The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

OBJECTIVE: To investigate the efficacy and safety of diagnostic-driven therapy for invasive fungal disease(IFD) in patients with myeloid hematologic malignancies. METHODS: A retrospective analysis was conducted on the clinical data of 91 patients with myeloid hematologic malignancies who received diagnostic-driven therapy for IFD at the Second Hospital of Anhui Medical University from January 1, 2020 to December 31, 2023. The patients were divided into two groups based on medication: 44 patients in the caspofungin group and 47 patients in the voriconazole group. The clinical efficacy and adverse reactions of the two groups were compared and analyzed. RESULTS: The overall response rates in the caspofungin and voriconazole groups were 67.4% and 60.0%, respectively. Among patients who transitioned to diagnostic-driven therapy following prophylactic or empirical treatment with triazole antifungal agents, the response rate of the caspofungin group was significantly higher than that of the voriconazole group (76.9% vs 35.3%, P <0.05). A total of 9 patients in both groups experienced adverse reactions, and no grade III or higher adverse reactions occurred. The incidence of grade I-II adverse reactions in the caspofungin group was lower than in the voriconazole group (2.3% vs 17.0%, P <0.05). CONCLUSION In patients with myeloid hematologic malignancies, caspofungin and voriconazole demonstrate comparable clinical efficacy in diagnostic-driven therapy for IFD, but caspofungin is associated with a lower incidence of adverse reactions. Caspofungin exhibits significant effectiveness when initiating diagnostic-driven therapy after prophylactic or empirical treatment with broad-spectrum triazole antifungal agents.
Humans ; Retrospective Studies ; Hematologic Neoplasms/complications* ; Antifungal Agents/therapeutic use* ; Voriconazole/therapeutic use* ; Caspofungin/therapeutic use* ; Invasive Fungal Infections/diagnosis* ; Male ; Female ; Mycoses/drug therapy* ; Middle Aged ; Treatment Outcome ; Aged ; Adult

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P＜0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P＜0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P＜0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P＜0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective To establish a high performance liquid chromatography(HPLC)characteristic chromatogram and multi-component content determination method for the substance benchmark of Fuzi Decoction.Methods The characteristic chromatogram method of Fuzi Decoction substance benchmark was established,and the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition)was used to analyze the characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples.The HPLC content determination methods of 1 1 components in the Fuzi Decoction substance benchmark samples were established respectively,and the dry extract rate of 15 batches of Fuzi Decoction substance benchmark samples was determined.Results The similarity of characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples was greater than 0.9,and 12 common peaks were selected and eight of them were identified.The results showed that the contents of benzoylmesaconine,benzoylhypaconine,atractylenolide Ⅲ,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,gallic acid,albiflorin,paeoniflorin,1,2,3,4,6-penta-galloyl glucose and benzoyl paeoniflorin were 0.050 3-0.191 1,0.026 7-0.047 0,0.043 0-0.127 6,0.554 6-1.006 8,0.568 7-0.979 5,0.929 9-1.726 1,1.058 9-2.118 4,1.430 3-4.965 5,6.882 9-9.511 1,0.056 1-0.262 5,0.160 6-0.369 0 mg/g,respectively.The average dry extract rate of the 15 batches of Fuzi Decoction substance benchmark samples was 29.54％.Conclusion The established characteristic chromatogram and multi-index content determination method are accurate and stable,which provides a basis for the quality control of the substance benchmark and related preparations of Fuzi Decoction.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.