[Association between gestational diabetes mellitus and preterm birth subtypes].

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

[Development and application syndromic surveillance and early warning system in border area in Yunnan Province].

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

CaFeFeNbO6 - an iron-based double double perovskite.

Ordering of cations is important for controlling properties of ABO3 perovskites, and CaFeFeNbO6 is the first example of an Fe-based AA'BB'O6 double double perovskite, with Ca2+/Fe2+ ordered on A-site columns, and Fe3+/Nb5+ at the octahedral B-sites. Substantial (37%) antisite disorder of the latter cations leads to spin glassy magnetism below a freezing transition at 12 K. The CaMnFeNbO6 analogue also shows substantial cation disorder and spin glassy behaviour. Comparison of synthesis pressures for ordered materials based on different A-site transition metals, suggests that pressures of at least 14-18 GPa will be required to discover the expected plethora of double double perovskites based on A' cations smaller than Mn2+.

[Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma].

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

Author Correction: An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology.

Correction to: European Review for Medical and Pharmacological Sciences 2023; 27 (4): 1553-1564. DOI: 10.26355/eurrev_202302_31398-PMID: 36876711-published online on February 15, 2023. After publication, the authors applied some corrections to the galley proof: -       The order of Table I and II has been inverted. -       The scale bar of Figure 9A has been inserted in the Legend. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31398.

Oral Chinese Medicine for the treatment of targeted therapy-induced diarrhea: a systematic review and meta-analysis.

OBJECTIVE: The treatment of targeted therapy-induced diarrhea, a common adverse reaction of targeted therapy, with traditional Chinese medicine (TCM) has unique advantages; however, a unified TCM prescription is currently missing in clinical practice, and objective outcome indicators are lacking. Here, we aimed to provide medical evidence for the use of oral TCM in the treatment of targeted therapy-induced diarrhea. To this end, we systematically reviewed the literature evaluating the clinical efficacy of oral TCM for the treatment of targeted therapy-induced diarrhea. MATERIALS AND METHODS: The Chinese National Knowledge Infrastructure, China Biology Medicine disc, Technology Journal Database, Wanfang Medical Network, PubMed, Cochrane Library, EMBASE, MEDLINE, and OVID databases were used for a literature search of clinical randomized controlled trials examining the use of oral TCM in the treatment of targeted therapy-induced diarrhea until February 2022. A meta-analysis was performed using RevMan 5.3 software. RESULTS: In total, 490 relevant studies were screened, 480 were excluded based on the inclusion and exclusion criteria, and 10 clinical studies were finally included. The 10 studies included a total of 555 patients: 279 in the treatment group and 276 in the control group. The improvements in total clinical efficiency, TCM syndrome score, and graded efficacy of diarrhea in the treatment group were better than those in the control group (p<0.01); however, there was no difference in the Karnofsky Performance Scale score between the groups. The funnel plot for total clinical efficiency was symmetrical, and the publication bias was found to be low. CONCLUSIONS: Oral TCM is an effective treatment for targeted therapy-induced diarrhea and can significantly improve the clinical symptoms and quality of life of patients.

[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

A 2-Stage Root Analog Implant with Compact Structure, Uniform Roughness, and High Accuracy.

Immediate implant placement has the advantages of shortening the operation time, reducing the treatment cycle and cost. At present, this technology has been used widely, but the indications of immediate implantation are still limited. Here, a novel type of root analog implant (RAI) was manufactured by selective laser melting technology to address the limitation. Under optimized condition, RAIs were printed with the internal density of 99.73% and the uniform surface roughness of 11 µm (Sa). Besides, the deviation between RAI specimen and design models is controlled within 0.15 mm after optimizing scanning parameters. The substrate printed could promote human bone marrow stromal cell proliferation, spreading, and osteogenic differentiation. The bone-implant contact (BIC, 75% ± 7%) and bone volume/total volume (BV/TV, 74% ± 7%) of RAIs were significantly higher than that of conventional implants (BIC, 66% ± 5%; BV/TV, 62% ± 5%) in in vivo experiments. Further, customized abutments were designed for the RAIs, improving the masticatory ability of the beagle dogs after crown restoration. This study aims to design a personalized 2-stage RAI with compact structure and uniform roughness, in order to achieve better fracture resistance, initial osseointegration efficiency, and dispersed stress in immediate implantation. It provides a certain guiding value for standardizing the manufacture and clinical application of RAI in immediate implantation.

An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology.

OBJECTIVE: Surgery and radioactive iodine therapy are the main treatments for papillary thyroid carcinoma (PTC), and effective drugs are lacking. As a promising natural product, nobiletin (NOB) has a wealth of pharmacological activities like anti-tumor, antivirus, and other effects. In this research, bioinformatics methods and cellular assays were combined to explore how NOB inhibited PTC. MATERIALS AND METHODS: Our NOB targets were derived from three databases, including the SwissTargetPrediction database, Traditional Chinese Medicine System Pharmacology Database, and the TargetNet server. Four databases were used to identify disease-related targets: GeneCards, PharmGkb, Online Mendelian Inheritance in Man, and DisGeNET. Finally, cross-targets of disease and drug were deemed as pharmacological targets, and they were used for GO and KEGG enrichment analysis. STRING and Cytoscape were applied for PPI Network and core Targets Ranking. Molecular docking analysis validated binding affinity values for NOB and core targets. By using cell proliferation and migration assays, NOB was assessed for its effects on PTC proliferation and migration phenotype. Western blot validated the downregulation of the PI3K/Akt pathway. RESULTS: (1) Preliminarily, 85 NOB targets were predicted for NOB intervention in PTC. (2) Our core target screening identified TNF, TP53, and EGFR, and our molecular docking results confirmed good binding between NOB and protein receptors. (3) NOB inhibited proliferation and migration of PTC cells. PI3K/AKT pathway target proteins were downregulated. CONCLUSIONS: (1) Bioinformatics analyses revealed that NOB may inhibit PTC by regulating TNF, TP53, EGFR and PI3K/AKT signalling pathway. (2) As evidenced by cell experiments, there was an inhibition of proliferating and migrating PTCs by NOB via the PI3K/AKT signalling pathway.

Probing the pressure dependence of sound speed and attenuation in bubbly media: Experimental observations, a theoretical model and numerical calculations.

The problem of attenuation and sound speed of bubbly media has remained partially unsolved. Comprehensive data regarding pressure-dependent changes of the attenuation and sound speed of a bubbly medium are not available. Our theoretical understanding of the problem is limited to linear or semi-linear theoretical models, which are not accurate in the regime of large amplitude bubble oscillations. Here, by controlling the size of the lipid coated bubbles (mean diameter of ≈5.4µm), we report the first time observation and characterization of the simultaneous pressure dependence of sound speed and attenuation in bubbly water below, at and above microbubbles resonance (frequency range between 1-3 MHz). With increasing acoustic pressure (between 12.5-100 kPa), the frequency of the peak attenuation and sound speed decreases while maximum and minimum amplitudes of the sound speed increase. We propose a nonlinear model for the estimation of the pressure dependent sound speed and attenuation with good agreement with the experiments. The model calculations are validated by comparing with the linear and semi-linear models predictions. One of the major challenges of the previously developed models is the significant overestimation of the attenuation at the bubble resonance at higher void fractions (e.g. 0.005). We addressed this problem by incorporating bubble-bubble interactions and comparing the results to experiments. Influence of the bubble-bubble interactions increases with increasing pressure. Within the examined exposure parameters, we numerically show that, even for low void fractions (e.g. 5.1×10-6) with increasing pressure the sound speed may become 4 times higher than the sound speed in the non-bubbly medium.

[Effect of preoperative anterior bony impingement on lateral collateral ankle ligament reconstruction].

Objective: To explore whether the combination of anterior bony impingement before surgery will affect the efficacy of the lateral collateral ankle ligament reconstruction surgery in patients with chronic ankle instability (CAI). Methods: A prospective cohort study. Patients with CAI who underwent lateral collateral ankle ligament reconstruction from January 2014 to October 2017 in the Department of Sports Medicine, Huashan Hospital, Fudan University were enrolled in this study. The patients were divided into no bony impingement group (NI group) and bony impingement group (BI group) according to the presence of bone impingement in front of the ankle during the operation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson ankle functional socre (KAFS), Tegner score, visual analogue scale (VAS) of pain were extracted and were reevaluated at least 2 years after surgery as well as imaging evaluation of ankle. Results: A total of 59 patients were enrolled in this study. There were 29 patients in the NI group, 23 males and 6 females with a mean age of (28.4±7.1) years. And there were 30 cases in the BI group, 28 males and 2 females with a mean age of (31.9±8.6) years. The AOFAS, KAFS and Tegner scores in NI group increased from 65.8±10.6, 65.9±10.1 and 3.0 (3.0, 4.0) before the operation to 97.5±4.3, 97.8±4.7 and 6.0(5.0,6.0) after the operation, respectively; and the VAS decreased from 3.0(3.0, 4.0) to 0(0, 0); there were significant differences in those indexes before and after the operation (all P<0.05). The scores of AOFAS, KAFS and Tegner in BI group increased from 65.2±11.0, 64.2±10.0 and 3.0(3.0, 4.0) before the operation to 97.1±4.3, 97.3±4.3 and 5.0(4.0, 6.0) post the operation, respectively; and the VAS scores decreased from 3.0(3.0, 5.0) to 0(0, 1.0); there were significant differences in up-mentioned indexes before and after the surgery (all P<0.05). There was no significant differences in baseline and preoperative clinical function scores between the two groups (all P>0.05). No significant difference was found in postoperative AOFAS, KAFS and VAS scores between the two groups (all P>0.05), while postoperative Tegner score in the NI group was significantly higher than that in the BI group [6.0(5.0, 6.0) vs 5.0(4.0, 6.0), P=0.026]. Imaging evaluation of all patients showed that the reconstructed ligament was clearly visible, and the intraarticular injuries existing before surgery showed obvious signs of healing. Conclusion: Ankle lateral collateral ligament reconstruction for CAI with or without anterior bony impingement results in similar outcomes in ankle function, stability and pain levels.

[Early results of left ventricular assist device implantation for the treatment of heart failure].

Twenty-four male patients who underwent left ventricular assist device (LVAD) implantation due to advanced heart failure in Union Hospital, Fujian Medical University from June 2019 to June 2022 were retrospectively included. The age of patients was 32-61 (48.4±8.4) years. Everheat-Ⅰ, HeartCon and Corheart 6 left ventricular assist systems were used in 10, 6 and 8 cases, respectively. All patients were discharged successfully without mechanical failure, thrombosis or secondary thoracotomy for hemostasis. Early postoperative hemodynamics were significantly improved, left ventricular systolic diameter was reduced, left ventricular ejection fraction was gradually improved, and no hemolysis occurred. The patients were followed up for 3 to 39 (17.9±8.6) months, the cardiac function was restored to grade Ⅰ to Ⅱ, and the 6-minute walking test distance increased significantly. Therefore, satisfactory early results can be achieved with left ventricular assist device implantation for the treatment of heart failure.

[Optimized pathway to schistosomiasis elimination in China: a scrutiny using a marginal benefit approach].

Following concerted efforts for over 7 decades, great achievements have been gained in the national schistosomiasis control program of China. Currently, China is moving towards the stage of schistosomiasis elimination, when the major task is to make full use of available resources to improve schistosomiasis surveillance and response to sustainably consolidate gained schistosomiasis control achievements and prevent re-emerging schistosomiasis. There is therefore an urgent need for optimization of interventions for schistosomiasis elimination. Based on analysis of socioeconomic features at different stages of the national schistosomiasis control program in China, this review discusses the relationship between the needs of assessment of schistosomiasis elimination interventions and the optimized strategy of schistosomiasis elimination at different stages of the national schistosomiasis control program using a marginal benefit approach and proposes the optimized schistosomiasis elimination strategy that allows the highest marginal benefit with currently available schistosomiasis elimination costs, so as to provide the optimal strategic pathway to schistosomiasis elimination and facilitate the achievement of the targets set in Healthy China 2030.

[Prevalence and molecular characterization of Cryptosporidium in captive-bred Mustela putorius furo in Jiangsu Province].

OBJECTIVE: To investigate the prevalence and molecular features of Cryptosporidium in captive-bred Mustela putorius furo in Jiangsu Province. METHODS: A total of 290 fresh stool samples were collected from a ferret farm in Jiangsu Province on May 2017, and the small subunit rRNA (SSU rRNA) gene of Cryptosporidium was amplified in stool samples using nested PCR assay. The actin, cowp and gp60 genes were amplified in positive samples and sequenced to characterize Cryptosporidium species/genotypes. RESULTS: A total of 18 stool samples were tested positive for Cryptosporidium SSU rRNA gene, with a detection rate of 6.2%. Sequence and phylogenetic analyses of SSU rRNA, actin and cowp genes characterized Cryptosporidium isolated from captive-bred ferrets as Cryptosporidium sp. ferret genotype. In addition, gp60 gene was amplified in 10 out of 18 stool samples tested positive for Cryptosporidium. CONCLUSIONS: Cryptosporidium is widely prevalent in captive-bred ferrets in Jiangsu Province, and Cryptosporidium sp. ferret genotype is the only Cryptosporidium genotype in ferrets.

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue.

PURPOSE: The role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage. RESULTS: Of the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR=0.71 [0.65-0.78]) and (HR=0.66 [0.59-0.74]), respectively, but not in patients with stage III/IV (HR=1.01 [0.80-1.26]) and (HR=0.93 [0.67-1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index=0.749±0.002). CONCLUSION: This cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.

[Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma].

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.