Objective:To compare the outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of tumors in isolated kidney, and analyze the factors influencing postoperative renal function and long-term survival in patients.Methods:A retrospective analysis was conducted on clinical data of 67 patients with tumors in isolated kidney who underwent surgery at the Chinese PLA General Hospital from November 2010 to January 2022. There were 48 males and 19 females, with an average age of (58.6±10.1) years old. The patients were divided into RAPN group (43 cases) and LPN group (24 cases) based on the surgical approach. The RAPN group had a higher R.E.N.A.L. score than the LPN group [(8.7±1.5) vs. (7.9±1.7), P=0.042]. There were no statistically significant differences between the two groups in terms of age [(57.4±10.2) years old vs. (60.9±9.8) years old, P=0.185], body mass index (BMI) [(25.7±3.5) kg/m 2 vs. (25.1±3.6) kg/m 2, P=0.518], and preoperative serum creatinine [(102.9±31.6) μmol/L vs. (102.3±22.4) μmol/L, P=0.930]. Twelve cases underwent hypothermic treatment during surgery, with 9 cases(20.9%) in the RAPN group and 3 cases(12.5%) in the LPN group( P=0.596). Surgical time, intraoperative warm ischemia time, intraoperative blood loss, postoperative fasting time, perioperative complication rate, postoperative serum creatinine, and other indicators were compared between the two groups. Multiple linear regression analysis was used to identify factors affecting postoperative serum creatinine. Kaplan-Meier curves were employed to analyze patient prognosis, and log-rank tests were performed to compare the differences between the two groups. Multiple Cox regression analysis was used to identify factors influencing patient prognosis. Results:All surgeries were completed successfully with negative pathological margins. There were no statistically significant differences between the RAPN and LPN groups in terms of surgical time [(136.6±47.6) min vs. (125.3±34.4) min, P=0.311], intraoperative ischemia time [23.0 (16.0, 30.0) min vs. 19.0 (13.5, 27.5) min, P =0.260], intraoperative blood loss [50.0 (50.0, 100.0) ml vs. 50.0 (22.5, 100.0) ml, P=0.247], postoperative hospital stay [(6.6±3.5) days vs. (7.7±4.2) days, P=0.244], time to drain removal [4(3, 5) days vs. 5(3, 6) days, P =0.175], postoperative fasting time [(2.1±0.7) days vs. (2.2±1.0) days, P=0.729], perioperative complication rate [18.6% (8/43) vs. 16.7% (4/24), P=1.000], postoperative serum creatinine [145.2 (128.3, 191.3) μmol/L vs. 157.8 (136.2, 196.3) μmol/L, P =0.229], and pathological staging [T 1a/T 1b/T 2a/T 3a/T 4 stage: 32/7/1/3/0 case vs. 17/5/0/1/1 case, P=0.804]. Kaplan-Meier survival curves showed that the total survival rates at 1, 3, and 5 years after surgery were 94.7%, 84.9%, and 84.9% for the RAPN group, and 100.0%, 95.5%, and 95.5% for the LPN group, with no statistically significant difference in the log-rank test ( P=0.116). Excluding 10 patients with preoperative tumor metastasis (7 in the RAPN group and 3 in the LPN group), the progression-free survival rates at 1, 3, and 5 years after surgery were 84.8%, 81.1%, and 81.1% for the RAPN group, and 100.0%, 95.0%, and 90.0% for the LPN group, with no statistically significant difference in the log-rank test ( P =0.142). Multiple linear regression analysis showed that the use of hypothermic treatment during surgery significantly reduced postoperative serum creatinine ( B=-72.191, P=0.048). Multiple Cox regression analysis revealed that BMI ( HR=0.743, P=0.044), pathological T stage ( HR=4.235, P=0.018), and preoperative metastasis ( HR=18.829, P=0.035) were independent factors affecting patient overall survival time. A smaller BMI, higher pathological stage, and preoperative metastasis were associated with poorer prognosis. Conclusions:Despite the higher R. E.N.A.L. score and greater surgical difficulty in the RAPN group, RAPN achieved similar perioperative and prognostic results as the LPN, indicating RAPN advantages in treating tumors in isolated kidney. Appropriate intraoperative hypothermic treatment can better protect postoperative renal function. BMI, pathological T stage, and preoperative metastasis are independent factors affecting overall survival time.

The CRISPR/Cas is an immune defense system acquired by prokaryotes to resist the invasion of foreign genetic materials during their evolutionary process.In recent years,it has been developed into an efficient tool for genome editing,gene regulation and molecular diagnosis.Its programmable targeting mechanism has opened the door to use this system for genome manipulation and allows for dynamic regu-lation and control of gene expression within its activity range.As one of the most flexible and cost-effec-tive techniques among existing gene modification methods,it has been widely applied in clinical disease treatment,industrial and agricultural production,sustainable dye development,chemical processing and many other fields.With the continuous investigation and exploration of the CRISPR/Cas system,a large number of studies have been reported on the engineering modification and optimization approaches of gRNA,including changing the length of the spacer region,regulating the structure of constant and varia-ble sequence parts,adding extra functional sequences through the end or middle extension,and chemical synthesis modifications,in order to reduce off-target and mutation rates,improve the efficiency of the CRISPR system,and fully stimulate the potential of CRISPR gene manipulation tools in biomedical fields.Based on this,this review will introduce the latest progress in gRNA engineering design strategies and application research of CRISPR/Cas9 and CRISPR/Cas12 systems,analyze and discuss the opportu-nities and challenges in the current gRNA engineering technology,aiming to provide ideas and reference directions for obtaining gRNAs with better performance,thereby effectively improving the ability to probe the human genomes using the CRISPR/Cas system and bringing more possibilities to programmable biology.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To analyze the clinical efficacy and safety of glecaprevir/pibrentasvir in the treatment of pa-tients with hepatitis C virus(HCV)and human immunodeficiency virus(HIV)co-infection,and provide scientific basis for clinical treatment.Methods 89 initially treated non-cirrhotic patients with HCV/HIV co-infection in a hospital of Butuo County of Liangshan Prefecture from January 2021 to January 2022 were selected.All patients re-ceived glecaprevir/pibrentasvir treatment for 8 weeks and were followed up for 12 weeks.Virological response rate at the end-of-treatment and sustained virological response rate after 12 weeks(SVR12)of treatment as well as oc-currence of adverse reaction were recorded.Results Among 89 initially treated non-cirrhotic patients with HCV/HIV co-infection,most were middle-aged and young married men(n=79,88.8％).HIV was mainly transmitted through sexual contact(n=62,69.7％)and intravenous drug use(n=27,30.3％).The most common HCV geno-types were genotype 1b(n=33,37.1％)and genotype 3b(n=25,28.1％).All patients completed 8 weeks of treatment successfully and HCV RNA load at the end of treatment was below the detection limit(＜25 IU/mL).Eight patients failed to complete the follow-up,and the remaining 81(100％)patients achieved a sustained virologic re-sponse.There were no serious adverse reactions during the observation period,but 11 patients had mild adverse re-actions.Conclusion The 8-week treatment regimen of glecaprevir/pibrentasvir for non-cirrhotic patients with geno-type 1,3,and 6 HCV/HIV co-infection can achieve 100％SVR12,with high safety and tolerability,which can be used as a good choice for clinical treatment of these patients.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

ObjectiveTo observe the effect of Shenling Baizhusan on the intestinal inflammatory reaction in the rat model of Crohn's disease （CD） and study its relationship with p38 mitogen-activated protein kinase （MAPK） signaling pathway， so as to provide an experimental and theoretical basis for the clinical application of this prescription. MethodA total of 72 SD rats （36 males and 36 females） were randomized into a normal group （n=12） and a modeling group （n=60）. The rats in the modeling group were treated with 2，4，6-trinitrobenzene sulfonic acid （TNBS， 3 mL·kg^-1） and then randomized into model， mesalazine （0.21 g·kg^-1·d^-1）， and low-， medium-， and high-dose （5.88， 11.76， 23.59 g·kg^-1·d^-1， respectively） Shenling Baizhusan groups. The rats in the drug intervention groups were administrated with corresponding agents by gavage for 14 days， and those in the normal and model groups with an equal volume of distilled water. The disease activity index （DAI） score of inflammatory bowel disease （IBD） and the colon mucosal damage index （CMDI） score of rats in each group were assessed after gavage. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the colon， and enzyme-linked immunosorbent assay （ELISA） to measure the levels of tumor necrosis factor alpha （TNF-α）， interleukin-1 （IL-1）， and interleukin-6 （IL-6） in the serum. Western blotting was employed to determine the protein levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， p65 nuclear factor （NF）-κB， and phosphorylated-p65 NF-κB （p-NF-κB p65） in the colon tissue. Quantitative real-time polymerase chain reaction was conducted to determine the miRNA levels of p38 MAPK and NF-κB p65 in the colon tissue. ResultThe model group had higher DAI and CMDI scores than the normal group （P<0.01） and showed damaged epithelial cells in the colon mucosa， disarrangement of glands， damaged simple tubular glands， local necrosis， infiltration of a large number of inflammatory cells and lymphocytes in each layer， and presence of ulceration. Compared with the normal group， the model group showed elevated levels of TNF-α， IL-1， and IL-6 in the serum （P<0.01） and up-regulated protein levels of p-p38 MAPK and p-NF-κB p65 and miRNA level of p38 MAPK in the colon tissue （P<0.01）. Compared with the model group， mesalazine and high- and medium-dose Shenling Baizhusan decreased the DAI and CMDI scores （P<0.05， P<0.01）， repaired the mucosal epithelium of the colon tissue， increased the glands and goblet cells， lowered the levels of TNF-α， IL-1， and IL-6 in the serum （P<0.05， P<0.01）， and down-regulated the protein levels of p-p38 MAPK and p-NF-κB p65 and the miRNA level of p38 MAP in the colon mucosa （P<0.01， P<0.05）. ConclusionShenling Baizhusan can reduce intestinal inflammation of CD rats and promote the repair of colon mucosa by down-regulating the protein levels of p-p38 MAPK and pNF-κB p65 and the miRNA level of p38 MAPK to inhibit the p38 MAPK pathway.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs). METHODS: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery. RESULTS: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred. CONCLUSION For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.
Humans ; Tarlov Cysts/epidemiology* ; Retrospective Studies ; Neoplasm Recurrence, Local/complications* ; Cysts/surgery* ; Pain