Objective To evaluate the long-term survival of patients with T1a-bN0M0 non-small cell lung cancer (NSCLC) after sublobar resection. Methods Patients with T1a-bN0M0 NSCLC who underwent sublobar resection from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into a segmentectomy group and a wedge resection group according to the resection method. After propensity-score matching at a ratio of 1:1, the overall survival (OS) and disease-specific survival (DSS) of patients were analyzed using Cox regression model, log-rank test, and restricted mean survival time (RMST). Results A total of 3262 patients were included in the study, including 1321 males and 1941 females, with a median age of 69.0 years. Among them, 2419 patients were in the wedge resection group and 843 patients were in the segmentectomy group. After matching, 843 pairs of patients were obtained. The results showed that the 10-year DSS rate (68.0% vs. 60.6%, P=0.011) and 10-year OS rate (40.8% vs. 37.0%, P=0.049) of the segmentectomy group were better than those of the wedge resection group, while there was no statistical difference in the 5-year DSS rate (82.9% vs. 79.5%, P=0.112) or 5-year OS rate (68.9% vs. 64.9%, P=0.096). Multivariate Cox regression analysis revealed that male gender [HR=1.54, 95%CI (1.28-1.86), P<0.001] and age [HR=1.02, 95%CI (1.01-1.03), P<0.001] were independent risk factors for DSS, while increased number of regional nodes dissected (RND) [HR=0.98, 95%CI (0.96-1.00), P=0.018] and segmentectomy [HR=0.82, 95%CI (0.68-0.98), P=0.030] served as protective factors. For OS, male gender [HR=1.54, 95%CI (1.35-1.75), P<0.001], age [HR=1.04, 95%CI (1.03-1.04), P<0.001], and histological subtypes of squamous cell carcinoma [HR=1.62, 95%CI (1.41-1.86), P<0.001] or large cell carcinoma [HR=1.64, 95%CI (1.07-2.52), P=0.023] were identified as independent risk factors, whereas increased RND was a protective factor [HR=0.98, 95%CI (0.97-0.99), P=0.002]. Surgical approach was not an independent prognostic factor for OS. Subgroup analysis showed that segmentectomy had a better 10-year OS-RMST in patients with adenocarcinoma (P=0.045), right lower lobe tumor (P=0.014), and tumor diameter ≤1.6 cm (P=0.006). Conclusion Increasing lymph node dissection during sublobar resection may improve prognosis. Compared with wedge resection, segmentectomy may improve the long-term DSS rate of patients with T1a-bN0M0 NSCLC.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.

A 41-year-old male was presented with rapidly progression memory impairment for 2 months and episodic limb shaking for 2 weeks as the main manifestations.Physical examination showed verbal disadvantage with decreased memory,attention,comprehension,and orientation.Serum vitamin B12 levels decreased,serum anti gastric parietal cell antibodies and anti-intrinsic factor antibodies were positive.Blood analysis showed macrocytic anemia,neuropsychological scale showed functional impairment in multiple cognitive domains,electrophysiological examination showed peripheral nerve damage,cerebrospinal fluid and imaging examination showed no abnormalities.The patient was diagnosed as having vitamin B12 deficiency dementia,vitamin B12 deficiency related involuntary movement and pernicious anemia.Supplementing with B vitamins and folic acid significantly improved cognitive impairment and eliminated symptoms of limb shaking.The purpose of this case report is to enhance the understanding of clinical doctors about dementia and involunting movement caused by vitamin B12 deficiency,in order to diagnose and treat it early.