[Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns].

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Protective Effects of Aspirin Supplemented With Quercetin in L-NAME-Induced Preeclampsia-Like Rats.

Aspirin supplemented with quercetin was reported to enhance the therapeutic effects of aspirin in a rat model of preeclampsia. In this study, the underlying mechanisms were further explored. Preeclampsia was induced by L-NAME (50 mg/kg/day) via oral gavage from gestation day (GD)14 to GD19. Aspirin (1.5 mg/kg/day) administration was performed using aspirin mixed with rodent dough from GD0 to GD19. The administration of quercetin (2 mg/kg/day) was performed by intraperitoneal infusion from GD0 to GD19. Protein levels were evaluated using ELISA or Western blot, and microRNA (miRNA) level was evaluated by RT-PCR. Aspirin supplemented with quercetin ameliorated the increase of systolic blood pressure (SBP), proteinuria, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and improved the pregnancy outcomes in preeclampsia rats. Aspirin supplemented with quercetin inhibited miR-155 expression in preeclampsia rats. The decreased miR-155 level in placenta further increased the protein level of SOCS1 and inhibited the phosphorylation of p65. In this study, we demonstrated that aspirin supplemented with quercetin enhanced the effects of aspirin for the treatment of preeclampsia.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Etiological diagnostic methods and research progress of forest encephalitis].

Forest encephalitis is a natural focal disease transmitted through the bite of hard ticks, and its pathogen is the tick-borne encephalitis virus from the Flaviviridae family. The mortality rate of forest encephalitis is relatively high, making laboratory testing significant in diagnosing this disease. This article elaborates on the etiological diagnostic methods and recent research progress in forest encephalitis. Laboratory tests for forest encephalitis mainly include routine examinations, serological tests, virus isolation, and molecular biological testing. The detection of serum-specific IgM antibodies against the forest encephalitis virus is of great importance for early diagnosis, and specific IgG antibodies serve as a "gold standard" for differentiation from other diseases. Techniques such as enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay for detecting specific IgM antibodies in serum and/or cerebrospinal fluid, the serum hemagglutination inhibition test or serum complement fixation test, and the double serum hemagglutination inhibition test or complement fixation test all contribute to the early diagnosis. The development of molecular testing methods is rapid, and techniques such as metabolomics, digital PCR, and matrix metalloproteinases are also applied in the early diagnosis of forest encephalitis.

[Observation on the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation for the treatment of tremor-dominant subtypes of Parkinson's disease].

Objective: To analyze the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of tremor Parkinson's disease(PD). Method: A total of 82 patients with primary PD who were admitted to the Department of Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 1, 2020 to March 31, 2021 were prospectively collected. According to the clinical characteristics of major movement disorders, 82 patients with tremor type (TD) were selected to enroll.The patients were randomly divided into 3 groups at a 1∶1∶1 ratio according to the randomized coding sequence of the trial: the primary motor cortex (M1) group with 26 cases, the cerebellum group with 26 cases and the dual-site (M1, cerebellum) group with 30 cases. All patients were treated with 1 Hz low-frequency stimulation of the corresponding target once a day for 5 days a week for 2 weeks, a total of 10 times; The dosage remained unchanged during the treatment for all groups. Before and after 2 weeks' treatment, the patients were assessed with the Unified PD Rating Scale (UPDRS) and PD Quality of Life Questionnaire-39 (PDQ-39) without medication. Cortical excitability, namely transcranial magnetic stimulation motor evoked potential (TMS-MEP), [including resting motor threshold (rMT) and active motor threshold (aMT) examinations], timed up and go (TUG) and electromyographic tremor were conducted. Result: There were 82 patients, 39 males and 43 females, with an average age of (67±8) years. Before the treatment, there was no statistically significant difference in the evaluation indicators among the three groups (all P>0.05). After the treatment, the differences of the UPDRS-Ⅲ score [(38.9±2.5) vs (29.2±3.6) ], UPDRS tremor score [(23.7±2.1) vs (14.6±3.1) ], TUG time [(44.8±3.1) s vs (33.7±4.1) s], tremor amplitude [(480±126) µV vs (276±94) µV], PDQ-39 score [(51±13) vs (45±13) ], rMT [(36±17)% vs (43±13)%], and aMT [(26±16)% vs (31±12)%] were statistically significant (all P<0.01) from those before the treatment. There was no statistical difference in the above factors between the M1 group and cerebellum group (all P>0.05). There was no statistically significant difference in tremor peak frequency among the three groups before and after the treatment (all P>0.05). Conclusions: Dual-site low-frequency rTMS can improve PD tremor, while M1 or cerebellar low-frequency rTMS does not significantly improve PD tremor. Its mechanism may be to improve PD tremor symptoms by regulating cortical excitability.

[Effect of PCSK9 inhibitors on early neurological deterioration in patients with branch atheromatous disease].

Objective: To investigate the effect of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors on the incidence of early neurological deterioration during the treatment of branch atheromatous disease (BAD). Methods: A retrospective analysis of 297 BAD patients admitted to the Department of Neurology in Zhengzhou People's Hospital from January 2020 to April 2023 was made. According to whether to use PCSK9 inhibitor treatment, they were divided into PCSK9 inhibitor group (81 cases) and control group (216 cases). Propensity score matching (PSM) method was used to eliminate the general situation difference between PCSK9 inhibitor group and control group. Seventy-two cases were successfully matched in each group. The early neurological deterioration (END) and low-density lipoprotein cholesterol (LDL-C) were compared. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase≥2 points within 72 hours after stroke. Suspicious influencing factors leading to END were screened for multivariate logistic regression model analysis. Results: After PSM matching, among the 144 patients, 90 were male and 54 were female, aged (61.2±9.6) years. After matching, The hospital stay[M(Q1, Q3)] [9(7, 11)d vs 10(8, 13)d] in PCSK9 and NIHSS score at discharge [2(1, 3) vs 3(1, 4) points] were significantly different from those in the control group (all P<0.05). In addition, the incidence of END was reduced in the PCSK9 inhibitor group [12.5%(9/72) vs 31.9%(23/72),P<0.05]. Multivariate logistic regression analysis found that C-reactive protein (CRP)(OR=1.119,95%CI: 1.010-1.240, P<0.05) and PCSK9 inhibitor (OR=0.298, 95%CI: 0.117-0.755, P<0.05) were factors associated with the development of END. Conclusion: The use of PCSK9 inhibitors in the treatment of patients with BAD can reduce the incidence of END.

Disentangling the roles of chance, abiotic factors and biotic interactions among epiphytic bryophyte communities in a tropical rainforest (Yunnan, China).

Epiphytes offer an appealing framework to disentangle the contributions of chance, biotic and abiotic drivers of species distributions. In the context of the stress-gradient theory, we test the hypotheses that (i) deterministic (i.e., non-random) factors play an increasing role in communities from young to old trees, (ii) negative biotic interactions increase on older trees and towards the tree base, and (iii) positive interactions show the reverse pattern. Bryophyte species distributions and abiotic conditions were recorded on a 1.1 ha tropical rainforest canopy crane site. We analysed co-occurrence patterns in a niche modelling framework to disentangle the roles of chance, abiotic factors and putative biotic interactions among species pairs. 76% of species pairs resulted from chance. Abiotic factors explained 78% of non-randomly associated species pairs, and co-occurrences prevailed over non-coincidences in the remaining species pairs. Positive and negative interactions mostly involved species pairs from the same versus different communities (mosses versus liverworts) and life forms, respectively. There was an increase in randomly associated pairs from large to small trees. No increase in negative interactions from young to old trees or from the canopy to the base was observed. Our results suggest that epiphytic bryophyte community composition is primarily driven by environmental filtering, whose importance increases with niche complexity and diversity. Biotic interactions play a secondary role, with a very marginal contribution of competitive exclusion. Biotic interactions vary among communities (mosses versus liverworts) and life forms, facilitation prevailing among species from the same community and life form, and competition among species from different communities and life forms.

[Perspectives on molecular diagnosis and targeted therapy for complex vascular malformations in pediatrics].

Vascular malformations are due to abnormal development of blood and/or lymphatic vessels during embryonic life without endothelial cell proliferation. Most of the previous treatments were symptomatic methods as surgery and sclerotherapy because the pathogenic mechanism was not clearly understood. With advances in molecular biology, the pathogenesis of vascular malformations is thought to be related to inherited and/or somatic mutations that eventually activate the PI3K/ATK/mTOR, Ras/Raf/MEK/ERK pathways. Also, related studies have promoted the use of targeted inhibitors. This article provides a review of current causative genes and targeted drugs for pediatric vascular malformations, aiming to provide a basis for promoting accurate molecular diagnosis and precision targeted therapy for these diseases.

Deep learning for the early identification of periodontitis: a retrospective, multicentre study.

AIM: To develop a deep-learning model to help general dental practitioners diagnose periodontitis accurately and at an early stage. MATERIALS AND METHODS: First, the panoramic radiographs (PARs) from the Second Affiliated Hospital of Nanchang University were input into the convolutional neural network (CNN) architecture to establish the PAR-CNN model for healthy controls and periodontitis patients. Then, the PARs from the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were included in the second testing set to validate the effectiveness of the model with data from two centres. Heat maps were produced using a gradient-weighted class activation mapping method to visualise the regions of interest of the model. The accuracy and time required to read the PARs were compared between the model, periodontal experts, and general dental practitioners. Areas under the receiver operating characteristic curve (AUCs) were used to evaluate the performance of the model. RESULTS: The AUC of the PAR-CNN model was 0.843, and the AUC of the second test set was 0.793. The heat map showed that the regions of interest predicted by the model were periodontitis bone lesions. The accuracy of the model, periodontal experts, and general dental practitioners was 0.800, 0.813, and 0.693, respectively. The time required to read each PAR by periodontal experts (6.042 ± 1.148 seconds) and general dental practitioners (13.105 ± 3.153 seconds), which was significantly longer than the time required by the model (0.027 ± 0.002 seconds). CONCLUSION: The ability of the CNN model to diagnose periodontitis approached the level of periodontal experts. Deep-learning methods can assist general dental practitioners to diagnose periodontitis quickly and accurately.

[The value of dynamic contrast-enhanced MRI in the differentiation between benign and malignant lacrimal epithelial tumors].

Objective: To investigate the diagnostic performance of multiparametric dynamic contrast-enhanced MRI(DCE-MRI) for the differentiation between benign and malignant larcrimal gland epithelial tumors. Methods: The clinical and imaging data of 104 patients with epithelial tumors of the lacrimal gland who underwent orbital MRI scan and met the inclusion criteria in Beijing Tongren Hospital from January 2011 to December 2017 were retrospectively collected, including 48 males and 56 females, aged from 12 to 77 (43±7) years. Sixty-three cases of benign epithelial tumors and 41 cases of malignant epithelial tumors were examined by DCE-MRI. The parameters of semiquantitative analysis including: time to peak enhancement (Tpeak), maximum enhancement ratio (ERmax), Slope, washout ratio (WR) and time-signal intensity curve (TIC) types. The parameters of quantitative analysis including: volume transfer constant (Ktrans), the extravascular extracellular volume fraction (Ve) and rate constant (Kep). Receiver operating characteristic (ROC) curve analysis was performed for DCE-MRI parameters with statistically significant differences, the area under the curve (AUC) was calculated, the diagnostic threshold was determined, and the diagnostic performance was evaluated. Logistic regression analysis was used to determine the best parameters for differential diagnosis of benign and malignant epithelial tumors of the lacrimal gland. Results: For the semiquantitative analysis of DCE-MRI, malignant lacrimal gland epithelial tumor had a significantly shorter Tpeak than benign masses [(103.77±57.87) s vs (187.80±77.01) s,P<0.001)], while had a higher value in ERmax, Slope [M(Q1,Q3)] and WR in malignant masses compared with benign one [1.55±0.39 vs 1.36±0.33; 1.76 (0.97,2.27) vs 0.62 (0.50,0.93); 7.70%(1.40%, 21.60%)% vs 0(0, 0),all P<0.05)].The TICs of benign lacrimal tumors mainly showed a persistent type (49/63),while most malignant lacrimal tumors mainly showed a plateau type (25/41). For the quantitative analysis of DCE-MRI, the values of Ktrans and Kep[M(Q1,Q3)] in malignant tumors were significantly greater than those of benign tumors (0.99±0.52/min vs 0.43±0.23/min, P<0.001; 1.33(0.83, 1.55)/min vs 0.55(0.46, 0.68)/min, P<0.001). No significant difference in Ve was found between the groups (0.76±0.20 vs 0.73±0.22,P=0.467). Through the statistical analysis, TIC types (OR=3.887,95%CI: 1.409-10.725) and Ktrans(OR=50.979,95%CI: 6.046-429.830) can provide superior diagnostic performance for predicting malignant lacrimal gland epithelial tumors, with a sensitivity of 78.05%, specificity of 77.78%,and sensitivity of 70.73%, specificity of 95.24%, respevtively. Furthermore, the comprehensive diagnostic performance of Ktrans in AUC was proven to be significantly better than that of TIC [0.875 (0.796-0.932) vs 0.798 (0.708-0.870),P=0.049]. Conclusions: Multiparametric DCE-MRI is helpful for the differential diagnosis of benign and malignant epithelial tumors of lacrimal gland. TIC type and Ktrans have higher diagnostic value, and the diagnostic performance of Ktrans is better than that of TIC.

[Recommendations for diagnosis and treatment of systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

The value of microbiology rapid on-site evaluation of sepsis caused by pulmonary infection.

OBJECTIVE: This study aims to evaluate the value of microbial rapid on-site evaluation (M-ROSE) of sepsis, and septic shock caused by pulmonary infection. PATIENTS AND METHODS: Thirty-six patients with sepsis and septic shock due to hospital-acquired pneumonia were analyzed. Accuracy and time were compared with M-ROSE, traditional culture, and next-generation sequencing (NGS). RESULTS: A total of 48 strains of bacteria and 8 strains of fungi were detected by bronchoscopy in 36 patients. The accuracy rate of bacteria and fungi was 95.8% and 100%, respectively. M-ROSE took an average of 0.34±0.01 hours, much faster than NGS (22h±0.01 h, p<0.0001) and traditional culture time (67.50±0.91 h, p<0.0001). CONCLUSIONS: M-ROSE may quickly identify common bacteria and fungi, so it may be a useful method for the etiological diagnosis of sepsis and septic shock caused by pulmonary infection.

[Analysis on survival time and influencing factors among reported HIV/AIDS in Yunnan Province, 1989-2021].

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4+T lymphocytes counts (CD4) counts levels of 200-349 cells/µl, 350-500 cells/µl and ≥501 cells/µl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/µl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.

[Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients].

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Suvemcitug as second-line treatment of advanced or metastatic solid tumors and with FOLFIRI for pretreated metastatic colorectal cancer: phase Ia/Ib open label, dose-escalation trials.

BACKGROUND: Suvemcitug (BD0801), a novel humanized rabbit monoclonal antibody against vascular endothelial growth factor, has demonstrated promising antitumor activities in preclinical studies. PATIENTS AND METHODS: The phase Ia/b trials investigated the safety and tolerability and antitumor activities of suvemcitug for pretreated advanced solid tumors and in combination with FOLFIRI (leucovorin and fluorouracil plus irinotecan) in second-line treatment of metastatic colorectal cancer using a 3 + 3 dose-escalation design. Patients received escalating doses of suvemcitug (phase Ia: 2, 4, 5, 6, and 7.5 mg/kg; phase Ib: 1, 2, 3, 4, and 5 mg/kg plus FOLFIRI). The primary endpoint was safety and tolerability in both trials. RESULTS: All patients in the phase Ia trial had at least one adverse event (AE). Dose-limiting toxicities included grade 3 hyperbilirubinemia (one patient), hypertension and proteinuria (one patient), and proteinuria (one patient). The maximum tolerated dose was 5 mg/kg. The most common grade 3 and above AEs were proteinuria (9/25, 36%) and hypertension (8/25, 32%). Forty-eight patients (85.7%) in phase Ib had grade 3 and above AEs, including neutropenia (25/56, 44.6%), reduced leucocyte count (12/56, 21.4%), proteinuria (10/56, 17.9%), and elevated blood pressure (9/56, 16.1%). Only 1 patient in the phase Ia trial showed partial response, [objective response rate 4.0%, 95% confidence interval (CI) 0.1% to 20.4%] whereas 18/53 patients in the phase Ib trial exhibited partial response (objective response rate 34.0%, 95% CI 21.5% to 48.3%). The median progression-free survival was 7.2 months (95% CI 5.1-8.7 months). CONCLUSIONS: Suvemcitug has an acceptable toxicity profile and exhibits antitumor activities in pretreated patients with advanced solid tumors or metastatic colorectal cancer.