Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Streptococcus parasuis(S.parasuis)is a close relative of S.suis and can cause meningi-tis,pneumonia or systemic symptoms in affected animals.In this paper,the dominant strain was i-solated from diseased pigs with pneumonia in Jilin,China,and the isolated strain was identified as S.parasuis by 16S rRNA,it was named WYF-8B.Resistance was tested by the susceptibility tablet diffusion method,and WYF-8B was resistant to bacitracin,sulfamethoxoprim,lincomycin,erythro-mycin,fosfamycin,azithromycin,penicillin,doxycycline,cotrimotrixazole,sulfamisoxazole,cipro-floxacin,enrofloxacin,tetracycline,benzoxacillin,gentamicin,efazolin,and ampicillin.It was highly sensitive to florfenicol,chloramphenicol.Iochemical identification revealed that WYF-8B could fer-ment salicylic acid,maltose,lactose,sucrose,oxaesin,and glucose;nonfermentable mannitol,urea,raffinose,xylose,arabinose,and sorbitol.Using the second-generation whole-genome sequencing technology to study the WYF-8B resistant genotype,it was found that it carried the macrolide anti-biotic resistance genes Mef(E)and ErmB;resistance genes pbp2b,pbp1a,and pbp2x to β-lactam antibiotics;resistance genes gyrA,parC,and grlB to fluoroquinolones;resistance genes ANT(6)-Ia,AAC(6')-Ie-APH(2')-Ia,ANT(9)-Ia,APH(3')-Ⅲa to aminoglycoside antibiotics;re-sistance groups lnuB,lmrC,lmrD against lincomide antibiotics;resistance gene tetM to tetracy-cline antibiotics;the resistance gene of bacitracin,bcrA.The results found that the resistance phe-notype matches the resistance genotype of the sequencing results.The study of WYF-8B virulence factors found that WYF-8B carried 13 virulence factors(pavA,fbp 54,clpP,cps 4,cps 4 I,wbtB,cps,sI,tufA,galE,hasC,groEL,wrbtL,wbbtF),which mainly acted to promote bacterial diffu-sion,transfer,settlement,antiphagocytosis and immune evasion.The results of drug sensitivity test provide a reference for the study of clinical medication of S.parasuis,and drug resistance pheno-type and virulence factors lay the foundation for the research and development of new drugs and vaccines.

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 evaluate the clinical value of CD4 + T lymphocyte subsets such as helper Th2 in patients with recurrent uveitis (BU) in Beh?et′s disease (BD). Methods:The clinical data of 153 hospitalized patients diagnosed with Beh?et′s disease from January 1, 2020 to June 30, 2023 in the Second Hospital of Shanxi Medical University were retrospectively analyzed. The subsets of CD4 + T lymphocytes were measured, including helper T cells (Th cells) such as Th1, Th2, Th17 and regulatory T cells (Treg cells), biochemical lipid indexes (TC, TG, etc.), the frequency of oral ulcers in the past 1 year, the frequency of genital ulcers in the past 1 year, and drug use before admission;According to whether there was ocular involvement and uveitis, 153 cases of BD were divided into Beh?et non-uveitis group (non-BU group) and Beh?et uveitis group (BU group). The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group;The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group. The levels of cytokines and ICBD total score, the correlation between ICBD total score and various cytokines, and the diagnostic performance of Th2 cells were compared between BU group and non-BU group.The statistical methods were Mann-Whitney U test, independent sample t test, Chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis. Results:①The levels of Th1, Th2, Th17 cells, TC and TG in BU group were higher than those in non-BU group [133.87 (93.38, 229.87)/μl vs. 102.51(64.25, 149.23)/μl] and [9.43 (5.84, 14.13)/μl vs. 6.78(4.23, 9.44)/μl], [15.53 (9.36, 25.27)/μl vs. 9.83(5.46, 14.76)/μl], [4.21 (3.89, 4.90) mmol/L vs. 3.89(3.37, 4.34)mmol/L)], [1.43(1.00, 2.21)mmol/L vs. 0.96(0.69, 1.38)mmol/L], The differences were statistically significant ( Z=-3.24, Z=-3.05, Z=-3.94, Z=-2.25, Z=-3.47; all P<0.05); There was no statistical significance in Chi-square test between the two groups ( χ2=5.69, P>0.05).②The levels of IL-2, IL-10 and total ICBD score in BU group were higher than those in non-BU group, with statistical significance ( Z=-2.12, Z=-2.29, t=-6.48; all P<0.05). ③ The results of multiple logistic regression analysis showed that Th2 was an independent correlation factor for BU [ OR value (95% CI) was 1.143(1.007, 1.298), P=0.039]. The total score of BU patients was correlated with Th2 and Th17 cells. ROC analysis showed that the sensitivity of Th2 in diagnosing BU was 68.8%, the specificity was 49.5% and the area under the curve (95% CI) was 0.697 (0.585, 0.809) (P=0.001). Conclusion:CD4 + T lymphocyte subsets such as the absolute number of Th2 cells are related to BU, which is an important indicator to observe the severity of disease progression in BU patients, and has certain clinical value in evaluating the recurrence of BU in BD patients.

Objective To establish a method for simultaneous determination of 11 components of Solanum nigrum from different producing areas,and to evaluate the quality by chemometrics and entropy weight-technique for order preference by similarity to ideal solution(EW-TOPSIS).Methods The 17 batches of Solanum nigrum samples from 8 provinces were collected.The high performance liquid chromatography(HPLC)method was used to simultaneously determine the contents of medioresino,pinoresinol,quercetin,rutoside,solasonine,solamargine,khasianine,solasodine,desgalactotigonin,diosgenin and β-sitosterol,and the multi-components quantitative control mode of Solanum nigrum was established.The quality evaluation model of Solanum nigrum was established by using chemical recognition pattern and EW-TOPSIS method,and the overall quality was evaluated comprehensively.Results When the 11 components were in the 0.78-39.00,0.55-27.50,0.34-17.00,0.21-10.50,41.87-2 093.50,60.95-3 047.50,2.58-129.00,1.02-51.00,0.46-23.00,1.05-52.50 and 0.42-21.00 μg/mL(r＞0.999 0),their linear relationships were good.The average recovery was 96.81％-100.28％with the RSD＜2.0％(n=9).17 batches of samples clustered into 3 categories.Solamargine,solasonine,desgalactotigonin and medioresino may be the main potential markers affecting the quality of Solanum nigrum.The results of EW-TOPSIS method showed that,the quality evaluation closeness of 17 batches of Solanum nigrum were 0.433 6,0.416 8,0.624 2,0.500 8,0.479 1,0.636 1,0.568 3,0.250 0,0.190 9,0.222 1,0.170 7,0.720 0,0.698 3,0.744 7,0.717 9,0.720 9 and 0.718 3,respectively,indicating that the overall quality of Solanum nigrum from Liaoning,Jilin and Heilongjiang were better,followed by Jiangsu,Henan and Anhui.Conclusion The established HPLC method for simultaneous determination of 11 components in Solanum nigrum is convenient and accurate.Chemometrics and EW-TOPSIS method are objective and comprehensive,which can be used for the overall quality evaluation of Solanum nigrum.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies