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In this study, 6229 brown rice grains from three major rice-producing regions were collected to investigate the spatial and variety distributions of heavy metals in rice grains in China. The potential sources of heavy metals in rice grains were identified using the Pearson correlation matrix and principal component analysis, and the health risks of dietary exposure to heavy metals via rice consumption were assessed using the hazard index (HI) and total carcinogenic risk (TCR) method, respectively. Moreover, 48 paired soil and rice samples from 11 cities were collected to construct a predicting model for Cd accumulation in rice grains using the multiple linear stepwise regression analysis. The results indicated that Cd and Ni were the main heavy metal pollutants in rice grains in China, with approximately 10% of samples exceeding their corresponding maximum allowable limits. The Yangtze River basin had heavier pollution of heavy metals than the Southeast Coastal Region and Northeast Plain, and the indica rice varieties had higher heavy metal accumulation abilities compared with the japonica rice. The Cu, Pb, and Cd mainly originated from anthropogenic sources, while As, Hg, Cr, and Ni originated from both natural and anthropogenic sources. The mean HI and TCR values of dietary exposure to heavy metals via rice consumption ranged from 2.92 to 4.31 and 9.74 × 10−3 to 1.44 × 10−2, respectively, much higher than the acceptable range, and As and Ni were the main contributor to the HI and TCR for Chinese adults and children, respectively. The available Si (ASi), total Cd (TCd), available Mo (AMo), and available S (AS) were the main soil factors determining grain Cd accumulation. A multiple linear stepwise regression model was constructed based on ASi, TCd, AMo, and AS in soils with good accuracy and precision, which could be applied to predict Cd accumulation in rice grains and guide safe rice production in contaminated paddy fields. [ABSTRACT FROM AUTHOR]

Purpose: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. Methods: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. Results: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. Conclusions: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib. [ABSTRACT FROM AUTHOR]

The rapid development of the Internet had a profound influence on the spatial distribution of economic output activities. On the basis of theoretical analysis, this study takes China's regions as research samples and construct a spatial econometric model to empirically analyze the impact of Internet development on regional productivity. The analysis reveals that the distribution of regional productivity in China had significant spatial correlation; regional productivity had positive spatial externalities; Internet development had significant promotion effects and positive spatial spillover effects to regional productivity, but the effects are heterogeneous in different subregions. The subregion analysis shows that the optimization effect of the Internet on regional productivity exhibits heterogeneity in different subregions. The threshold effect analysis reveals the increasing marginal effect of Internet development on regional productivity, and economic development and human capital supply are important factors restricting this marginal effect. Altogether, this study provides useful references on the positive effects of the Internet on regional productivity in the spatial dimension, and suggests that the policy makers can optimize the spatial distribution of regional productivity by promoting Internet access in various regions and narrowing the digital divide among regions. [ABSTRACT FROM AUTHOR]

Purpose: Human epidermal growth factor 2 (HER2) alterations are found in approximately 2%–5% of non-small cell lung cancer (NSCLC). This study aimed to evaluate the clinical characteristics of patients with NSCLC having HER2 alterations in China and the differences compared with Western counterparts and also perform a prognostic analysis. Material and Methods: A total of 1300 patients diagnosed with NSCLC from January 2017 to December 2020 were included. Their clinical characteristics were retrospectively recorded. The gene expression profiles and clinical information of 20 patients having altered HER2 were downloaded from the Cancer Genome Atlas database and compared, and the prognostic factors affecting the Chinese population were analyzed. If tissues were sufficient, the overexpression was assessed by immunohistochemical staining. Results: Among 39 (3.0%) patients with HER2 alterations, 31 patients (79.5%) had HER2 mutations. HER2 insertion mutation in exon 20 was the most common type (A775_G776 ins YVMA). Seven patients (17.9%) had amplification, and one had both. The HER2 kinase domain was most commonly mutated. A majority of patients in the study were young-aged with no smoking history; 66.7% had stage III/IV adenocarcinoma. Compared with Chinese patients, HER2 alterations in Western counterparts were mostly associated with old age, previous smoking, and stages I and II at diagnosis. The most common type of HER2 alteration was HER2 amplification; one patient had coexistence of HER2 gene amplification and fusion. The furin-like cysteine-rich region was most commonly mutated. The median overall survival (OS) of the Chinese patients was 41 months. The univariate analysis showed that age > 60 years, no surgical treatment, no liver or renal cysts on imaging, and maximum tumor diameter ≥ 4.25 cm were significantly associated with poor OS. The multivariate analysis showed that age, presence of surgery, and no hepatic or renal cysts were independent prognostic factors for OS. Chemotherapy achieved better outcomes, and HER2 mutations were not associated with HER2 amplification and overexpression. Conclusions: This study was novel in comprehensively investigating the clinical and molecular characteristics of patients in Chinese and Western populations, and in analyzing the factors affecting the prognosis of Chinese patients. It provided critical data for future therapies against HER2-altered NSCLC. [ABSTRACT FROM AUTHOR]

Isoetes orientalis is an endangered hexaploidy species of Isoetaceae in China and the complete chloroplast genome of this species has not been reported. In the present study, a complete chloroplast genome of Isoetes orientalis (Isoetaceae) was assembled and annotated. This chloroplast genome has a circular structure of 145,504 bp in length, comprising a pair of inverted repeat (IR) regions of 13,207 bp each, a large single-copy (LSC) region of 91,864 bp, and a small single-copy (SSC) region of 27,226 bp. The chloroplast genome contains 136 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that I. orientalis was closely related to I. sinensis. These results provide additional resources for future studies on Isoetes from China and across the globe. [ABSTRACT FROM AUTHOR]

The residual levels of 25 monitored pesticides in 6,229 brown rice samples obtained from the 17 provinces of the three main rice-growing regions in China during 2016–2020 were analyzed, and the cumulative risks of chronic and acute exposure to pesticides for the Chinese population were assessed. The QuEChERS extraction coupled with liquid chromatography-mass spectrometry for simultaneous determination of 25 pesticide residues in brown rice was developed and validated with good accuracy and precision (recoveries of 70%–120% and RSD ≤20%). The overall detection rate and over the maximum residue limit (MRL) rate of pesticides in brown rice decreased from 39.15% and 3.59% in 2016 to 34.11% and 1.53% in 2020, respectively. The Yangtze River basin had a higher detection rate and over MRL rate (43.14% and 2.88%, respectively) compared with the Southeast Coastal region (37.28% and 2.77%) and the Northeast Plain (11.28% and 0.17%). Isoprothiolane (13.57%) and carbendazim (8.32%) were the most frequently detected in rice samples. Pesticide residues exceeding the MRLs were found most often in triazophos (0.75%) and isocarbophos (0.51%). The risk ranking of pesticide residues based on the ranking matrix showed that carbofuran, methamidophos, and isocarbophos had the highest residual risk scores of 25.09, 25.01, and 25.00, respectively. 17.7% of rice samples contained two or more pesticide residues. The cumulative risk assessments based on the relative potency factor (RPF) approach revealed that the cumulative risks of chronic and acute dietary exposure to organophosphorus, neonicotinoid insecticides, and triazole fungicides from rice ranged from 7.43 × 10−4 to 3.36 × 10−2, which were not considered of health concern. The study provides national-scale information on the contamination levels and health risks of pesticide residues in rice, which can help develop continuous monitoring programs for pesticide residue contamination in rice in China. [ABSTRACT FROM AUTHOR]

Exploiting China's high-speed rail (HSR) as a quasi-natural experiment, we examine the relationship between the HSR connection and green innovation. The opening of HSR can promote green innovation by facilitating the flow of innovation factors. Using the multiperiod difference-in-differences (DID) model, we find that the regional green innovation performance significantly becomes better following the opening of HSR in the local city. Moreover, in examining the specific mechanisms at work, we find evidence that HSR stimulates green patents through increased labor mobility and research capital mobility. Further analyses show that the facilitating effect of HSR is heterogeneous among cities. Our paper sheds new light on the effects of HSR on social welfare in the case of sustainable economy. [ABSTRACT FROM AUTHOR]

Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China. We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18–70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4–6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov , NCT03134872 (follow-up is ongoing). Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0–14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6–15·4] vs 8·3 months [6·0–9·7]; hazard ratio 0·60 [0·45–0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1–positive population. Jiangsu Hengrui Medicine. [ABSTRACT FROM AUTHOR]

Based on the analysis of the high-speed rail industry chain, first, this paper divides the high-speed rail industry chain into infrastructure construction market and manufacturing market of mobile equipment and, second, this paper uses the empirical method of new experience industry organization to measure the market power premium of the high-speed rail upstream market. The study shows that the market power premium of the high-speed rail upstream market is 0.551, and the scale elasticity is 0.314, indicating that there is no systematic market power in the high-speed rail upstream market and there is significant scale diseconomy. The vertical market structure where "private enterprises dominate the upstream competition market and state-owned enterprises dominate the downstream oligopoly market" is further established. Based on the perspective of enterprises' entry in upstream markets, the social welfare of the high-speed rail industry market structure is analyzed. It is found in the study that the upstream market of the high-speed rail industry has a tendency of insufficient enterprise entry, and the total social welfare increases with the increase in the number of upstream enterprises entry. What is more, the profit of enterprises in the upstream market of high-speed rail decreases with the increase in the number of enterprises in the upstream. This paper believes that policies such as stimulating upstream high-speed rail enterprises entry, providing subsidies to upstream enterprises, reducing upstream enterprises' entry barriers, and expanding international markets can effectively improve the overall social welfare of the high-speed railway industry. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effects of a mind map‐based life review programme (MBLRP) on psychological distress, hope, meaning in life and self‐transcendence in cancer patients undergoing chemotherapy. Methods: Eighty‐four cancer patients undergoing chemotherapy from a university‐affiliated hospital in Fujian, China. The participants were randomly allocated to a MBLRP group (n = 40) or usual care group (n = 44). Data were collected at baseline (T0), on the second day (T1) and four weeks after the programme (T2) using the Distress Thermometer, Meaning in Life Questionnaire, Herth Hope Scale and Self‐transcendence Scale. Results: No significant interaction effects for time and group membership were found for psychological distress either at T1 (t = −1.707, p =.090) or at T2 (t = −1.123, p =.263). The interaction effects for T1 and group membership were statistically significant for meaning in life (t = 3.487, p =.001) and hope (t = 5.313, p <.001), but not statistically significant for self‐transcendence (t = 0.148, p =.882). The interaction effects for T2 and group membership were statistically significant for meaning in life (t = 2.592, p =.01), hope (t = 5.215, p <.001) and self‐transcendence (t = 2.843, p =.005). Conclusions: The MBLRP could improve hope, meaning in life and self‐transcendence in cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China.Methods: Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted.Results: Among mCRC patients (3878/8136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p < 0.001). The most common sequence from first- to second-line was from FOLFOX and other oxaliplatin-based regimens to FOLFIRI and other irinotecan-based regimens (286/1200, 24%).Conclusions: Our findings reflected a lack of consensus on the choice of third-line therapy and limited available options in China. It is evident o continue promoting early CRC diagnosis and to increase the accessibility of treatment options for mCRC patients. As the only nationwide large-scale study among CRC and mCRC patients before more biologics became available in China, our results can also be used as the baseline to assess treatment pattern changes before and after more third-line treatment were approved and covered into the National Health Insurance Plan in China between 2017 and 2018. [ABSTRACT FROM AUTHOR]

Nickel (Ni) concentrations in milled rice obtained from China and their variations among different provinces and varieties, as well as associated health risks, were investigated. Results showed that the mean Ni concentration in milled rice was 0.49 ± 0.51 mg/kg, which was much higher than reported in United Kingdom, French and Iranian cereals. There were significant variations (P < 0.05) of Ni concentrations in milled rice among different provinces and among varieties in the same province. According to the dietary risk assessment, the mean values of the target hazard quotient for chronic risk ranged from 1.24 to 1.46 for 2–4, 4–7 and 7–11-year-old children, and all values of margin of exposure for hypersensitivity risk were considerably below 10 for all age groups, indicating that the current dietary exposure to Ni in rice is of concern for 2–11-year-old children and Ni-sensitised individuals. It is essential to establish a continuous monitoring programme to control Ni contamination in rice. [ABSTRACT FROM AUTHOR]

Rapid economic development and industrialization may include environmentally harmful human activities that cause heavy-metal accumulation in soils, ultimately threatening the quality of the soil environment and human health. Therefore, accurate identification of pollution sources is an important weapon in efforts to control and prevent pollution. The self-organizing map (SOM) method is widely used in pollution source identification because of its capacity for visualization of high-dimensional data. The SOM ignores the graph structure relationship among chemical elements in soils; the SOM analysis of pollution sources has high uncertainty. Here, we propose a new analysis method, i.e., the graph convolutional self-organizing map (GCSOM), which uses a graph convolutional network (GCN) to extract the graph structure relationship among the chemical elements in soils, then performs data visualization using an SOM. We compared the performances of GCSOM and SOM, then assessed the pollution source characteristics of trace metal(loid)s (TMs, mostly heavy metals) in Jiangmen City using the GCSOM. Our experimental results showed that the GCSOM is superior to the SOM for identification of TM sources, while the TMs in the soil of Jiangmen originate from three main sources: agricultural activities (mainly in Taishan City, Jiangmen), traffic emissions (mainly in Xinhui and Pengjiang Districts), and industrial activities (mainly in Xinhui District). The risk assessment indicated that the risk of all TMs was within threshold. [Display omitted] • A new source analysis method named graph convolution self-organizing map is proposed. • The GCSOM shows a better performance than SOM in application. • Source tracing of HMs by GCSOM has been analyzed. • HMs in the soil of Jiangmen originate from agriculture, traffic and industrial activities. [ABSTRACT FROM AUTHOR]

The aim of this study is to report our experience with ductoscopic evaluation for screening patients with nipple discharge and evaluate any potential indications and benefits of ductoscopy. From January 2010 to December 2012, 419 female patients with nipple discharge were enrolled in this study. All patients involved in this study showed no mass in ultrasound and mammography. Data concerning age, clinical characteristics of nipple discharge, nipple discharge cytology, ductoscopic and postsurgical diagnosis, and complications were statistically analyzed. Ductoscopy examinations were completed in 405 patients (96.66%). For these 405 patients, there were 519 ductoscopic investigations. 112 (27.65%) patients were found to have intraductal papillary lesions of which 62 were operated in our hospital. Postsurgical diagnosis showed 8 (12.9%) malignancy including 6 DCIS and 2 invasive ductal carcinomas. All of the 8 patients meet at least two criteria of pathologic nipple discharge (single duct, spontaneous, bloody nipple discharge). The other patients with nonpapillary lesions are still under surveillance. By univariate analysis, patients with unilateral, single duct, spontaneous and bloody nipple discharge were more likely to have intraductal papillary lesions. By multivariate analysis, unilateral, spontaneous, and bloody nipple discharge showed statistically significant correlations with intraductal papillary lesions revealed by ductoscopy. Ductoscopy is a safe and efficient investigation in preoperative screening of the patients with nipple discharge. Clinical characteristics have predictive value in selection of patients for ductoscopical investigation. Patients with clinical characteristics of unilateral, spontaneous, and bloody nipple discharge were more likely to have intraductal papillary lesions revealed by ductoscopy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov , NCT03852251 , and closed to new participants; follow-up has been completed. Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3–4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1–17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3–42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0–15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2–40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7–19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7–37·4). Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. Akeso Biopharma. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Blocking the interaction between PD-1 and its ligands is a promising treatment strategy for advanced hepatocellular carcinoma. This study aimed to assess the antitumour activity and safety of the anti-PD-1 inhibitor camrelizumab in pretreated patients with advanced hepatocellular carcinoma.Methods: This is a multicentre, open-label, parallel-group, randomised, phase 2 trial done at 13 study sites in China. Eligible patients were aged 18 years and older with a histological or cytological diagnosis of advanced hepatocellular carcinoma, had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were randomly assigned (1:1) to receive camrelizumab 3 mg/kg intravenously every 2 or 3 weeks, via a centralised interactive web-response system using block randomisation (block size of four). The primary endpoints were objective response (per blinded independent central review) and 6-month overall survival, in all randomly assigned patients who had at least one dose of study treatment. Safety was analysed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT02989922, and follow-up is ongoing, but enrolment is closed.Findings: Between Nov 15, 2016, and Nov 16, 2017, 303 patients were screened for eligibility, of whom 220 eligible patients were randomly assigned and among whom 217 received camrelizumab (109 patients were given treatment every 2 weeks and 108 every 3 weeks). Median follow-up was 12·5 months (IQR 5·7-15·5). Objective response was reported in 32 (14·7%; 95% CI 10·3-20·2) of 217 patients. The overall survival probability at 6 months was 74·4% (95% CI 68·0-79·7)]. Grade 3 or 4 treatment-related adverse events occurred in 47 (22%) of 217 patients; the most common were increased aspartate aminotransferase (ten [5%]) and decreased neutrophil count (seven [3%]). Two deaths were judged by the investigators to be potentially treatment-related (one due to liver dysfunction and one due to multiple organ failure).Interpretation: Camrelizumab showed antitumour activity in pretreated Chinese patients with advanced hepatocellular carcinoma, with manageable toxicities, and might represent a new treatment option for these patients.Funding: Jiangsu Hengrui Medicine. [ABSTRACT FROM AUTHOR]

• It's the first basic study applied in tumor-bearing mice of gastric cancer in China. • Combination shows better efficacy in model by modulating the immune microenvironment. • This study provides a theoretical and scientific research basis for gastric cancer. To explore the effect of programmed death 1 (PD-1) inhibitor combined with apatinib on immune regulation and efficacy of the combined therapy in mice bearing gastric cancer (MBGC), and to provide a research basis for enhancing the benefit of immunotherapy in advanced gastric cancer (AGC). MBGC were divided into normal saline group (group NS), apatinib group (group A), PD-1 inhibitors group (group B) and PD-1 inhibitors combined with apatinib group (group C). Tumor inhibition rates were calculated. Cytokine levels and expression of immune cells and molecules were detected, and the pathological manifestations of tumor tissues were observed. Group C had the smallest tumor volume (115.17 ± 16.08 mm3) with a tumor inhibition rate of 89.4% ± 0.69%, significantly increased levels of CD4+T and CD8+T cells in tumor tissues (P < 0.01), the down-regulated proportion of myeloid-derived suppressor cells (MDSCs) (P < 0.01), and levels of PD-1 of CD8+T cells (PD-1+CD8+T) (P < 0.01). There was no difference in the levels of PD-1+CD8+T, CD4+T cells, and MDSCs between groups B and C. Besides, combination therapy increased the levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-ɑ (TNF-ɑ) in tumor tissue and serum. We also found that the anti-angiogenic effect of apatinib increased programmed death ligand-1 (PD-L1) levels, down-regulated vascular endothelial growth factor receptor 2 (VEGFR-2) levels, and induced an increase in the extent of tumor tissue necrosis. PD-1 inhibitors in combination with apatinib may help improve treatment outcomes and increase survival benefits in patients with AGC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects., Methods: This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study., Results: Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration-time curve from time zero to the last measurable concentration and area under the plasma concentration-time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported., Conclusions: Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food., Clinical Trial Registration: ClinicalTrials.gov NCT04057729., (© 2022. The Author(s).)

Aims: We aimed to explore whether visceral adiposity indices were significantly associated with obstructive sleep apnea (OSA) in type 2 diabetes (T2DM) patients., Methods: 100 patients with T2DM who underwent overnight polysomnography were analyzed in this study. Anthropometric data, lipid profiles, and glycemic parameters were recorded. Body fat percentage (BFP) and visceral adipose tissue area (VAT area) were collected from a whole body scan using dual-energy X-ray absorptiometry (DXA). Multivariate logistic regression analysis was performed to explore the associations of AHI with BFP, VAT area, and CVAI., Results: The prevalence rate of OSA was 80%, and the mean (±SD) of age was 47.0 ± 13.6 years. Apnea-hypopnea index (AHI) was significantly and positively associated with either VAT area ( r = 0.433, p ≤ 0.001) or Chinese visceral adiposity index (CVAI) ( r = 0.355, p ≤ 0.001) but not for BFP ( r = 0.107, p = 0.294). Multivariate logistic regression analyses showed that VAT area and CVAI were significantly associated with increased risk of OSA, and the adjusted ORs were (95% CI) 1.025 (1.003-1.047, p = 0.023) and 1.018 (1.002-1.034, p = 0.030), respectively. However, there was no significant association between BFP and increased risk of OSA., Conclusions: VAT area and CVAI were independent risk factors of OSA in the patients with T2DM., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Caiyu Zheng et al.)

Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai., Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings., Results: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae., Conclusions: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

Background: Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy., Methods: Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed., Results: With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including "red-nevus-like," "pearl-like," "mulberry-like," "patch-like," and "tumor-like," according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p < 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p < 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis., Conclusions: RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.

Objectives: To describe direct medical costs associated with each line of treatment among metastatic colorectal cancer (mCRC) patients in China. Methods: Electronic medical records between 2011 and 2016 were extracted from 12 tertiary hospitals in China for adult patients who initiated third-line treatment at least nine months before the end of data collection. Direct medical costs included costs of wards, diagnostic tests, surgical procedures, special materials, drugs and others. Costs were assessed by line of treatment, and drug costs were further breakdown for patients receiving chemotherapy alone and those receiving chemo- and biologics-combined therapy. Results: Of the 404 mCRC patients, the mean age was 55 years old and 62% were male. Oxaliplatin- and irinotecan-based regimens dominated first- and second-line treatment, respectively (44 and 37%). From first- to second- to third-line, the proportion of patients receiving targeted biologics increased from 18% at first-line and 12% at second-line to 34% at third-line; median number of treatment cycles reduced from 6 to 4 and to 2. The corresponding mean direct medical costs per person per cycle increased from $2,514 to $2,678 to $5,121. Mean drug costs per cycle increased from $2,314 to $2,673 to $4,316 among patients receiving chemotherapy alone and from $3,245 to $2,717 to $6,533 among patients receiving chemo- and biologics-combined therapy. Conclusions: Before 2017, mCRC patients in China did not receive the maximum benefits of precision medicine breakthroughs. Reduced treatment cycles and increased costs per cycle from first- to third-line suggested poor healthcare resource utilization. With earlier initiation and more treatment cycles, targeted biologics may better demonstrate their effectiveness among Chinese patients. Our findings reflected the urgent need to increase drug accessibility in China before 2017 and underscore that including innovative biologics into Chinese health insurance plans can reduce patients' economic burden and improve the management of mCRC.

Background: The incidence of cancer pain increases in discharged patients because of discontinued standard treatments and reductions in medication adherence. Motivated by the need for better pain management in discharged patients, we developed a mobile phone app (Pain Guard) to provide continuous treatment information and feedback to discharged cancer patients suffering from pain., Objective: The aim was to design, construct, and test the Pain Guard app in patients managing cancer pain, evaluate the total remission rate of pain and the improvement in quality of life (QoL) to improve pain management for cancer pain patients, and assess patient acceptance of the app., Methods: This randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned to a group receiving care through the Pain Guard app (n=31) or to a control group (n=27) who received only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. The system's usability, feasibility, app compliance, and satisfaction were also assessed. Our primary outcome was remission rate of pain, and secondary outcomes were medication adherence, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients., Results: All participants (N=58) successfully completed the study. There were no significant differences in baseline pain scores or baseline QoL scores between groups. At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (P<.001). The frequency of BTcP in the app group was considerably lower than that in the control group (P<.001). The rate of medication adherence in the trial group was considerably higher than that in the control group (P<.001). Improvements in global QoL scores in the trial group were also significantly higher than those in the control group (P<.001). The incidence of adverse reactions in the trial group (7/31) was lower than that in the control group (12/27), especially constipation, with significant differences (P=.01). The 31 participants in the trial group completed a satisfaction survey regarding Pain Guard: 23 (74%) indicated that they were satisfied with receiving pharmaceutical care by Pain Guard, 5 (16%) indicated that they were somewhat satisfied, 2 (6%) indicated neutral feelings, and 1 (3%) indicated that they were somewhat dissatisfied; no participants indicated that they were very dissatisfied., Conclusions: Pain Guard was effective for the management of pain in discharged patients with cancer pain, and its operability was effective and easily accepted by patients., Trial Registration: Chinese Clinical Trials Registry ChiCTR1800016066; http://www.chictr.org.cn/showproj.aspx?proj=27153., (©Jing Yang, Lizhu Weng, Zhikui Chen, Hongfu Cai, Xiaoyan Lin, Zhijian Hu, Na Li, Bijuan Lin, Bin Zheng, Qian Zhuang, Bin Du, Zhiyuan Zheng, Maobai Liu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 29.05.2019.)

Purpose: The aims of this study had been to classify the superior angle of the scapula based on morphological features, and to investigate its correlation with the suprascapular notch., Methods: 303 samples of Chinese dried scapular specimens were collected from the Department of anatomy, Southwest Medical University. According to the anatomical morphological characteristics of the superior angle of the scapula, the morphological classification was performed to explore its correlation with the suprascapular notch (SSN)., Results: The superior angle of the scapula was classified into three types (Hilly shape, Mountain Peak shape and Chimney shape). There were 143 cases of Hilly shape (47.20%), 144 cases of Mountain shape (47.52%), and 16 cases of Chimney shape (5.28%). The angle of Hilly shape (93.36° ± 7.76°) was significantly larger than the Mountain Peak shape (86.60° ± 6.61°) and the Chimney shape (86.22° ± 7.20°), and the difference was statistically significant (P < 0.05). The type I-III of Rengachary's classification to SSN was low risk of suprascapular nerve entrapment, while the type IV-VI was high risk of suprascapular nerve entrapment. Compared with the Mountain Peak shape and the Chimney shape, the Hilly shape corresponds to more types I-III of suprascapular notch but to fewer types IV-VI (P < 0.05)., Conclusions: The superior angle of the scapula was divided into three types: Hilly shape (47.20%), Mountain Peak shape (47.52%) and Chimney shape (5.28%). The Mountain Peak shape might be more likely to result in inability of the levator muscle with acute or chronic overload mechanisms, and the risk of suprascapular nerve entrapment in Mountain peak shape was higher than that of Hilly shape. And, it might have a potential effect on neck pain.

Objectives: The study was to investigate the prevalence and associated factors of erectile dysfunction (ED) in peritoneal dialysis (PD) patients., Methods: This was a cross-sectional survey. Eligible patients were interviewed by questionnaire: the five-item version of International Index of Erectile Function. Residual renal function (RRF) was assessed by daily urine volume and residual glomerular filtration rate., Results: Totally, 176 male prevalent PD patients were interviewed, six of them were not included in analysis for sexually inactive unrelated to ED. The prevalence of ED was 80.6 %. After adjusting for confounding factors, advance age (P = 0.014), less daily urine volume (P = 0.032) and higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.043) were independent risk factors for the development of ED., Conclusion: The prevalence of ED was high in Chinese PD patients. Advanced age, poor RRF and higher hs-CRP were independently associated with the prevalence of ED.

Purpose: To explore the effect of social support and coping style on depression in patients on CAPD in Southern China., Methods: The patients undergoing CAPD therapy for more than 3 months were recruited from Jan 1 to May 31, 2009. The Beck Depression Inventory-II (BDI-II), Social Support Rating Scale, Medical Coping Modes Questionnaire, and Medical Outcomes Study Short Form (SF-36) were used to evaluate depression, social support, coping style, and quality of life (QoL), respectively., Results: Of the 191 recruited patients, 65 patients (34.0 %) suffered from depression, with a BDI-II score of 23.8 ± 8.4. The average score of QoL (44.9 ± 13.9 vs. 64.7 ± 14.2, p < 0.001), social support (37.9 ± 7.2 vs. 42.1 ± 7.3, p < 0.001), and "confrontation" coping style (17.2 ± 3.9 vs. 18.8 ± 3.8, p = 0.006) in depressed patients was significantly lower than those in non-depressed patients, respectively. While the depressed patients had significantly higher score of "acceptance-resignation" coping style (12.9 ± 2.5 vs. 10.4 ± 3.5, p < 0.001) compared with those of non-depressed patients. Univariate analysis showed that the BDI-II score was negatively associated with social support (r = -0.284, p < 0.001) and "confrontation" (r = -0.180, p = 0.013), but positively associated with "acceptance-resignation" (r = 0.482, p < 0.001). Logistic regression analysis revealed that age (OR = 0.971, p = 0.038), female sex (OR = 2.211, p = 0.039), diabetes mellitus (OR = 3.046, p = 0.015), long PD duration (OR = 1.021, p = 0.020), fatigue (OR = 2.500, p = 0.032), high Pittsburgh Sleep Quality Index (PSQI) score (OR = 1.143, p = 0.001), low social support (OR = 0.945, p = 0.046), and high "acceptance-resignation" (OR = 1.096, p = 0.020) were independently associated with depression., Conclusion: There was a high prevalence of depression in CAPD patients. Age, female sex, diabetes mellitus, long PD duration, fatigue, sleep disturbance, low social support, and high "acceptance-resignation" coping style were independently associated with depression.