ObjectiveTo analyze the development trajectory， research hotspots， and trends in medical humanities research in China since the new era. MethodsA search was conducted on the CNKI （China National Knowledge Infrastructure） advanced search page using the themes“medical humanities”or “humanistic medicine，”retrieving a total of 5，758 articles. After applying specific screening criteria， 5，095 articles were included in the analysis. Citespace6.1.R6 was used to visualize and analyze the authors， institutions， and keywords of the 5，095 articles. ResultsSince the new era， the volume of publications on medical humanities in China has shown an overall upward trend， with limited collaboration between core institutions and core authors. The research content of medical humanities has evolved from broad to specific， from abstract to concrete， and from theoretical to practical. ConclusionThe development of medical humanities research in China has generally gone through three stages： defining related concepts， integrating medical humanistic spirit into clinical practice， and applying empirical methods. Narrative medicine， ideological and political education in curricula， and medical humanities education are potential future research directions.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

The effects of host factors ADP-ribosylation factor 4 (ARF4) and ADP-ribosylation factor 5 (ARF5) upon Zika virus (ZIKV) infection in vivo were characterized by construction of gene knockout mice via CRISPR-Cas9. Firstly, ARF5 and ARF4 genes were modified by the CRISPR-Cas9 system and then microinjected into the fertilized eggs of C57BL/6JGpt mice. Fertilized eggs were transplanted to obtain ARF4 or ARF5 knockout (ARF4KO or ARF5KO) mice, and ARF4/5 double knockout mice were achieved by the mating between ARF4KO and ARF5KO mice (ARF4KO/ARF5KO). Then, the mouse genotypes were identified by PCR to identify the positive knockout mice, and RT-qPCR was employed to examine the knockout efficiency. The mice were then infected with ZIKV and the blood and tissue samples were collected after 2, 4, and 6 days. RT-qPCR was then employed to determine the virus load, and hematoxylin-eosin staining was employed to observe the pathological changes in the tissue. The results showed that expected PCR bands were detected from ARF4KO^-/+, ARF5KO^-/-, and ARF4KO^-/+/ARF5KO^-/- mice, respectively. The results of mRNA transcription measurement indicated the significant knockdown of ARF4 by 37.8%-50.0% but not ARF5 in ARF4KO^-/+ compared with the wild-type mice. Meanwhile, complete knockout of ARF5 and no changes in ARF4 were observed in ARF5KO^-/- mice. Additionally, completed knockout of ARF5 and down-regulated mRNA level of ARF4 in the lung, kidney, and testis were detected in ARF4KO^-/+/ARF5KO^-/-mice in comparison with the wild-type mice. The virus load in the serum decreased in ARF4KO^-/+ mice, while it showed no significant change in ARF5KO^-/- or ARF4KO^-/+/ARF5KO^-/- mice compared with that in the wild type. Meanwhile, ARF4KO^-/+ mice showcased no significant difference in virus load in various tissues but attenuated pathological changes in the brain and testis compared with the wild-type mice. We successfully constructed ARF4KO and ARF5KO mice by CRISPR-Cas9 in this study. ARF4 rather than ARF5 is essential for ZIKV infection in vivo. This study provided animal models for studying the roles of ARF4 and ARF5 in ZIKV infection and developing antivirals.
Animals ; ADP-Ribosylation Factors/metabolism* ; Zika Virus Infection/genetics* ; Mice ; Mice, Knockout ; Zika Virus/genetics* ; Mice, Inbred C57BL ; CRISPR-Cas Systems ; Viral Load ; Male ; Female

OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.

Ovarian Leydig cell tumor(LCT), also known as ovarian testicular stromal cell tumor, is a rare sex cord stromal tumor, accounting for about 0.1% of all ovarian tumors. LCT is often accompanied by clinical manifestations of elevated androgen, and the imaging manifestations sometimes lack specificity. The diagnosis requires histopathological examination. Surgery is the primary treatment method, and postoperative prognosis is generally favorable. This paper retrospectively analyzes the diagnosis and treatment of a patient with LCT in our hospital combining relevant literature, explore the clinical characteristics, diagnosis, and treatment progress of LCT, aiming to improve disease management.

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Objective:To improve the level of clinical diagnosis and treatment by analyzing the clinical features and relevant factors of cryptococcosis neoformans in patients with connective tissue disease(CTD).Methods:Twelve patients with CTD and cryptococcosis neoformans infection in Peking University People's Hospital from January 2010 to April 2021 were retrospectively enrolled. Clinical and laboratory data, treatment and outcome were collected and analyzed. Independent sample t-test or Rank-sum test was used. Results:The age of the patients ranged from 18 to 85 years old(mean 51 years old), all of whom were female. None of them were exposed to pigeons and their feces. Of the 12 patients, 3 patients suffered from rheumatoid arthritis, 7 patients had systemic lupus erythematosus, 1 patient was diagnosed with primary Sj?gren 's syndrome, and 1 patient was diagnosed as undifferentiated connective tissue disease. Four cases were cryptococcal meningitis, 8 were pulmonary cryptococcosis. None of the 12 patients had immunodeficiency virus infection. All 12 patients were given glucocorticoid alone or combined with immunosuppressive or biological agents. All were detected with positive cryptococcus neoformans antigen in serum; 6 got lumbar puncture, 2 cases were positive for ink stain, cerebrospinal fluid (CSF) culture were positive in 2, in whom 3 had high intracranial pressure, in which the highest one was more than 600 mmH 2O (1 mmH 2O=0.009 8 kPa); 7 cases underwent lung biopsy. Among these patients, all were positive for cryptococcosis neoformans in lung tissue pathological examination; 6 had the number of peripheral lymphocytes less than 1.0×10 9/L, and 2 were detected for the number of CD4 + T cell, which was significantly decreased. As for the initial anti-fungal drug therapy, all cases were treated with fluconazole intravenously; 2 were treated with combined amphotericin, 1 was treated with combined fluorocytosine, 1 was treated with amphotericin and fluorocytosine. Then oral flu-conazole was prescribed as sequential therapy. The whole treatmentcourse ranged from 4 to 21 months. Eleven patients were cured, and 1 was relieved. Conclusion:Patients with connective tissue disease complicated with cryptococcus neoformans infection have atypical clinical symptoms. Treatment with immunosuppressive drugs and glucocorticoids are related causes. Patients with decreased peripheral blood lymphocytes, especially CD4 + T cell, are more susceptible to infection. Early diagnosis and timely treatment are the key to improve the prognosis and cure of the disease.

In recent years, with the development of rectal cancer treatment mode, the anal preservation rate in rectal cancer patients has been gradually increased. In addition to preserving the anal shape, the preservation of anal function is also gradually valued. In this article, literature review on anal function related to radiotherapy and chemotherapy for rectal cancer patients was conducted, aiming to elaborate the evaluation criteria and research status of anal function in rectal cancer patients.

Objective:To investigate the relationship between polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 ( CDKN2 B- AS1) gene and the risk of ulcerative colitis (UC). Methods:From January 2012 to January 2021, a total of 534 UC patients diagnosed at the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University (Yuying Children′s Hospital) and during the same period 560 gender- and age-matched healthy controls were selected. Genotypes of CDKN2 B- AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) in venous blood were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression was used to analyze the difference in the distribution of CDKN2 B- AS1 gene polymorphisms between UC patients and healthy controls, as well as the influence on the clinicopathologic characteristics of UC patients. Software Haploview 4.2 was used to analyze the linkage disequilibrium and haplotype. Chi-square test was used for statistical analysis. Results:The frequencies of variant genotype (AG+ GG) and variant allele (G) of rs1063192 in UC patients were higher than those in healthy controls (32.4%, 173/534 vs. 24.8%, 139/560; 18.1%, 193/1 068 vs. 13.7%, 153/1 120), and the differences were statistically significant ( OR=1.45 and 1.40, 95% confidence interval(95% CI) 1.12 to 1.89 and 1.11 to 1.77, P=0.006 and 0.004, corrected P=0.030 and 0.020). The frequency of variant allele (G) of rs10757274 in UC patients was lower than that in healthy controls (34.7%, 371/1 068 vs. 39.5%, 442/1 120), and the difference was statistically significant ( OR=0.82, 95% CI 0.69 to 0.98, P=0.025). However, the difference was not significant after Bonferroni correction (corrected P>0.05). According to the Montreal classification, the frequency of homozygous variant genotype (GG) of rs1063192 in the patients with extensive colitis was higher than that in patients with proctitis plus left-sided colitis (6.6%, 14/211 vs. 1.9%, 6/323), and the difference was statistically significant ( OR=3.92, 95% CI 1.47 to 10.42, P=0.006, corrected P=0.030). There was linkage disequilibrium among rs10757274, rs2383207, rs10757278 and rs1333048 of CDKN2 B- AS1 gene. The frequency of haplotype GGGC in UC patients was lower than that in healthy controls (33.3%, 355.5/1 068 vs. 37.8%, 423.4/1 120), and the frequency of haplotype AGGC in UC patients was higher than that in healthy controls (6.7%, 71.7/1 068 vs. 3.6%, 40.3/1 120), and the differences were statistically significant ( χ2=4.81 and 11.16, P=0.028 and<0.001). Conclusions:The variation of rs1063192 in CDKN2 B- AS1 gene may increase the risk of UC. The risk of extensive colitis in patients carrying homozygous variant genotype (GG) of rs1063192 may rise. Among the haplotypes composed of rs10757274, rs2383207, rs10757278 and rs1333048, the risk of UC may decrease in the individuals carrying haplotype GGGC. However, the risk of UC may increase in the individuals carrying haplotype AGGC. The correlation between the variation of 10757274 and the risk of UC still needs to be further verified by expanding the sample size.

Objective:To explore the motion and influencing factors of implanted gold markers in guiding liver stereotactic body radiation therapy (SBRT) using abdominal compression.Methods:Twenty patients with oligometastatic colorectal cancer or primary hepatocellular carcinoma from January 2016 to December 2019 were included. All patients were treated with SBRT under abdominal compression, with 1-3 gold markers were implanted within 2 cm from the lesion before positioning. Four-dimensional computed tomography (4DCT) scan was used for treatment planning. The respiratory cycle was divided into 0-90% respiratory phase images based on the respiratory signal, which were reconstructed by the system (Pinnacle 3 version 9.1; Philips Medical System, Madison, WI, USA), and cone beam CT validation images before radiation exposure were obtained. The liver volume was divided into 3 parts: within 2 cm from the main hepatic portal vein, 2-5 cm from the main hepatic portal vein, and>5 cm from the main hepatic portal vein. The motion of different tumor locations was evaluated. Results:The average intrafractional motion amplitude was (2.63±2.81) mm in the cranial-caudal (CC) direction, (1.35±1.23) mm in the anterior-posterior (AP) direction, and (0.76±0.88) mm in the left-right (LR) direction, respectively. The average interfractional motion amplitude was (3.45±3.06) mm, (2.64±2.60) mm, and (2.23±2.07) mm, respectively. Both the intra-or inter-fractional motion amplitudes in the CC direction were the highest, followed by those in the AP and LR direction (all P<0.001). The motion varied at different tumor locations. The longer distance from the main hepatic portal vein, the larger the intrafractional motion (all P<0.05). To cover the 95% population-based confidence interval, the internal target volume (ITV) was suggested to include the expansion of 3.9 mm, 5.2 mm and 7.9 mm in the LR, AP and CC direction. The expansion of 4.3 mm, 4.4 mm and 6.1 mm was delivered within 2 cm from the main hepatic portal vein, and 3.5 mm, 7.3 mm and 9.7 mm>5 cm from the main hepatic portal vein, respectively. The expansion varied significantly depending on the tumor location, whereas the motion in the CC direction was the largest regardless of the tumor location. The longer distance of the tumor from the main portal vein, the larger expansion in the CC direction. The expansion of tumor > 5 cm from the main portal vein in the AP direction was larger than that of inner parts. Conclusion:Liver tumors at different locations require individual external expansion of ITV.