs that independently developed in China and do a good job in post-marketing safety supervision. More evidence-based information for safe use of this type of medication in patients can be provided through the following aspects: strengthening the drug safety monitoring, conducting systematic evaluation of literature data, widely collecting drug safety data through high-quality real-world research, and conducting in-depth mining of information from drug safety reports.

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Along with the reforms of the assessment and approval regime for new drugs in China in recent years, independently researched and developed innovative drugs and conditionally approved drugs in China have been more and more. The pre-market clinical trials, assessment and approval system (especially the conditional approval system), and post-market monitoring and management of new drugs in China are still in a continuous improvement stage. Thus we need to specially pay attention to the safety of innovative drugs that independently developed in China and do a good job in post-marketing safety supervision. More evidence-based information for safe use of this type of medication in patients can be provided through the following aspects: strengthening the drug safety monitoring, conducting systematic evaluation of literature data, widely collecting drug safety data through high-quality real-world research, and conducting in-depth mining of information from drug safety reports.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R²=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.
Humans ; Microfluidics ; Immunoglobulin G ; Kidney ; Microfluidic Analytical Techniques

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective To analyze the independent risk factors and complications for perioperative hyperbilirubinemia in Stanford type A aortic dissection undergoing operation and investigate the management strategy of perioperative hyperbilirubi-nemia. Methods Between January 2013 and January 2018 from the department of great vessel surgery of heart centre of,290 cases of patients with Stanford type A aortic dissection undergoing operation were collected consecutively,male 210 cases,fe-male 80 cases. The related data and perioperative peak hyperbilirubinemia were recorded. According to the perioperative peak hyperbilirubinemia,patients were divided into 2 groups:≥51. 3 μmol/ L group and < 51. 3 μmol/ L group. Univariate and lo-gistic regression analysis were used to identify the independent risk factors. The perioperative complications were also recorded. Results Preoperative total bilirubin ≥ 17. 1 μmol/ L(OR = 2. 105,95％ CI: 1. 153 - 3. 125,P = 0. 016),cardiopulmonary bypass time > 3. 5 h(OR = 1. 103,95％ CI: 1. 316 - 6. 151,P = 0. 031),a large number of hemolysis(OR = 1. 503,95％CI: 1. 506 - 6. 651,P = 0. 029),the input amount of 24 h allogeneic red blood cell > 2000 ml(OR = 1. 381,95％ CI:0. 956 - 2. 552,P = 0. 036)were the independent risk factors for perioperative hyperbilirubinemia. The incidence rate of post-operative acute hepatic failure(2. 5％ vs. 0,P = 0. 021)and artificial liver therapy(2. 5％ vs. 0,P = 0. 021)in≥51. 3μmol/ L group were significantly increased. The incidence rate of postoperative acute lung injury(37. 5％ vs. 25. 2％,P =0. 039)and acute kidney injury(38. 7％ vs. 19. 5％,P = 0. 035)in 51. 3 μmol/ L group were also significantly increased. The duration of mechanical ventilation[(4. 1 ± 1. 6)days vs. (2. 8 ± 1. 3)days,P < 0. 05]and ICU stay time[(5. 1 ± 2. 3)days vs. (3. 9 ± 1. 8)days,P = 0. 035]and hospitalization time[( 19. 3 ± 3. 1)days vs. ( 17. 3 ± 2. 5)days,P = 0. 035]were sig-nificantly prolonged. Temporary nerve dysfunction(52. 5％ vs. 32. 6％,P = 0. 002)and in-hospital mortality( 17. 5％ vs. 8. 1％,P = 0. 037)were significantly increased. Conclusion Preoperative total bilirubin ≥ 17. 1 μmol/ L,cardiopulmonary bypass time > 3. 5 h,a large number of hemolysis,the input amount of 24 h allogeneic red blood cell > 2000 ml were the in-dependent risk factors for perioperative hyperbilirubinemia in Stanford type A aortic dissection. The perioperative complications in≥51. 3 μmol/ L group were significantly increased. Therefore,more attention should be paid to the independent risk factors for perioperative hyperbilirubinemia in Stanford type A aortic dissection,hyperbilirubinemia and its clearance should be moni-tored more actively and dynamically,the cause should be found more precisely,the treatment be more comprehensive to achieve to control the level of bilirubinemia and improve the prognosis.