OBJECTIVE: To explore the prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP-1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long-acting GLP-1RA seem to exert a greater effect in increasing heart rate, and the effect is dose-dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP-1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP-1RA in clinical practice, especially in patients with high-risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP-1RA and symptomatic intervention should be given if necessary.

Objective:To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).Methods:Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.Results:A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.Conclusions:SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP-1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long-acting GLP-1RA seem to exert a greater effect in increasing heart rate, and the effect is dose-dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP-1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP-1RA in clinical practice, especially in patients with high-risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP-1RA and symptomatic intervention should be given if necessary.

Objective:To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).Methods:Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.Results:A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.Conclusions:SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective:To learn about the epidemiological and clinical characteristics of human brucellosis in Shaanxi Province, and to provide reference for brucellosis prevention and control.Methods:Through the China Disease Control and Prevention Information System and the Shaanxi Provincial Brucellosis Prevention and Control Work System, report data and case investigation data on human brucellosis cases in Shaanxi Province from 2020 to 2022 were collected, respectively, and the epidemiological characteristics, exposure history and clinical manifestations of the cases were analyzed descriptively.Results:A total of 4 240 human cases of brucellosis were reported in Shaanxi Province from 2020 to 2022, with no death. The average annual incidence was 3.60/100 000, with an average growth rate of 22.33%. Cases of brucellosis were reported from January to December throughout the year, mainly from April to August, accounting for 63.40% (2 688/4 240). Cases of brucellosis were reported in 12 prefectures (including Yangling District and prefecture-level administrative divisions directly administered by the province) and 90 counties (districts and cities), accounting for 79.65% (90/113) of the total number of counties (districts and cities). The male to female ratio of the cases was 2.92 ∶ 1.00 (3 159 ∶ 1 081). The onset age was mainly from 30 to 74 years old, accounting for 89.81% (3 808/4 240). Farmer was the main occupation, accounting for 87.12% (3 694/4 240). A total of 4 223 cases were investigated in Shaanxi Province from 2020 to 2022, with the acute phase being the main stage of disease progression, accounting for 94.67% (3 998/4 223); hospitalized cases accounted for 59.79% (2 525/4 223); the main risk occupations of brucellosis were rearing and grazing, accounting for 78.43% (3 312/4 223). The main exposure routes were direct contact through skin and mucous membranes and respiratory infection, accounting for 95.07% (4 015/4 223). There were 4 015 cases with a history of contact with livestock and their products, with sheep being the main type of contact (accounting for 96.91%, 3 891/4 015), and the possible infection sites were mainly at home (58.53%, 2 350/4 015). The main clinical symptoms were fever, muscle and joint pain, fatigue and excessive sweating, accounting for 75.49% (3 188/4 223), 58.23% (2 463/4 223), 68.17% (2 879/4 223) and 63.65% (2 688/4 223), respectively. A total of 139 Brucella strains were isolated and cultured, with sheep type 3 being the main bacterial type, accounting for 75.54% (105/139). Conclusions:The epidemic of brucellosis in Shaanxi Province is showing a clear upward trend, and the scope of the epidemic is becoming wider and wider. The incidence of brucellosis is mainly in free-range households, and the course of the disease is mostly in the acute phase. Brucellosis is mainly caused through direct contact with the skin and mucous membranes and respiratory infections. The clinical manifestations are diverse but non-specific. It is necessary to effectively improve the personal protection awareness and level of high-risk groups to reduce the occurrence of brucellosis.

ObjectiveTo investigate the effects of Yanghetang （YHT） on breast cancer 4T1 cells and their mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodThe YHT-containing serum was prepared from SD rats. The rats were randomly assigned into a blank group （normal saline） and low-， medium-， and high-dose （5.8， 11.6， 23.2 g·kg^-1， respectively） YHT groups. The serum containing 10% YHT in each group was mixed with 90% RMPI 1640 complete medium， and the mixture was used to interfere with the cells. Cell counting kit-8 （CCK-8） method was used to detect the proliferation of the 4T1 cells treated with YHT for 24， 48， 72 h. The apoptosis， migration， and invasion of 4T1 cells were detected by flow cytometry， scratch test， and Transwell assay， respectively. Western blot was employed to determine the expression levels of MEK1/2， phosphorylation （p）-MEK1/2， ERK1/2， p-ERK1/2， and rat sarcoma virus （RAS） protein. ResultCompared with the blank group， the intervention with YHT-containing serum for 24， 48， and 72 h had significant inhibitory effect on 4T1 cell proliferation （P<0.05， P<0.01）. After intervention with YHT-containing serum for 48 h， the apoptosis rate of cells increased （P<0.01）. Compared with the blank group， the intervention with YHT for 24 h and 48 h decreased the healing ability of cells in the scratch test （P<0.01）. The invasive ability of cells treated with the low， medium， and high-dose YHT containing serum showed a decreasing trend （P<0.01）. Compared with the blank group， YHT-containing serum did not change the expression of MEK1/2 and ERK1/2 while down-regulating the expression of p-MEK1/2， p-ERK1/2， and RAS protein （P<0.01）. ConclusionYHT can inhibit the proliferation， migration， and invasion and promote the apoptosis of breast cancer 4T1 cells. In may promote the apoptosis by inhibiting the MEK/ERK signaling pathway and down-regulating the expression of p-MEK1/2， p-ERK1/2， and RAS protein.

Objective To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on angiogenesis and functional recovery after focal cerebral ischemia in rats.Methods BMSCs were isolated and cultured using the whole bone marrow adherent method,and conducted phenotypic identification using flow cytometry analysis of surface positive antigen of CD29,CD90 and the negative antigen of CD34,CD45.Rats were subjected to middle cerebral artery occlusion (MCAO) for 90 minutes,and divided into three groups randomly,the sham group,model group and BMSCs group.24 hours after cerebral ischemia,rats were injected with 1 ml BMSCs solution (1 × 106 cells/ml) or PBS via the tail vein.The modified neurological severity score(mNSS) test,the corner test and the adhesive tape test were used to evaluate sensorimotor function on the 1,7,14 and 28 days after ischemia.Infarcted volume was detected by toluidine blue staining,and the numbers of vWF positive microvessels and vascular endothelial growth factor (VEGF) positive cells in the ischemic boundary were determined by immunofluorescence.Results By flow cytometric analysis,the cell phenotype of passage 3 BMSCs showed that CD29,CD90,CD34 and CD45 were 98.3％,97.4％,0.2％ and 4.8％,respectively.Compared with the model group,BMSCs significantly reduced the score of mNSS(P＜0.01),the number of right turn of corner test(P＜0.05),latency of removal adhesive tape(P＜0.05) and the infarcted volume (P＜0.01).The numbers of vWF positive vesscls and the VEGF positive cells were (42.97±8.64)/mm2 and (54.83± 10.66)/mm2 at the boundary zone in model group 14 days after ischemia,respectively.BMSCs significantly increased the numbers of vWF positive vessels ((69.43± 7.29)/mm2) and VEGF positive cells ((78.70±6.16)/mm2,P＜0.01).Conclusion BMSCs can improve the functions of cerebral lesions after cerebral ischemia,which may be associated with the enhanced angiogenesis and VEGF expression in the ischemic boundary.