To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

OBJECTIVE To optimize the forming process of Kaixin granules and establish its physical fingerprint.METHODS Using particle forming rate， hygroscopicity rate， dissolution rate， and angle of repose as indices， the key process parameters of the granule forming process were determined by Plackett-Burman design. The analytic hierarchy process （AHP） combined with the entropy weight method was used to comprehensively weight the indices， and the forming process of Kaixin granules was optimized and validated by Box-Behnken response surface methodology. A physical fingerprint of Kaixin granules was established based on the following physical indices： angle of repose， Hausner ratio， bulk density， tapped density， moisture content， hygroscopicity ratio， and relative uniformity index， with similarity evaluation was performed. Cluster analysis and partial least squares discriminant analysis （PLS-DA） were performed using SPSS 20.0 and the SPSSPRO online analysis platform， respectively.RESULTS The key process parameters were ethanol volume fraction， ethanol amount， and the drug-excipient ratio. The optimal forming conditions were as follows： ethanol volume fraction of 87%， ethanol amount of 27%， and a drug-excipient ratio of 1∶1. Validation showed that the average comprehensive scores of three batches were 97.82， with an RSD of 0.19%. The similarity of the physical fingerprints of ten batches of Kaixin granules prepared under the optimal forming process were greater than 0.98. The results of cluster analysis showed that the ten batches were divided into two groups： S4， S5， S7， S8 and S10 in one cluster， and S1-S3， S6 and S9 in another. The variable importance in projection values of Hausner ratio， relative uniformity index， bulk density， and moisture content were greater than 1.CONCLUSIONS The optimized forming process is stable and feasible. The established physical fingerprint can effectively characterize the overall physical properties of Kaixin granules. Hausner ratio， relative uniformity index， bulk density， and moisture content are the key physical indices.

Objective:To report the clinical, imaging, and pathological features of a case of MYH7 gene-related scapuloperoneal myosin storage myopathy. Methods:Clinical data were collected from a patient with MYH7 gene-related scapuloperoneal myosin storage myopathy who presented to Peking University First Hospital in February 2025. The patient was evaluated with muscle magnetic resonance imaging, muscle biopsy, and whole-exome sequencing. Results:The patient was a 52-year-old female, with a 12-year history of progressive difficulty in foot dorsiflexion, exercise-induced fatigue, and lower limb pain. Over the past 3 years, she developed proximal upper limb weakness and post-exertional myalgia. Physical examination revealed scapuloperoneal weakness distribution accompanied by sensorineural hearing loss. Electromyography demonstrated myogenic changes in the deltoid and tibialis anterior muscles. Serum creatine kinase levels were within normal limits. Lower limb magnetic resonance imaging showed mild atrophy of the thigh muscles and significant fatty infiltration in the tibialis anterior, extensor hallucis longus, and extensor digitorum longus. Tibialis anterior muscle biopsy revealed dystrophic-like changes with sub-sarcolemmal hyaline bodies containing abundant granulofilamentous material. Whole exome sequencing identified a heterozygous pathogenic variant of c.5352_5354del(p.K1784del) in the MYH7 gene. Conclusions:This patient is the first reported one in China with MYH7 gene-related scapuloperoneal myosin storage myopathy, exhibiting characteristic scapuloperoneal weakness, selective fatty infiltration of the anterior lower leg muscles on imaging and sub-sarcolemmal hyaline body pathological changes. The diagnosis of this disease relies on characteristic pathological findings and genetic test results.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome.METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),and caspase-1 precursor (pro-caspase-1) were predicted by molecular docking.Sixty 1-day-old pregnant rats were randomly divided into normal group,model group,dexamethasone group (0.002 g/kg),and Pangshi antai zhixue decoction low-,medium-,and high-dose groups (11.025,22.05,44.10 g/kg),with 10 rats in each group.Each group was given distilled water/corresponding medicinal solution intragastrically,once a day,for 12 consecutive days.Except for normal group,other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome.24 h after the last medication,serum levels of triiodothyronine (T3),thyroxine (T4),interleukin-2 (IL-2),IL-4,IL-6,IL-10,and interferon-γ (IFN-γ) were all detected;the abortion rate and uterine coefficient were calculated;the pathological morphology of the pregnant uterus was observed;protein expressions of NLRP3,ASC and caspase-1 were detected.RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3,ASC,and pro-caspase-1 were all less than-5 kJ/moL.The animal experiment results showed that compared with normal group,the uterine coefficient and serum levels of IL-4,IL-6 and IL-10 were decreased significantly in model group (P<0.05);the abortion rate and serum levels of T3,T4,IL-2 and IFN-γ as well as protein expressions of NLRP3,ASC and caspase-1 were increased significantly (P<0.05);there were abortion lesions in the pregnant endometrium.Compared with the model group,most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05),and the endometrial miscarriage lesions in pregnancy were improved to varying degrees.CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome,down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2,and up-regulating anti-inflammatory cytokines such as IL-4,IL-6 and IL-10,thereby improving spontaneous abortion with heat syndrome.