In order to understand the status quo of ethical review of clinical research on the defecation function of patients with rectal cancer after sphincter-preserving surgery, analyze its causes and put forward corresponding suggestions, to arouse researchers’ attention to ethical review in subsequent relevant clinical studies. The ethical review of literatures related to the defecation function of patients with rectal cancer after sphincter-preserving surgery published on CNKI in recent 10 years was sorted out and summarized. The results showed that the ethical review of clinical research papers on defecation function of patients with rectal cancer after sphincter-preserving surgery was not optimistic. We should strengthen the ethical training of researchers, improve the ethical awareness of researchers, strictly implement the ethical norms of paper publication, strengthen the ethical requirements of manuscript contracts, perfect the ethical review system, and pay attention to the examination and supervision of informed consent, so as to promote the construction of ethical examination and approval norms of clinical research documents.

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Objective To establish and validate a method for the detection of isavuconazole in human plasma by ultra-performance liquid chromatography-mass spectrometry,and apply to blood concentration monitoring to optimize drug treatment regimens.Methods The proteins in plasma samples were precipitated with acetonitrile;isavuconazole-D4 was used as the internal standard.Chromatographic column was ACQUITY UPLC BEH C18(2.1 mm × 50 mnm,1.7 μm),flow phase was 2 mmol·L-1 ammonium acetate-water(containing 0.1％formic acid,A),acetonitrile(containing 0.1％formic acid,B),flow rate was 0.2 mL·min-1,and the column temperature was 40 ℃.Injection volume was 1 μL.The ion pairs were quantitatively analyzed by electro-spray ionization positive ion mode and multiple reaction monitoring,m/z 438.30 → 224.15(isavuconazole),m/z 442.10 → 224.10(isavuconazole-D4).Results The linear range of isavuconazole was 0.31 to 40.00 μg·mL-1(R2=0.999 4);lower limit of quantification(LLOQ)was 0.31 μg·mL-1.The intra-day and inter-day precision ranged from 2.03％to 12.97％and 4.32％to 9.63％,the accuracy deviation ranged from 89.82％to 110.72％and 95.45％to 100.13％,the extraction recovery rates of low,medium and high concentrations ranged from 94.31％to 100.23％.The results of the blood concentrations of 14 patients with clinical use of isavuconazole measured by this method showed that all patients achieved the effective therapeutic concentration of isavuconazole(＞1-2 μg·mL-1).Conclusion This method is fast,sensitive,accurate and stable,It is suitable for detecting the blood concentration of clinical isavuconazole and providing technical guidance for the adjustment of treatment regimen.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective To investigate the effectiveness and safety of endoscopic mucosal resection with precutting(EMR-P)for the treatment of rectal neuroendocrine neoplasm(RNEN)smaller than 1 cm in diameter.Methods Clinical data of 177 patients with RNEN smaller than 1 cm in diameter from December 2016 to December 2021 were retrospectively analyzed.According to different treatment protocols,177 patients with RNEN were divided into endoscopic mucosal resection(EMR)group(n = 46),EMR-P group(n = 40)and endoscopic submucosal dissection(ESD)group(n = 91).The en bloc resection rate,complete resection rate,operation time,postoperative hospitalization time and incidence of operative complications among the three groups were compared.Results The complete resection rate in the EMR-P group(95.0%)and ESD group(97.8%)were significantly higher than that in the EMR group(87.0%)(P<0.05);The operation time in the EMR-P group(9.86±2.23)min was longer than that in the EMR group(4.12±0.88)min,EMR-P group and EMR group were shorter than that in the ESD group(19.55±3.67)min,the difference was statistically significant(P<0.05);Postoperative hospitalization time in the EMR group was(2.45±0.29)d and EMR-P group was(2.43±0.23)d,which were shorter than that in the ESD group(3.30±0.32)d,and the difference was statistically significant(P<0.05).There were no significant difference in the rates of en bloc resection and operative complications among the three groups(P>0.05).Conclusion EMR-P for the treatment of RNEN<1 cm in diameter has the advantages,such as simple operation,short operation time and hospitalization time,high histological complete resection rate and low complication rate,which is worthy of clinical application.

Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency. MethodForty male SPF-grade rats were randomly assigned into five groups： blank control， model， low- （3.51 g·kg^-1） and high-dose （7.02 g·kg^-1） Sishenwan， and Peifikang （0.54 g·kg^-1） groups. Except the blank control group， the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions， the general conditions of the rats were observed， and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex （AWR） were measured. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of tumor necrosis factor （TNF）-α， gastrin （GAS）， corticosterone （CORT）， and adrenocorticotropic hormone （ACTH）. Hematoxylin-eosin （HE） staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase （MAPK）， c-Jun N-terminal kinase （JNK）， transient receptor potential vanilloid 1 （TRPV1）， and protease-activated receptor 2 （PAR2） in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue， and immunofluorescence was used to detect the positive expression of substance P （SP） and calcitonin gene-related peptide （CGRP） in the colon tissue. ResultCompared with the blank control group， the model group showed increased number of defecation pellets within 6 h （P<0.01）， decreased minimum threshold of AWR （P<0.01）， elevated serum TNF-α level （P<0.01）， lowered levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， increased mast cell degranulation rate （P<0.01）， increased positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and upregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.01）. Compared with the model group， the high-dose Sishenwan group showed increased minimum threshold of AWR （P<0.01）， reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups （P<0.05， P<0.01）， lowered TNF-α level （P<0.05， P<0.01）， elevated levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， decreased mast cell degranulation rate （P<0.01）， reduced positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and downregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.05， P<0.01）. ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.

Tablets represent the most widely used oral solid dosage form in the pharmaceutical industry. Puerarin monohydrate (PUEM), a solid form of the natural antihypertensive drug puerarin, is commercially available. However, the low solubility of PUEM poses a significant challenge for the development of its tablet dosage form. In this study, we successfully prepared the sodium chelates of puerarin (PUE-Na·7H₂O) using reactive crystallization techniques. The crystal structure of PUE-Na·7H₂O was analyzed using single crystal technology, which revealed the structural characteristics of its metal chelate. Our thermodynamic studies demonstrated that the formation of PUE-Na·7H₂O involved the simultaneous deprotonation of PUE and the chelation of PUE^- and Na⁺. This reaction process was spontaneous and exothermic (ΔG < 0, ΔH < 0), and reducing the temperature facilitated the formation of the chelate. Nucleation kinetics studies revealed that chelate molecules were more likely to nucleate and crystallize under low temperature, high concentration, and high rotational speed conditions. Compared to commercially available PUEM, PUE-Na·7H₂O showed significantly improved water solubility, with a 33.5-fold increase in solubility and a 37.6-fold decrease in intrinsic dissolution rate. Our study identified drug-sodium chelation as an effective means for improving drug solubility and elucidated the mechanisms governing its formation kinetics and thermodynamics. These findings could provide new solutions for related product development and tremendous commercial opportunities.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.