Volume 102 ·  Issue 32 ·  2022

Artificial intelligence (AI) is widely used in the current medical field at home and abroad, including medical imaging, auxiliary diagnosis, drug research and development, health management, disease prediction and other fields, but its "autonomy" and "unknownness" have brought great challenges to the current legal system, especially the subject positioning of AI medical care and the identification of legal responsibilities. We should effectively analyze the development trend of the future role of AI medical care, put forward countermeasures in advance at the legal level to prevent problems before they occur targeting the problems of AI medical development, in order to promote the effective regulation of the application of AI medical care, and thus ensure its healthy development in China.

The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial.

A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed.

For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus.

The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

To evaluate the incidence of thromboembolism in a cohort of patients with lung cancer who received immune checkpoint inhibitors (ICIs), and explore relevant clinical risk factors.

We retrospectively collected and analyzed the clinical data of patients with confirmed primary lung cancer and treated with ICIs between March 2018 and June 2021 at three hospitals in China (Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Fudan University Shanghai Cancer Center and Zhongshan Hospital of Fudan University). The cumulative incidence and risk factors of thromboembolism in these patients were analyzed using a competitive risk model.

A total of 804 patients were enrolled, there were 623 males and 181 females, with a median age of 59 years (ranged 28-86 years). Of these, 62 patients encountered 65 thromboembolic events, including 51 venous thromboembolism events (VTE) and 14 arterial thromboembolism events. The cumulative incidence of thromboembolism events at 3, 6, 12 and 24 months were 4.3%, 6.1%, 10.1% and 16.8%, respectively. And the cumulative incidence of venous thromboembolism events at 3, 6, 12 and 24 months were 3.4%, 4.7%, 9.0% and 13.3%, respectively. Multivariate analysis showed that history of thromboembolism (HR=6.345, 95%CI: 2.917-13.802,P<0.001),liver metastasis (HR=2.249, 95%CI: 1.123-4.502,P=0.022) and peripherally inserted central venous catheter (HR=3.674, 95%CI: 1.751-7.712, P<0.001) were independent risk factors for venous thromboembolism during ICIs therapy in patients with lung cancer.

Patients with lung cancer under ICIs therapy are at high risk of thromboembolism. And history of thromboembolism, liver metastasis and peripherally inserted central venous catheter are risk factors of venous thromboembolism.

To explore the risk factors related to cesarean scar pregnancies (CSP).

Among the patients during July 2016 to June 2021 in Peking University Third Hospital, 596 cases of CSP patients were included as study group, and 1 192 cases of intrauterine pregnancy(IUP) women with history of cesarean section(s) were chosen as control group through stratified sampling according to the civil year of previous cesarean section matched with CSP group. The correlation between the general situation of patients, the history of gravidity and parity, the history of surgeries in uterine cavity and the previous cesarean section and the occurrence of CSP was explored through multivariate logistic regression analysis.

The current age of 596 CSP patients was (34.6±4.4) years, and that of 1 192 IUP patients was (35.6±3.6) years (P<0.001). Multivariate logistic regression analysis showed that the following factors may increase the risk of CSP: age<35 years old (OR=2.306, 95%CI: 1.774-2.998), history of medical abortion (OR=1.629, 95%CI 1.102-2.407), pregnancy interval<2 years from the last cesarean section (OR=2.147, 95%CI: 1.237-3.726), pregnancy interval ≥8 years from the last cesarean section (OR=1.474, 95%CI: 1.110-1.957), history of surgeries in uterine cavity before the last cesarean section (OR=2.558, 95%CI: 1.809-3.615), history of surgeries in uterine cavity after the last cesarean section (OR=8.020, 95%CI: 5.966-10.781), previous cesarean delivery ≥2 times (OR=14.051, 95%CI: 9.699-20.356) and history of previous cesarean sections before labor (OR=2.683, 95%CI: 1.930-3.731)(all P<0.05).

The occurrence of CSP is related to the age of patients, the history of medical abortion, pregnancy interval, the history of surgeries in uterine cavity and the previous cesarean section, among which previous cesarean delivery ≥2 times and history of surgeries in uterine cavity after the last cesarean section are the strongly associated risk factors.

To study the value of molecular classification in postoperative adjuvant therapy for endometrial carcinoma (EC).

Patients with stage Ⅰ EC who underwent surgical-pathological staging surgery and molecular classification in Peking University Third Hospital from January 2020 to April 2022 were retrospectively analyzed. The influence of different molecular types of EC on postoperative adjuvant therapy were studied.

The age of the 196 patients was (55.1±10.2) years old, and the body mess index (BMI) was (26.0±3.9) kg/m². Molecular classification was performed in 196 stage ⅠEC patients, identifying the 4 subgroups: POLE mutation (POLEmut, n=19, 9.7%), mismatch repair-deficient (dMMR, n=28, 14.3%), no-specific molecular profile (NSMP, n=142, 72.4%) and p53 mutation (p53abn, n=7, 3.6%). Molecular classification was one of the influencing factors on the selection of postoperative adjuvant therapy for EC patients (P=0.003). POLEmut, dMMR and NSMP subtypes were not the variables in selecting radiotherapy or combined chemo-radiotherapy postoperatively. p53abn subtype was not the influencer for radiotherapy, however, it may contribute to the selection of combined chemo-radiotherapy postoperatively (P<0.001).

The p53abn subtype in the molecular classification is an influencing factor in the selection of combined chemo-radiotherapy for EC patients postoperatively.

To analyze clinicopathological characteristics of patients with uterine papillary serous carcinoma (UPSC) in China, and investigate roles of TXNDC17 protein in UPSC clinicopathological characteristics and prognosis.

Fifty-five patients with UPSC treated in Women′s Hospital School of Medicine Zhejiang University from 2003 to 2016 were analysed retrospectively. Immunohistochemistry (IHC) were performed to TXNDC17 and BECN1 (Beclin 1 protein, a key regulator of autophagy) protein expression respectively. Kaplan-Meier was used to calculate the cumulative survival rate, Log-rank test was performed to compare the difference in cumulative survival rate among patients with different clinicopathological characteristics, and Cox regression model was used to analyze the related between TXNDC17 expression and prognosis of UPSC patients.

The median age of the 55 UPSC patients was 63(49, 79) years, 43.6%(24/55) with late stages (stage Ⅲ/Ⅳ), and 32.7 % (18/55) exhibiting more than half of myometrium invasion were enrolled. Notably, 28 (50.9%) patients had TXNDC17 protein overexpression, and associated with BECN1 overexpression(P=0.023). Besides, co-expression of TXNDC17 and BECN1 occurred at an advanced stage and deep myometrial invasion (P=0.013,0.009). The cumulative survival rate of TXNDC17 overexpression(37.4% vs 91.5%),FIGO Ⅲ/Ⅳ stage(44.1% vs 70.1%), deep myometrium invasion(36.1% vs 75.4%) and BECN1 overexpression(0 vs 83.0%)patients was low (P<0.05). The multivariate proportional hazards model revealed that myometrial invasion and TXNDC17 overexpression were associated with prognosis of UPSC patients.

This study shows that TXNDC17 overexpression is associate with poor survival in UPSC patients. Co-expression of TXNDC17 and BECN1 shows characteristics of advanced stages and deep myometrial invasion. TXNDC17 may be a potential predictor or target in UPSC therapeutics..

The present study aimed to investigate the associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms with the risk of Crohn′s disease (CD) in Chinese patients.

From January 2012 to January 2021, a total of 207 CD patients and 545 age-and gender-matched healthy controls were collected from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The genotypes of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression analysis was used to analyze the differences of CDKN2B-AS1 polymorphisms between CD patients and healthy controls, as well as their influences on the clinicopathologic characteristics of CD patients. The analyses for linkage disequilibrium and haplotype were further performed by Haploview 4.2 software.

The variant genotype (AG+GG) and variant allele (G) of rs1063192 were more prevalent in CD patients than in healthy controls (32.4% vs 24.8%, P=0.036; 18.8% vs 13.6%, P=0.011). The same conclusions were also drawn for homozygous variant genotype (GG) and variant allele (G) of rs10757274 when CD patients were compared with healthy controls (19.8% vs 12.8%, P=0.017; 45.2% vs 38.1%, P=0.012). According to the Montreal Classification Standards, CD patients were stratified into different subgroups. The homozygous variant genotype (GG) and variant allele (G) of rs10757278 were less frequent in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (13.7% vs 29.9%, P=0.015; 37.7% vs 50.4%, P=0.022). However, all the correlations above were no longer significant after Bonferroni′s correction (all P>0.05). The polymorphic loci of rs10757274, rs2383207, rs10757278, and rs1333048 were in close linkage disequilibrium with each other in CDKN2B-AS1 gene. Compared with healthy controls, the frequency of haplotype AGAC was decreased in CD patients (1.5% vs 4.5%, χ2=7.61, P=0.006), whereas the frequency of haplotype GGAC was obviously increased in CD patients (3.0% vs 0.6%, χ2=14.25, P<0.001). The stratified analysis further showed that the frequency of haplotype AGAC was higher in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (3.1% vs 0.4%, χ2=5.31, P=0.021).

The variations of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) may not independently affect the risk of CD. Among the haplotypes constructed by rs10757274, rs2383207, rs10757278, and rs1333048, the haplotype AGAC may reduce the risk of CD, whereas it may increase the risk of stricturing or penetrating in CD patients. In addition, the haplotype GGAC may increase the risk of CD.

To compare the clinical characteristics and survival outcomes of multiple myeloma (MM) with second primary malignancies (SPMs) and MM secondary to malignancies.

The clinical data of MM patients diagnosed and treated in Beijing Chaoyang Hospital, Capital Medical University from January 2002 to January 2021 were included. The patients were divided into two groups: MM with SPMs group and MM secondary to malignancies group. The gender, age at first diagnosis, classification, stage, type of combined malignant tumor and the treatment were analyzed. The clinical characteristics and survival differences were compared between the two groups.

There were 20 patients in the MM with SPMs group, 9 males and 11 females, aged [M(Q₁,Q₃)] 61.5(56.8, 68.0)years, and the overall survival (OS) was 49.5(32, 58) months, while the time to death from secondary tumor was 12(4,21)months. There were 29 patients in the MM secondary to malignancies group, 13 males and 16 females, aged 64.0(57.0, 71.0)years, and the OS was 97(61, 171) months, while the time to death from secondary MM was 32(18, 47) months. The time from patients diagnosed with MM to SPMs was 37(18, 50) months, which was significantly earlier than that of MM secondary to malignancies [53(31,117) months](P=0.016). The type of tumor was also different between the two groups (P<0.001). In the group of MM with SPMs, the most common type of SPMs was hematopoietic malignancies (12/20, 60.0%), whereas in the group of MM secondary to malignancies, MM was most often secondary to genitourinary malignancies (13/29, 44.8%) (P<0.001).

Both MM with SPMs and MM secondary to malignancies can affect the survival of patients. Secondary hematological malignancies account for a high proportion of the second tumors in MM patients, while genitourinary malignancies account for a high proportion of malignant tumors associated with MM.

To explore the etiology of hemophagocytic lymphohistiocytosis (HLH) and analyze the clinical features, treatment options and outcomes of patients with HLH induced by infectious and non-infectious factors.

The clinical data of 97 patients aged ≥14 years who were diagnosed or suspected of HLH during their hospitalization at Peking University First Hospital from January 1, 2006 to December 4, 2021 were retrospectively analyzed, and 80 patients with HLH were further screened for inclusion. The general condition and etiological composition of the patients were analyzed, and the laboratory tests, treatment and outcome of patients in the infection, tumor and autoimmune disease groups were compared.

The age[M(Q₁,Q₃)] of the 80 patients with HLH was 53.5 (32.0, 64.0) years, with a male-to-female ratio of 1∶1. Of the 80 HLH patients with HLH, 23.8% (19/80)、37.5% (30/80)、15.0% (12/80)、10.0% (8/80) were secondary to infection, neoplasm, autoimmune disease, and mixed factors, respectively, with EBV infection (n=15) and hematologic neoplasm (n=28) being the most common etiologies in infection or non-infection-related HLH. The incidence of peripheral blood secondary or tertiary lineage reduction was significantly higher in patients in the infection group than in the autoimmune disease group [68.4% (13/19), 33.3% (4/12), P=0.002]. Serum ferritin (SF) ≥500 μg/L and ≥1 500 μg/L were 93.1% (54/58) and 72.4% (42/58), respectively; among them, 29 patients had significantly lower SF after treatment than before treatment, 1 049 (362, 1 769)μg/L and 2010 (1 231, 7 323) μg/L (P<0.001). Phagocytosis was seen in 68.75% (55/80) and HLH-related gene mutations were detectable in 5 cases. In the three groups, 13.1% (8/61) of patients died of disease, 47.5% (29/61) improved and 9.8% (6/61) relapsed.

HLH has no specific symptoms and progresses rapidly, mainly due to infections, neoplastic diseases, autoimmune diseases. The prognosis may be improved with early treatment.

This study aimed to build a home use deep learning segmentation model to identify the scope of caries lesions. A total of 494 caries photographs of molars and premolars collected via endoscopy were selected. Subsequently, these photographs were labeled by physicians and underwent segmentation training by using DeepLabv3+, and then verification and evaluation were performed. The mean accuracy was 0.993, the sensitivity was 0.661, the specificity was 0.997, the Dice coefficient was 0.685, and the intersection over union (IoU) was 0.529. Therefore, the present deep learning segmentation model can identify and segment the scope of caries.

This paper reports a case of difficult rare disease GATA2 deficiency syndrome presented with the clinical phenotypes of monopenia with mycobacterial infection syndrome and alveolar proteinosis. A 14-year-old female was admitted for "fever, cough and sputum for 2 months". Post-admission examination revealed Mycobacterium avium lung disease complicated with pulmonary alveolar proteinosis, and combined with the patient's anemia, leukopenia, obvious monocytopenia and gene sequencing results to diagnose GATA2 deficiency syndrome. Clinical and pulmonary imaging improved significantly after anti-infective treatment. The disease has great heterogeneity, complex and diverse phenotypes, and is easy to be misdiagnosed and misdiagnosed. It is necessary to improve the identification of non-tuberculous mycobacterial infection risk factors and secondary factors of pulmonary alveolar proteinosis in clinic, especially to expand and deepen the diagnosis and treatment of rare factors such as GATA2 deficiency syndrome.

With the widespread use of immune checkpoint inhibitors (ICIs) in clinical practice, their related toxicity has attracted more and more attention. ICIs-related adverse reactions include immune-related adverse events (irAEs) and infusion reactions. Most irAEs were mild and improved after symptomatic treatment. Severe irAEs have low incidence, dangerous onset, rapid progression and high mortality. This article reports a young male patient with primary refractory classical Hodgkin's lymphoma. After partial remission of rescue chemotherapy, autologous peripheral blood stem cell transplantation was performed, followed by maintenance therapy with programmed cell death receptor 1 (PD-1) inhibitor. During the process, chest tightness and fatigue, amaurosis, diarrhea, increased blood sugar and abnormal myocardial enzymology appeared delayed, followed by slowed heart rate and decreased blood pressure. Considering the combination of irAEs, the effect of glucocorticoid treatment was not good, and the condition deteriorated rapidly. This case suggests that there is a possibility of delayed irAEs in patients clinically treated with PD-1 inhibitors, and it is necessary to strengthen vigilance and diagnose and treat as soon as possible.

Pan-apoptosis is a kind of inflammatory programmed cell death, which is regulated by pan-apoptotic body complex and has the key characteristics of pyroptosis, apoptosis and necrotic apoptosis. It is undoubtedly the hotspot and focus of programmed cell death research in the future. At present, studies have confirmed that pan-apoptosis is closely related to infectious diseases, tumors and other human diseases. Although its specific regulatory mechanism is not clear, as a potential intervention target, pan-apoptosis has shown good research prospects. A comprehensive understanding of the research progress of the role of pan-apoptosis in human diseases is expected to explore a new treatment strategy and bring breakthroughs for the treatment of related patients to clarify the role and regulatory mechanism of pan-apoptosis in human diseases.

CD5 antigen-like protein (CD5L) is a soluble glycoprotein that binds to its corresponding receptor to exert different biological effects. In recent years, the role of CD5L in kidney diseases has been gradually paid attention to. This paper reviews the biological function of CD5L and its recent research progress in acute kidney injury and chronic kidney disease.

Cardiovascular disease (CVD) is the most common cause of death in patients with rheumatoid arthritis (RA), and dyslipidemia is an important traditional CVD risk factor. However, under the influence of inflammatory processes, active RA patients usually have low density lipoprotein cholesterol (LDL-C) low levels, resulting in their CVD risk that is often underestimated, namely the lipid paradox. Traditional lipid profiles do not reflect the risk of CVD in patients with RA. The development of novel "non-traditional" lipid parameters is important for further evaluation of lipid alterations in RA, and identification of CVD risk is important for patients with active RA. This article reviews the research progress of dyslipidemia and the risk of CVD in patients with rheumatoid arthritis.

The handover of intraoperative anesthesia management is common. Shift handover can reduce the fatigue of anesthesiologists and improve the quality of anesthesia management, but at the same time, it may bring the risk of loss of critical information of patients. Several large observational studies have reported the relationship between intraoperative anesthesia management handover and postoperative complications, but the findings are inconsistent. Researchers from the University of Münster School of Medicine in Germany designed a multicenter randomized trial to clarify the impact of intraoperative anesthesiologist shift handover on postoperative mortality, readmission, and complications in adult patients. The study included American Society of Anesthesiologists (ASA) Grade 3 or 4 adult patients who underwent major elective surgery at 12 medical centers in Germany between June 2019 and June 2021 with an expected surgery time of more than 2 hours and were randomly assigned to either the complete or no-handover anesthesia management group. None of the participating institutions used standardized handover procedures, and the handover content was carried out according to the custom of our hospital. Primary outcome measures: combined outcomes of all-cause mortality, readmission, or severe postoperative complications within 30 days of surgery. Secondary endpoint: A total of 19 secondary endpoint measures, including all-cause mortality within 30 days after surgery, single outcome of readmission or severe postoperative complications, time of admission to intensive care unit (ICU) and length of hospital stay, etc. A total of 1 817 patients were enrolled in the study, of which 1 772 patients completed the trial. Patients were (66 ± 12) years old, 997 patients were male (56%), and 1 717 patients had ASA grade 3 (97%). The median total anesthesia time in the complete handover anesthesia management group was 267 min (IQR: 206 to 351 min), and the median time from start of anesthesia to shift handover was 144 min (IQR: 105-213 min). In the complete anesthesia management group (891 patients), 268 patients (30%) experienced a primary outcome event compared to 284 patients (33%) in the non-anesthesia management group (881 patients) (absolute risk difference: -2.5%, 95%CI：-6.8%~1.9%；OR=0.89，95%CI：0.72~1.10，P=0.27）； All-cause mortality within 30 days after surgery was 2.1% and 3.4% in both groups (absolute risk difference: -1.3%, 95%CI：-2.8%~0.2%；OR=0.61，95%CI：0.34~1.10，P=0.11）； The readmission rates were 13% and 16% in both groups (absolute risk difference: -2.7%, 95%CI：-5.9%~0.6%；OR=0.80，95%CI：0.61~1.05，P=0.12）； The incidence of severe postoperative complications was 21.9% and 21.6% (absolute risk difference: 0.3%, 95%CI：-3.6%~4.1%；OR：1.02，95%CI：0.81~1.28，P=0.91）。 There were no significant differences in the 19 secondary endpoints between the two groups. This study suggests that there is no significant difference in the combined outcome of mortality, readmission, or severe postoperative complications within 30 days after surgery for adult patients undergoing routine surgery.

Studies have confirmed alterations in the composition and function of the gut microbiota in women with fibromyalgia, including changes in the relative abundance of certain bile acid metabolizing bacteria. Bile acids can affect a variety of physiological processes, including visceral pain, but there are no studies exploring their relationship with the gut microbiota in patients with fibromyalgia. Researchers from McGill University Health Center in Canada used 16S rRNA sequencing and targeted metabolomics to study the characteristics of gut microbiota and circulating bile acids in 42 female patients with fibromyalgia and 42 healthy controls. It was found that the relative abundance of several bacteria known to metabolize bile acids was altered in female patients with fibromyalgia, accompanied by changes in serum concentrations of secondary bile acids, including a significant depletion of alpha-murine cholic acid. Statistical learning algorithms based on these serum bile acid concentrations can accurately identify patients with fibromyalgia. At the same time, serum alpha-murine cholic acid was highly correlated with symptom severity, including pain intensity and fatigue. The above findings suggest that alterations in serum bile acids are associated with nociceptive plastic pain, and the changes in gut microbiota composition and circulating secondary bile acid concentrations observed in the study appear to be consistent with the phenotype of increased nociception and strongly correlated with symptom severity. This study is the first to prove that changes in circulating bile acids in patients with fibromyalgia may be secondary to changes in the upstream intestinal microbiota. If it can be confirmed in other independent studies, the results of this study may help to develop molecular diagnostic aids for fibromyalgia and elucidate the pathogenesis of fibromyalgia syndrome.