Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Background There is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. Objective To explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. Methods The recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹. GDM was confirmed by oral glucose tolerance test (OGTT) between 24-28 weeks of gestation. A binary logistic regression model was applied to explore the association between SSB consumption and risk of GDM. Multiple linear regression was applied to investigate the associations between SSB consumption (per 1-serving·d⁻¹ increase) and OGTT fasting plasma glucose, 1-hour glucose, and 2-hour glucose. Results A total of 3811 pregnant women were finally enrolled in this study, of which 752 developed GDM, with an incidence rate of 19.7%. The incidence rates of GDM in pregnant women with SSB consumption frequency of <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹ were 18.0%, 21.1%, and 26.8%, respectively. After adjusting for maternal age, pre-pregnancy body mass index (BMI), education, number of children born, family history of diabetes, smoking, alcohol consumption, physical activity level, and total energy intake, the risk of GDM increased by 26% (OR=1.26, 95%CI: 1.05, 1.50) in the 1-4 servings·week⁻¹ group and by 76% (OR=1.76, 95%CI: 1.31, 2.38) in the ≥5 servings·week⁻¹ group compared to the <1 serving·week⁻¹ SSB consumption group, respectively. Further stratified analysis revealed no interaction effect (P_interaction>0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L⁻¹ and 0.18 mmol·L⁻¹, respectively (P<0.05), and no significant increase in fasting plasma glucose was found (P>0.05). Conclusion Higher SSB consumption before pregnancy increases the risk of GDM in pregnant women.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

The incidence of acute kidney injury (AKI) in Neonatal Intensive Care Unit (NICU) is about 30%.The morbidity and mortality of AKI are higher in very premature infants, very low birth weight infants and infants with long mechanical ventilation.Serum creatinine (Scr) and urine output are diagnostic indicators for AKI, which usually change within 12-48 hours after the onset of irreversible injury, and cannot be used for early diagnosis and clinical intervention.Therefore, it is necessary to search for indicators of early renal insufficiency, aiming to intervene and prevent early-stage AKI or reduce the occurrence of AKI.Near-infrared spectroscopy (NIRS) is a non-invasive, continuous, real-time monitoring method, which serves as a supplement to conventional biochemical markers.It provides evidence of early-stage renal ischemia and hypoxia, which contributes to prevent or reduce AKI.This study reviews the clinical application of neonatal renal oxygen saturation monitoring, thus providing clinical reference for renal function protection in critically ill neonates to reduce the occurrence of AKI and improve their prognosis.

Objective:To examine the difference of long-term recurrence rate and survivals between the young patients and the old patients undergoing breast conserving therapy (BCT).Methods:Women with primary invasive breast cancer receiving BCT between December 1999 and December 2014 were selected retrospectively from the database of Breast Cancer Center, Peking University Cancer Hospital & Institute. The median age of all patients was 47 years (range: 21 to 91 years). The cases were categorized according to age at diagnosis into two subgroups: the ≤40 years group and the>40 years group. A total of 2 778 patients were included: 677 patients in the ≤40 years group and 2 101 patients in the >40 years group. Clinicopathological characteristics between two groups were compared. The recurrence rate and survival were calculated using the Kaplan-Meier method. The differences of outcomes were compared in different aged groups using the Log-rank test. Factors affecting local recurrence, distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) were assessed by multivariable Cox proportional hazard models.Results:Proportions of T1 (301/677 vs. 1 160/2 101, χ2=37.660, P<0.01), involved lymph node (314/677 vs. 713/2 101, χ2=34.966, P<0.01) hormone receptor-negative (490/677 vs. 1 581/2 101, χ2=6.981, P=0.030) and neoadjuvant chemotherapy (413/677 vs. 1 010/2 101, χ 2=34.272, P<0.01)in the ≤40 years group were higher than that in the>40 years group. Median follow-up duration was 102 months. No significant difference in 10-year local recurrence was found between the two groups (2.5% vs. 1.6%, P=0.147). Ten-year DDFS rate in the ≤40 years group and in the>40 years group was 90.6% and 95.3%, respectively ( P<0.01). Ten-year DFS rate in the ≤40 years group and in the>40 years group was 86.5% and 91.1%, respectively ( P=0.001). Ten-year BCSS rate in the ≤40 years group and in the >40 years group was 91.0% and 93.7%, respectively ( P=0.105). Age was not the prognosis factor of local recurrence. Lymph node status (positive vs. negative: HR=2.73, 95%CI: 1.94 to 3.84, P<0.01), age (≤40 years vs.>40 years: HR=1.73, 95%CI: 1.24 to 2.42, P=0.001) and T stage (>2 cm vs. ≤2 cm: HR=1.61, 95%CI: 1.14 to 2.28, P=0.001) were the prognosis factors of DDFS, and also for DFS. Hormone receptor status (positive vs. negative: HR=0.54, 95%CI: 0.39 to 0.74, P<0.01), lymph node status (positive vs. negative: HR=2.94, 95%CI: 2.12 to 4.07, P<0.01) and T stage (>2 cm vs. ≤2 cm: HR=1.45, 95%CI: 1.05 to 2.01, P=0.025) were the prognosis factors of BCSS. Conclusions:The risk of local recurrence was similar between ≤40 years patient and >40 years patients receiving breast conserving therapy. Worse survivals in the ≤40 years group were found comparing to those in the >40 years group.

Objective:To examine the difference of long-term recurrence rate and survivals between the young patients and the old patients undergoing breast conserving therapy (BCT).Methods:Women with primary invasive breast cancer receiving BCT between December 1999 and December 2014 were selected retrospectively from the database of Breast Cancer Center, Peking University Cancer Hospital & Institute. The median age of all patients was 47 years (range: 21 to 91 years). The cases were categorized according to age at diagnosis into two subgroups: the ≤40 years group and the>40 years group. A total of 2 778 patients were included: 677 patients in the ≤40 years group and 2 101 patients in the >40 years group. Clinicopathological characteristics between two groups were compared. The recurrence rate and survival were calculated using the Kaplan-Meier method. The differences of outcomes were compared in different aged groups using the Log-rank test. Factors affecting local recurrence, distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) were assessed by multivariable Cox proportional hazard models.Results:Proportions of T1 (301/677 vs. 1 160/2 101, χ2=37.660, P<0.01), involved lymph node (314/677 vs. 713/2 101, χ2=34.966, P<0.01) hormone receptor-negative (490/677 vs. 1 581/2 101, χ2=6.981, P=0.030) and neoadjuvant chemotherapy (413/677 vs. 1 010/2 101, χ 2=34.272, P<0.01)in the ≤40 years group were higher than that in the>40 years group. Median follow-up duration was 102 months. No significant difference in 10-year local recurrence was found between the two groups (2.5% vs. 1.6%, P=0.147). Ten-year DDFS rate in the ≤40 years group and in the>40 years group was 90.6% and 95.3%, respectively ( P<0.01). Ten-year DFS rate in the ≤40 years group and in the>40 years group was 86.5% and 91.1%, respectively ( P=0.001). Ten-year BCSS rate in the ≤40 years group and in the >40 years group was 91.0% and 93.7%, respectively ( P=0.105). Age was not the prognosis factor of local recurrence. Lymph node status (positive vs. negative: HR=2.73, 95%CI: 1.94 to 3.84, P<0.01), age (≤40 years vs.>40 years: HR=1.73, 95%CI: 1.24 to 2.42, P=0.001) and T stage (>2 cm vs. ≤2 cm: HR=1.61, 95%CI: 1.14 to 2.28, P=0.001) were the prognosis factors of DDFS, and also for DFS. Hormone receptor status (positive vs. negative: HR=0.54, 95%CI: 0.39 to 0.74, P<0.01), lymph node status (positive vs. negative: HR=2.94, 95%CI: 2.12 to 4.07, P<0.01) and T stage (>2 cm vs. ≤2 cm: HR=1.45, 95%CI: 1.05 to 2.01, P=0.025) were the prognosis factors of BCSS. Conclusions:The risk of local recurrence was similar between ≤40 years patient and >40 years patients receiving breast conserving therapy. Worse survivals in the ≤40 years group were found comparing to those in the >40 years group.

Objective: To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy. Methods: The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis. Results: There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m². (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m^2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m^2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m^2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ²=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D₁ lymph lode dissection, D₂ lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ²=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ²=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05). Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.

Objective:To analyze the safety and short-term efficacy of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer.Methods:A total of 101 consecutive patients who received breast-conserving surgery plus intraoperative radiotherapy were recruited to summarize the recent follow-up results and clinicopathological data. Univariate analysis and Logistic regression model were used to evaluate the factors affecting the postoperative adverse reactions and cosmetic effects.Results:Among 101 patients, 4 patients had recurrence or metastasis. The 3-years disease free survival rate was 94.9%, and the 3-years cumulative recurrence rate was 5.1%. Univariate analysis showed that the menstrual status and postoperative whole breast radiotherapy were associated with the postoperative adverse reactions ( P<0.05). The T stage and applicator diameter were associated with the cosmetic effect ( P<0.05). Multivariate analysis indicated that the diameter of the applicator ( OR=3.701, P=0.026) and postoperative whole breast radiotherapy ( OR=5.962, P=0.005) were independent factors for the postoperative adverse reactions, and the diameter of the applicator ( OR=2.522, P=0.037) was an independent factor for the cosmetic effect. Conclusion:Breast-conserving surgery combined with intraoperative radiotherapy shows safety and good short-term efficacy in low-risk early-stage breast cancer.

Objective:To analyze the safety and short-term efficacy of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer.Methods:A total of 101 consecutive patients who received breast-conserving surgery plus intraoperative radiotherapy were recruited to summarize the recent follow-up results and clinicopathological data. Univariate analysis and Logistic regression model were used to evaluate the factors affecting the postoperative adverse reactions and cosmetic effects.Results:Among 101 patients, 4 patients had recurrence or metastasis. The 3-years disease free survival rate was 94.9%, and the 3-years cumulative recurrence rate was 5.1%. Univariate analysis showed that the menstrual status and postoperative whole breast radiotherapy were associated with the postoperative adverse reactions ( P<0.05). The T stage and applicator diameter were associated with the cosmetic effect ( P<0.05). Multivariate analysis indicated that the diameter of the applicator ( OR=3.701, P=0.026) and postoperative whole breast radiotherapy ( OR=5.962, P=0.005) were independent factors for the postoperative adverse reactions, and the diameter of the applicator ( OR=2.522, P=0.037) was an independent factor for the cosmetic effect. Conclusion:Breast-conserving surgery combined with intraoperative radiotherapy shows safety and good short-term efficacy in low-risk early-stage breast cancer.