Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To analyze the prevalence and risk factors of underscreening among cervical cancer screening participants in Wuxiang County,Shanxi Province in 2019,providing evidence-based support for optimizing mobilization strategies.Methods Data from cervical cancer screening programs conducted between 2019 and 2024 in Wuxiang County were retrospectively collected.The follow-up screening behaviors of women screened in 2019 were analyzed,and factors associated with underscreening were identified.Results A total of 3759 women underwent cervical cancer screening in 2019.Among them,492 women(13.09％)with abnormal primary screening results requiring follow-up in 12 months,yet only 43(8.74％)completed;2154 women(57.30％)with negative liquid-based cytology testing(LCT)results needed re-screening after 3 years,701(32.54％)completed;1113 women(29.61％)with negative HPV/combined results needed re-screening after 5 years,734(65.95％)completed.Overall,2299 women(60.69％)exhibited underscreening.Multivariate analysis showed that underscreening was more likely among community residents than rural residents(OR=2.309,P=0.018),older women(OR=1.065,P＜0.001),those in organized screening compared to opportunistic screening(OR=3.789,P＜0.001),those undergoing LCT(OR=4.607,P＜0.001)or combined screening instead of human papillomavirus testing(OR=3.624,P＜0.001),and those with abnormal screening results(OR=6.859,P＜0.001).Conclusion Substantial proportions of cervical cancer screening participants demonstrate poor adherence to guideline-recommended screening intervals,and particularly need to focus on older women and those with abnormal screening results.Implementation of electronic screening record systems and emphasizing knowledge of periodical screening in health education could enhance compliance with"70％screening coverage"target for cervical cancer prevention.

Objective To analyze the prevalence and risk factors of underscreening among cervical cancer screening participants in Wuxiang County,Shanxi Province in 2019,providing evidence-based support for optimizing mobilization strategies.Methods Data from cervical cancer screening programs conducted between 2019 and 2024 in Wuxiang County were retrospectively collected.The follow-up screening behaviors of women screened in 2019 were analyzed,and factors associated with underscreening were identified.Results A total of 3759 women underwent cervical cancer screening in 2019.Among them,492 women(13.09％)with abnormal primary screening results requiring follow-up in 12 months,yet only 43(8.74％)completed;2154 women(57.30％)with negative liquid-based cytology testing(LCT)results needed re-screening after 3 years,701(32.54％)completed;1113 women(29.61％)with negative HPV/combined results needed re-screening after 5 years,734(65.95％)completed.Overall,2299 women(60.69％)exhibited underscreening.Multivariate analysis showed that underscreening was more likely among community residents than rural residents(OR=2.309,P=0.018),older women(OR=1.065,P＜0.001),those in organized screening compared to opportunistic screening(OR=3.789,P＜0.001),those undergoing LCT(OR=4.607,P＜0.001)or combined screening instead of human papillomavirus testing(OR=3.624,P＜0.001),and those with abnormal screening results(OR=6.859,P＜0.001).Conclusion Substantial proportions of cervical cancer screening participants demonstrate poor adherence to guideline-recommended screening intervals,and particularly need to focus on older women and those with abnormal screening results.Implementation of electronic screening record systems and emphasizing knowledge of periodical screening in health education could enhance compliance with"70％screening coverage"target for cervical cancer prevention.

OBJECTIVE: To evaluate the effect of different cumulative energy composite parameters on the outcomes of phacoemulsification cataract surgery in patients with type 2 diabetes mellitus. METHODS: A total of 252 patients with cataract (involving 252 eyes) and type 2 diabetes mellitus received phacoemulsification cataract surgery in our hospital between January, 2017 and June, 2019. The patients were divided into group A (150 cases) and group B (102 cases) for cataract phacoemulsification with cumulative energy composite parameters of 8 and 10, respectively, and 90 nondiabetic patients received cataract phacoemulsification with a cumulative energy composite parameters of 10 served as the control. The macular thickness, best corrected visual acuity, visual acuity, and postoperative leakage in the 3 groups were evaluated at 1 week, 1 month, and 3 months after the surgery. RESULTS: The visual acuity was significantly improved after phacoemulsification better in all the 3 groups. At 3 months after the surgery, the proportions of patients with visual acuity ratio < 0.1 or >1.0, macular thickness, best corrected visual acuity and permeability differed significantly between groups A and B ( < 0.05), but not between group A and the control group ( > 0.05). At 1 month and 3 months after the surgery, the proportion of patients with visual acuity ratio < 0.1 was significantly lower and the rate of visual acuity ratio >1.0 was higher in group A than in group B. At 1 month after the operation, the total leakage rate in group A (31.1%) was higher than that in the control group (21.1%) but comparable with that in group B; at 3 months, the total leakage rates were significantly lower in group A than in group B (10.0% 32.4%, < 0.05), and the leakage resulted mainly from local and diffuse permeation. CONCLUSIONS Phacoemulsification can effectively improve the visual acuity of cataract patients especially in non-diabetic patients. A lower cumulative energy composite parameter achieves better outcomes in type 2 diabetic patients with cataract. The macular thickness, local infiltration and diffuse leakage can be used as indicators for assessing visual recovery and stabilization after phacoemulsification.
Cataract ; Cataract Extraction ; Diabetes Mellitus, Type 2 ; Humans ; Phacoemulsification ; Visual Acuity

Objective To explore the effects of two routes of melatonin (MT) administration including intraperitoneal and caudal vein injection on the behavior,histopathology and the expression of myelin basic protein (MBP) and active caspase-3 protein in focal cerebral ischemic rats.Methods 84 male Sprangue-Dawley rats were randomly divided into normal control group (CON,n=12),middle cerebral artery occlusion group(MCAO,n=24),MT-intraperitoneal group (n=24) and MT-intravenous injection group (n=24) by random number table.Twenty-four hours after ischemia reperfusion (IR),Morris water maze was used to observe the effects of two routes of MT administration on behavior in focal cerebral ischemic rats.7 d after IR,MBP immunohistochemical and hematoxylin eosin (HE) staining were used to examine the expression of MBP in striatum and histopathological changes in hippocampal CA1 region.24 h,72 h and 7 d after IR,the expression of active caspase-3 in hippocampal CA1 region was observed by immunohistochemical staining.Results The average escape latencies in Morris water maze in MT-intravenous injection group at different time points were all lower than those of the MT-intraperitoneal,and they were all lower than those of the MCAO group.Swimming time percentage of target quadrant in MT-intravenous injection group were higher than those of the MT-intraperitoneal,and they were all higher than those of the MCAO group (all P＜0.01);7 d after IR,the results of HE staining showed that the hippocampus cells in MCAO group were disarranged with hyperchromatic nucleus and cytoplasm.More hippocampal cells were observed in MT-intraperitoheal and MT-intravenous injection groups,and they were relatively well arranged.The optical density (OD)of MBP in MT-intravenous injection group (105.60±4.04) was significantly higher than those in MCAO group (95.60±2.07) and MT-intraperitoneal injection group (98.00±4.18) (both P＜0.01).Immunohistochemical results showed that the number of active caspase-3 positive cells in MT-intravenous injection group ((116.93± 12.58)/mm2,(130.16±21.22)/mm2,(88.25±7.80)/mm2) at each time point were significantly lower than those in MT-intraperitoneal injection group ((156.64± 32.54)/mm2,(176.49± 17.44)/mm2,(127.96±16.73)/mm2) (all P＜0.05).At the time points of 24 h and 72 h after IR,there were less active caspase-3 positive cells in MT-intraperitoneal and MT-intravenous injection group compared with those in MCAO group((273.56±32.54)/mm2,(288.63±35.17)/mm2)(all P＜0.01).Conclusion MT administration by both intraperitoneal and intravenous injection can significantly improve the behavior and attenuate the histopathology and white matter damage,and reduce the cell apoptosis in hippocampal CA1 region in focal cerebral ischemic rats,and the therapeutic effects of MT-intravenous injection are better than MT-intraperitoneal injection.

Objective To investigate the effects of music therapy in treating cognitive dysfunction in early stroke patients. Methods Forty patients who had suffered a stroke in the previous four weeks were randomly di-vided into two groups of 20. One received music therapy as part of their cognitive training ( observation group) , and the other did not (control group). Before and after 6 weeks of treatment, cognitive functioning was evaluated using the second Chinese edition of Loewenstein's occupational therapy cognitive assessment (LOTCA). The patients' a-bility in the activities of daily living was also evaluated using the modified Barthel index (MBI). Results After treatment, the total LOTCA and MBI scores in both groups were significantly higher than before. Both LOTCA and MBI scores in the observation group were significantly higher than in the control group, and there were also signifi-cant differences between the observation and control groups on all of the LOTCA sub-items except spatial percep-tion. Conclusions Music therapy can improve the effects of rehabilitation on cognition and the ADL ability of early stroke patients.

Objective To understand the genetic characterization of HA1 gene of influenza A H3N2 viruses circulated in recent years in Hebei.Methods Viral RNAs of 25 H3N2 strains were extracted and amplified by Reverse Transcription Polymerase Chain Reaction (RT-PCR).The products of PCR were purified and sequenced,and the sequences were analyzed though biometic software.Results Several amino acid substitutions located in antigenic sites or receptor binding sites were found more in the isolates than the current vaccine virus or the isolates from previous year.Amino acid substitution was found in 3,140,142,144,145,158,159,189,192,193,198,204,225,226 and 227 positions in the isolates during 2003-2008,more amino acid substitutions took place in antigenic determinant A,B and receptor binding site (RBS).New phylogenetic branches appeared continuously during 2003-2008.The H3N2 strains of the same year almost clustered in the same group on the phylogenetic tree.Conclusions Amino acid substitutions continuously occurred in the HA1 genes in influenza A H3N2 viruses isolated in Hebei from 2003 to 2008,it is meaningful to pay close attention to the HA1 variation in order to prevent and control influenza.

The gene smu. 776 encodes a possible S-adenosylmethionine-dependent methyltransferase of 385 residues in Streptococcus mutans, a primary pathogen for human dental caries. The DNA fragment of smu.776 was cloned into pET28a and expressed in good amount from the E. coli strain BL21 (DE3). Smu.776 protein was purified to homogeneity in a two-step procedure ofNi2+ chelating and size exclusion chromatography. Crystals were obtained by hanging-drop vapor diffusion method and diffracted to 2.0 (A) resolution.The crystal belongs to orthorhombic space group C2 with cell dimension of a=168.47 (A), b= 50.66 (A), c=53.96 (A), β=104.22°. The asymmetric unit is expected to contain one molecule with solvent content of 51.3%.

Smu. 260 encodes a putative protein of 200 residues in Streptococcus mutans, a primary pathogen for human dental caries. Smu. 260 was cloned into expression vector pET28a and expressed in good amount trom the E. coli strain BL21 (DE3). Smu.260 protein was purified to homogeneity in a two-step procedure of Ni2+ chelating and size exclusion chromatography. The purified protein exists in two forms, a dimer form about 46 ku with yellow color and a tetramer form without apparent color. Crystals were obtained from the dimer protein by hanging-drop vapor-diffusion method. The crystals diffracted to about 2.3 A resolution and belong to orthorhombic space group P212121 with cell dimensions of a = 89.88A, b = 90.91 A, c = 105.17 A. The asymmetric unit is expected to contain two dimers with solvent content of 53%.