ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η²_p = 0.641) and time (F = 230.870, P < 0.001, η²_p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η²_p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η²_p = 0.415) and time (F = 89.464, P < 0.001, η²_p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η²_p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η²_p = 0.283) and time (F = 49.650, P < 0.001, η²_p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η²_p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective:To evaluate the clinical performance of high-risk human papillomavirus (HR-HPV) genotyping in cervical cancer screening.Methods:Between June and July 2017, a prospective cervical cancer screening cohort was established in Xiaye Town, Jiyuan City, Henan Province, China by recruiting 3 254 women aged 21 to 64 years. At baseline screening, cervical exfoliated cell specimens were collected for HR-HPV genotyping and liquid-based cytology testing. Follow-ups were conducted over a 3-year period, with cytology testing in the first and second years and both HR-HPV genotyping and cytology testing in the third year. Women meeting the referral criteria were referred for colposcopy, with cervical biopsy and histopathological diagnosis performed as necessary. The endpoint was defined as cervical intraepithelial neoplasia grade 2 (CIN2) or higher confirmed by histopathological diagnosis. The sensitivity and specificity for detecting CIN2 or higher lesions of HR-HPV genotyping were calculated, as well as the cumulative risk of developing CIN2 or higher lesions over the 4-year study period in women with different baseline HR-HPV genotyping results.Results:A total of 2 741 women were included in the statistical analysis. Baseline HR-HPV genotyping detected 453 HR-HPV positive cases (16.53%), including 98 HPV 16/18 positive cases (3.58%) and 355 other HR-HPV positive cases (12.95%). During the 4-year period, 83 cases of CIN2 or higher were diagnosed. The sensitivity and specificity of baseline HR-HPV positivity for CIN2 or higher were 89.16% (95% CI: 80.66%-94.19%) and 85.74% (95% CI: 84.36%-87.02%), respectively. The corresponding rates for HPV 16/18 positivity were 43.37% (95% CI: 33.24%-54.09%) and 97.67% (95% CI: 97.02%-98.18%). The 4-year cumulative absolute risk of CIN2 or higher was highest in the HPV 16/18 positive group (36.73%, 95% CI: 27.85%-46.62%), followed by other HR-HPV positive groups (10.70%, 95% CI: 7.87%-14.38%), and the HR-HPV negative group was the lowest (0.39%, 95% CI: 0.19%-0.76%). Conclusions:HR-HPV genotyping testing exhibits high sensitivity and specificity for detecting CIN2 or higher lesions in cervical cancer screening. It also provides a scientific basis for stratifying the individual risk of developing CIN2 or higher lesions to guide subsequent management. Therefore, the HR-HPV genotyping testing can be considered as an effective method for cervical cancer screening.

[Purpose]To analyze the incidence and mortality rates of female breast cancer in Henan Province in 2020 and the trends from 2010 to 2020.[Methods]Breast cancer incidence and mor-tality data stratified by urban and rural areas and age groups were collected from Henan Provincial tumor registry,and the province's household population statistics were used.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),cumulative rate(0～74 year old)were calculated.The annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated using Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2020.[Results]In 2020,24 744 new cases and 4 989 deaths of female breast cancer were documented in Henan Province,with a crude incidence rate of 46.96/105,ASIRC of 38.43/105 and ASIRW of 35.71/105;a crude mortality rate of 9.47/105,ASMRC of 6.80/105 and ASMRW of 6.72/105,respectively.The above indicators in urban areas were signifi-cantly higher than those in rural areas.The highest incidence was observed in the age group of 50～54 years old,while the highest mortality reached in the age group of 85 years old and above.From 2010 to 2020,the overall incidence of female breast cancer showed a slow upward trend(AAPC=2.09％,95％CI:0.62％～3.58％,P=0.010),while the mortality rate exhibited a signif-icant downward trend(AAPC=-3.49％,95％CI:-5.62％～-1.30％,P=0.005).[Conclusion]The incidence and mortality rates of female breast cancer in Henan Province are still at a high level,and corresponding preventive measures and control strategies are needed to effectively reduce the health hazards of breast cancer to women.

[Purpose]To analyze the cancer incidence and mortality in 2020 and trends from 2010 to 2020 in Henan Province.[Methods]Data from cancer registries in Henan Province from 2010 to 2020 were collected and evaluated.Incidence and mortality rates were calculated by urban/rural areas,sex and age,and the incidence and mortality of cancers in the whole province in 2020 were estimated based on population data released by Henan Provincial Bureau of Statistics.Age-standardized rates were calculated according to the age-standardized rate of Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW).Joinpoint 5.4.0 soft-ware was used to construct a regression model to analyze the changing trends of malignant tumors from 2010 to 2020,and the average annual percentage change(AAPC)and 95％confidence in-terval were calculated.[Results]In 2020,the estimated number of new cancer cases in Henan Province was 299 148,with a crude incidence rate of 259.38/105,ASIRC of 201.09/105(204.56/105 for males and 200.45/105 for females)and ASIRW of 196.46/105(203.43/105 for males and 192.22/105 for females).The ASIRC was higher in urban areas(208.10/105)than that in rural areas(197.74/105).The top five cancer types in male were lung,stomach,liver,esophagus,and colorectal cancers,while the top five in female were breast,lung,thyroid,cervical,and esophageal cancers.The estimated number of cancer deaths was 172 070,with a crude mortality rate of 149.20/105 and ASMRC of 106.52/105(137.22/105 for males and 78.04/105 for females)and ASMRW of 106.24/105(137.05/105 for males and 77.91/105 for females).The ASMRC was higher in rural areas(109.92/105)than that in urban areas(99.49/105).The top five causes of cancer death in male were lung,stomach,liver,esophagus,and colorectal cancers,and those in female were lung,esophagus,stomach,liver,and breast cancers.From 2010 to 2020,the trends of ASIRC remained stable(AAPC=0.14％,P=0.572),while the ASMRC showed a significant decreasing trend(AAPC=-1.46％,P=0.011).[Conclusion]Lung cancer,breast cancer and digestive system cancers are the main malignant tumors threatening the health of residents in Henan Province.The incidence and mor-tality of common malignant tumors show significant gender and urban-rural differences.It is neces-sary to further optimize the prevention and control of malignant tumors,formulate targeted inter-vention strategies based on population characteristics,and improve the health awareness of the whole population.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Glycosylation modification is an important post-translational modification of proteins, which participates in regulating protein half-life, biological activity, and immunogenicity, thereby affecting their functions. Glycoproteins expressed in Pichia pastoris predominantly carry high-mannose type glycans, primarily composed of mannose residues, which starkly contrasts with the complex-type glycans synthesized by mammalian cells. This study aims to transform the high mannose glycosylation modification of P. pastoris into a hybrid glycosylation modification similar to that of mammalian cells through genetic engineering technology. We introduced the mannosidase Ⅰ gene (MDSⅠ) from Trichoderma viride and the human β-1,2-N-acetylglucosaminyltransferase I gene (GnTⅠ) into a previously constructed P. pastoris strain (∆och1) capable of producing Man₈GlcNAc₂ glycans. To precisely regulate the expression of MDSⅠ and GnTⅠ, we designed various promoter combinations, including the strong inducible AOX promoter and the constitutive GAP promoter. The receptor-binding domain (RBD, residues 377-588) of the spike protein from the Middle East respiratory syndrome coronavirus (MERS-CoV) was selected as the reporter protein for this investigation (MERS-RBD). The N-glycosylation profile of MERS-RBD was systematically analyzed using PNGase F digestion coupled with mass spectrometry. The results showed that after the knockout of och1 and the introduction of MDSⅠ and GnTⅠ genes with different promoter combinations, P. pastoris strains capable of producing GlcNAcMan₅GlcNAc₂ glycans were successfully generated. When the AOX promoter was used to control the MDSⅠ gene and the GAP promoter was used to control the GnTⅠ gene, the engineered strain exhibited the highest proportion of hybrid-type GlcNAcMan₅GlcNAc₂ glycans, which accounted for 68.38% of the total N-glycosylation. In conclusion, we successfully engineered a P. pastoris strain capable of synthesizing hybrid-type GlcNAcMan₅GlcNAc₂ glycans, establishing a foundation for subsequent research on the biosynthesis of complex-type N-glycans in P. pastoris.
Glycosylation ; Glycoproteins/genetics* ; Polysaccharides/metabolism* ; N-Acetylglucosaminyltransferases/metabolism* ; Pichia/metabolism* ; Humans ; Mannosidases/metabolism* ; Genetic Engineering ; Trichoderma/genetics* ; Recombinant Proteins/genetics* ; Saccharomycetales

ObjectiveThe significance of adverse childhood experiences (ACEs) among men who have sex with men (MSM) should not be overlooked. This study aims to assess the reliability and validity of the Chinese version of the Adverse Childhood Experiences-International Questionnaire (ACE-IQ) among the MSM population in China to evaluate its applicability in this group. MethodsA cross-sectional survey was conducted in three Chinese cities(Shanghai, Shenyang and Kunming) using snowball sampling, with a total of 1 130 MSM participants included. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the structural validity of the scale. Internal consistency reliability was evaluated using Cronbach’s α coefficient, and split-half reliability was assessed with the Spearman-Brown coefficient. ResultsAccording to the EFA results, after removing item ACE10 (“parental death”), the 23-item ACE-IQ demonstrated a six-factor structure, including victimization or witnessing emotional/physical abuse, sexual abuse, physical neglect, family dysfunction, emotional neglect, and peer violence. CFA results indicated a good model fit for the six-factor model, supporting the EFA findings. The scale demonstrated good reliability, with a Cronbach's α coefficient of 0.852 and a Spearman-Brown coefficient of 0.899, indicating high internal consistency and split-half reliability within the studied population. ConclusionThe Chinese version of the ACE-IQ demonstrates satisfactory reliability and validity among MSM population, supporting its suitability for assessing ACEs in this group. The findings provide an empirical basis for subsequent mental health interventions.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

[Purpose]To analyze the incidence and mortality rates of female breast cancer in Henan Province in 2020 and the trends from 2010 to 2020.[Methods]Breast cancer incidence and mor-tality data stratified by urban and rural areas and age groups were collected from Henan Provincial tumor registry,and the province's household population statistics were used.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),cumulative rate(0～74 year old)were calculated.The annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated using Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2020.[Results]In 2020,24 744 new cases and 4 989 deaths of female breast cancer were documented in Henan Province,with a crude incidence rate of 46.96/105,ASIRC of 38.43/105 and ASIRW of 35.71/105;a crude mortality rate of 9.47/105,ASMRC of 6.80/105 and ASMRW of 6.72/105,respectively.The above indicators in urban areas were signifi-cantly higher than those in rural areas.The highest incidence was observed in the age group of 50～54 years old,while the highest mortality reached in the age group of 85 years old and above.From 2010 to 2020,the overall incidence of female breast cancer showed a slow upward trend(AAPC=2.09％,95％CI:0.62％～3.58％,P=0.010),while the mortality rate exhibited a signif-icant downward trend(AAPC=-3.49％,95％CI:-5.62％～-1.30％,P=0.005).[Conclusion]The incidence and mortality rates of female breast cancer in Henan Province are still at a high level,and corresponding preventive measures and control strategies are needed to effectively reduce the health hazards of breast cancer to women.