Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation

OBJECTIVE: To investigate the effect of piperlongumine(PL) on the proliferation and ferroptosis of human adriamycin-resistant chronic myeloid leukemia K562/ADR cells, and to explore its possible molecular mechanism. METHODS: CCK-8 assay was used to detect the effect of PL on the survival rate of K562/ADR cells and to screen the appropriate drug concentration. After K562/ADR cells were treated with low, medium and high concentrations of PL(2, 4, and 6 μmol/L), EdU proliferation assay and plate colony formation assay were used to detect cell proliferation and colony formation ability. CCK-8 assay was used to detect the effects of different inhibitors (Fer-1, Z-VAD, Nec-1) combined with PL on cell proliferation. The intracellular Fe²⁺, ROS, malondialdehyde(MDA) and glutathine(GSH) contents were respectively detected by iron ion colorimetry, DCFH-DA fluorescent probe, MDA and GSH kits. RT-qPCR and Western blot were respectively used to detect the expression level of GPX4 mRNA and protein in cells. Bioinformatics websites predicted miRNA that could target and regulate GPX4 . RT-qPCR was used to detect the effects of different concentrations of PL on the expression levels of the predicted miRNA. Dual luciferase gene reporter assay was used to verify the targeting relationship between miR-214-3p and GPX4 . After treating cells with PL or PL+miR-214-3p inhibitor, the Fe²⁺, ROS, MDA, GSH centents and GPX4 protein expression levels in cells were detected. RESULTS: PL inhibited K562/ADR cell proliferation in a concentration-dependent manner（r =0.979）. Compared with the blank control group, the survival rate, EdU positive cells rate in low, medium and high concentration PL groups were significantly decreased (P < 0.01). Compared with the PL group alone, the survival rate of cells in the Z-VAD+PL group was increased slightly (P < 0.05). The cell survival rate was significantly increased in medium or high concentration PL+Fer-1 group (P < 0.01). Compared with blank control group, ROS expression level in low concentration PL group was slightly increased (P < 0.05), and GSH content was slightly decreased (P < 0.05). In medium and high concentration PL groups, the contents of Fe²⁺, ROS and MDA were significantly increased (P < 0.01), while the contents of GSH, expression of GPX4 mRNA and protein were significantly decreased(P < 0.01). Bioinformatics prediction and double luciferase reporter gene experiment confirmed the targeting relationship between GPX4 and miR-214-3p. Compared with the blank control group, the expression level of miR-214-3p in cells of medium and high concentration PL groups was significantly increased (P < 0.01). Compared with PL group alone, the intracellular Fe²⁺, ROS and MDA contents in PL+miR-214-3p inhibitor group were all decreased (P < 0.01), while GSH content and GPX4 protein expression levels were significantly increased (P < 0.01). CONCLUSION Medium and high concentrations of PL can inhibit the proliferation of K562/ADR cells by inducing ferroptosis, which is related to the regulation of miR-214-3p pathway.
Humans ; Ferroptosis/drug effects* ; MicroRNAs/metabolism* ; Dioxolanes/pharmacology* ; Cell Proliferation/drug effects* ; K562 Cells ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Reactive Oxygen Species ; Doxorubicin/pharmacology* ; Signal Transduction ; Piperidones

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the internalized weight bias and weight control beliefs regarding the current status,influencing factors,and impacts on eating behaviors of women losing weight. Methods A convenient sampling method was used to select the females who underwent physical examination in the Peking Union Medical College Hospital from August to December 2023.The general information questionnaire,Weight Bias Internalization Scale,Weight Control Belief Questionnaire,and Chinese version of Three-Factor Eating Questionnaire were utilized for investigation.Latent class analysis was conducted to explore the potential categories based on the characteristics of internalized weight bias and weight control beliefs.Univariate analysis and multiple-factor linear regression analysis were performed to explore influencing factors of potential categories and their effects on eating behaviors. Results A total of 518 subjects were included in this study.The internalized weight bias and weight control beliefs could be classified into three potential categories: low weight bias tolerance type(53.7%),medium weight bias persistence type(29.5%),and high weight bias overcritical type(16.8%).Logistic regression analysis showed that body mass index,unmarriage,and divorce were the influencing factors of the high weight bias overcritical type.The scores of non-control eating and emotional eating in medium weight bias persistence type and high weight bias overcritical type were higher than those in low weight bias tolerance type(all P<0.001). Conclusions The attitudes of Chinese women towards body weight can be categorized into low weight bias tolerance type,medium weight bias persistence type,and high weight bias overcritical type.The high weight bias overcritical type is characterized by high weight bias and high personal responsibility attribution,and it is closely associated with negative eating behaviors.A high body mass index,unmarriage,and divorce are high-risk factors for developing the high weight bias overcritical type.
Humans ; Female ; Feeding Behavior/psychology* ; Surveys and Questionnaires ; Adult ; Body Mass Index ; Weight Loss ; Body Weight ; Body Image ; Middle Aged ; Weight Prejudice

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

OBJECTIVE To explore the effect of Xuanbai Chengqi Decoction on respiratory and oxygenation functions and the ex-pression levels of serum aquaporin(AQP)1 and AQP5 in patients with severe pneumonia complicated with gastrointestinal dysfunction of lung heat and fu-organ repletion type.METHODS 60 patients with severe pneumonia complicated with gastrointestinal dysfunc-tion of lung heat and fu-organ repletion type were randomly divided into control group and treatment group,with 30 cases each.The control group received standardized Western medicine treatment,and the treatment group was treated with Xuanbai Chengqi Decoction in addition to the control group.Both groups were treated for 7 d.The respiratory rate and oxygenation index,mechanical ventilation u-tilization rate,the clinical score including CURB-65 and CPIS scores,TCM syndrome score,gastrointestinal function indicators inclu-ding intra-abdominal pressure,serum gastrin(GAS)and vasoactive intestinal peptide(VIP),AQP1 and AQP5 levels were compared between the two groups before and after treatment.Ventilation utilization and ICU hospitalization days during treatment were compared between the two groups.RESULTS After treatment,compared with the control group,the respiratory rate,TCM syndrome score and intra-abdominal pressure in the treatment group were decreased significantly(P<0.05,P<0.01);meanwhile,the oxygenation index and the levels of serum GAS,AQP1 and AQP5 were increased significantly(P<0.05,P<0.01).CONCLUSION Xuanbai Chengqi Decoction can significantly improve clinical symptoms such as respiratory and oxygenation functions in patients,and its mechanism may be related to the regulation of AQP1 and AQP5.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

ObjectiveTo analyze the relationship between somatic symptoms， five-state personality and emotional symptoms of bipolar disorder （BD）， and to provide a reference for the clinical diagnosis and treatment of BD. MethodsThe basic information of the BD patients was collected， and the self-administered somatic symptom questionnaire was used to investigate the somatic symptoms with a frequency of ＞20%， which were scored as the somatic symptom scores； the 24-item Hamilton Depression Scale （HAMD） was used to evaluate the patients' depressive symptoms， the Young Mania Rating Scale （YMRS） was used to evaluate the patients' manic symptoms， the Hamilton Anxiety Scale （HAMA） was used to evaluate the patients' anxiety symptoms， and Five-State Personality Test was used to evaluate the patients' five-state personality （including taiyang personality， shaoyang personality， yin-yang balance personality， shaoyin personality， and taiyin personality）. Network analysis and linear regression were used to analyse the correlation between the somatic symptom scores and the five-state personality scores， HAMD scores， YMRS scores， and HAMA scores. ResultsThere were 269 patients with BD included， and 19 somatic symptoms with a frequency of ＞20%， the top three being lack of strength （152 cases， 56.51%）， dry mouth （137 cases， 50.93%）， and preference for cold drinks （112 cases， 41.64%）， and the somatic symptom scores were ［7.0 （0，10.0）］ points； the YMRS scores were ［3.0 （0， 7.5）］ points； the HAMD scores were ［11.0 （5.0， 18.0）］ points； and HAMA score was ［6.0 （2.0， 10.0）］ points. Among the five-state personalities， taiyang personality ［10.0 （7.0， 13.0）］ score； shaoyang personality ［10.0 （7.5， 13.0）］ score； yin-yang balance personality ［5.0 （3.0， 7.0）］ score； shaoyin personality ［13.0 （10.0， 16.0）］ score； and taiyin personality ［14.0 （9.0， 18.0）］ score. Complex network analysis showed that BD somatic symptoms were positively correlated with taiyin personality score （r = 0.23）， HAMD score （r = 0.21）， and YMRS score （r = 0.13）； taiyin personality score was positively correlated with HAMD score （r = 0.17） and negatively correlated with YMRS score （r = -0.03）. Linear regression analyses showed that somatic symptom scores were positively correlated with HAMD score （β = 0.138， P = 0.003）， YMRS score （β = 0.128， P = 0.006）， and taiyin personality scores （β = 0.182， P＜0.001）. ConclusionDepression， mania， and taiyin personality are independent risk factors for somatic symptoms in patients with BD， and taiyin personality is strongly associated with somatic symptoms in patients with BD.

Objective To analyze the diagnostic quality of imported malaria in Hubei Province from 2019 to 2022, and to further improve the diagnostic level and consolidate the achievements in eliminating malaria. Methods The samples of reported malaria cases in Hubei were collected by the provincial reference laboratory (PRL) from 2019 to 2022. The microscopy and fluorescent PCR were performed to confirm the infection of plasmodium species of each case．The positive coincidence rate and species coincidence rate were analyzed and compared． Results A total of 257 imported malaria cases were reported in Hubei Province from 2019 to 2022. Among 229 malaria cases were confirmed, the overall coincidence for malaria diagnosis was 91.24% (229/251), and the overall coincidence rate for parasite species identification was 86.03% (197/229). The difference in species coincidence rate among different years was statistically significant (χ²=10.458, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification in different cities (prefectures) of Hubei Province were 71.43% to 100.00% and 50.00% to 100.00%, respectively, with significant differences among different regions (χ²=29.283, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification were 72.73% to 100.00% and 0.00% to 100.00% in different diagnostic institutions, and the coincidence rate of species identification in hospitals (87.61%) was higher than that in Centers for Disease Control institutions (54.55%) (χ²=81.275, P<0.05). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale identification were 91.50%, 88.57%, 80.00%, and 58.06%, respectively (χ²=19.777, P<0.05). Conclusion The quality of the qualitative diagnosis of malaria cases reported online from 2019 to 2022 is generally high. However, the ability of Plasmodium typing needs to be improved. In the future, technical training and quality control should be strengthened to improve the malaria surveillance capability during the post-elimination stage.

A rapid analytical method for simultaneous determination of 32 kinds of multi-residue veterinary drugs in eggs was developed using a modified QuEChERS technique based on a reduced graphene oxide-coated melamine sponge(r-GO@MeS)by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The influences of graphene oxide(GO)concentrations,sponge dosages,and purification modes on drug recoveries were investigated during the purification process.The optimal purification conditions involved using a GO concentration of 0.5 mg/mL,a sponge dosage of 6.0 cm3/mL,and a dynamic purification mode of 5 extrusion cycles.Separation was achieved using an Agilent Eclipse Plus C18 RRHD column(100 mm×2.1 mm,1.8 μm),and quantitative analysis was performed by the external standard method using an electrospray ionization source(ESI)in multiple reaction monitoring(MRM)mode.The results showed that all 32 kinds of veterinary drugs exhibited good linear correlation with coefficients greater than 0.999,and matrix effects(MEs)ranging from?7.8%to 18.9%.The limits of detection(LODs)and quantification(LOQs)ranged from 0.2 to 10.2 μg/kg and from 0.6 to 28.0 μg/kg,respectively.The recoveries for the three spiked levels were in the range of 66.5%?117.5%,with intra-day and inter-day precision(Relative standard deviation)below 13.3%and 16.3%,respectively.The synthetic r-GO@MeS exhibited efficient matrix purification without the need of high-speed centrifugation or strong magnetic field assistance.This significantly shorted the sample pretreatment time and improved the convenience of the matrix purification process.Combined with UPLC-MS/MS,the method was suitable for the rapid determination of multi-residue veterinary drugs in eggs.