Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective To observe the effect of comorbidity for patients with non-small cell lung cancer (NSCLC) on exercise tolerance and cardiopulmonary function. Methods NSCLC patients who underwent cardiopulmonary exercise testing (CPET) before surgery were retrospectively included. According to the Charlson comorbidity index (CCI) score, patients were divided into two groups: a CCI≥3 group and a CCI＜3 group. The patients were matched with a ratio of 1 : 1 by propensity score matching according to the age, body mass index, sex, smoking history, exercise habits, pathological stage and type of surgery. After matching, CPET indexes were compared between the two groups to explore the differences in exercise tolerance and cardiopulmonary function. Results A total of 276 patients were included before matching. After matching, 56 patients were enrolled with 28 patients in each group, including 38 (67.9%) males and 18 (32.1%) females with an average age of (70.7±6.8) years. Compared with the CCI＜3 group, work rate at peak (WR peak), WR peak/predicted value (WR peak%), kilogram oxygen uptake at anaerobic threshold (VO2/kg AT), VO2/kg peak, VO2/kg peak%, peak carbon dioxide output, the minute ventilation to carbon dioxide production slope, O2 pulse peak and O2 pulse peak% of CCI≥3 group were statistically different (P＜0.05). Among them, the rate of postoperative pulmonary complication in the CCI≥3 group was higher than that in the CCI＜3 group (60.7% vs. 32.1%, P=0.032). Conclusion In the NSCLC patients, exercise tolerance and cardiopulmonary function decreased in patients with CCI≥3 compared with those with CCI<3. CPET can provide an objective basis for risk assessment in patients with comorbidity scored by CCI for pulmonary resection.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective To observe the effect of intelligent flexible ankle stretching training on lower extremity spasm in patients with spinal cord injury. Methods From June,2021 to May,2024,28 patients with spinal cord injury were randomly divided into control group(n=14)and experimental group(n=14).Both groups received conventional rehabilitation treatment.On this ba-sis,the control group received manual extension treatment,and the experimental group received intelligent flexi-ble ankle stretching system training,for eight weeks.The modified Ashworth Scale(MAS),ankle dorsiflexion an-gle,Clinical Spasticity Index(CSI),max root mean square(RMSmax)of surface electromyography of gastrocne-mius medial head and vibration perception threshold(VPT)of great toe were compared. Results After treatment,MAS(χ2=10.378,P=0.035),ankle dorsiflexion angle(Z=-3.306,P<0.001),CSI(t=4.101,P=0.001)and RMSmax of gastrocnemius medial head(Z=-3.296,P<0.001)improved in the experimental group,while MAS(χ2=11.418,P=0.022),ankle dorsiflexion angle(Z=-1.986,P=0.047)and RMSmax of gas-trocnemius medial head(Z=-2.297,P=0.021)were better in the experimental group than in the control group.Although VPT was improved after treatment,no significant difference was found within and beteen groups(P>0.05). Conclusion The intelligent flexible ankle stretching training could improve the lower limb muscle spasticity in patients with spinal cord injury,and may be benefit for foot proprioception.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective: To understand the trend of changes of hygiene status in the teaching environment among primary and secondary schools in Beijing City during 2016-2020, so as to provide basis for further improving the teaching environment and campus hygiene conditions in primary and secondary schools. Methods: A proportional systematic sampling method covered over 50% of schools selected annually in Beijing from 2016 to 2019, and 34% were selected in 2020. Two representative classrooms were selected from each selected school for testing based on their structure and other factors, with 6 196 classrooms supervised, from 2016 to 2020,1 330,1 312,1 384,1 322,848 classrooms were monitored for each year. Results: From 2016 to 2020, the overall lighting qualification rate of classrooms (lighting coefficient 72.8%, window to floor area ratio 41.8%, rear wall reflectance ratio 42.2%, blackboard reflection ratio 37.4%), the overall qualification rate of average blackboard illumination and uniformity (50.6%, 34.9 %), and the overall qualification rate of desk and chair allocation (58.6%) were all below 80%. The overall qualification rate of per capita classroom area (87.5%), blackboard size (83.2%), average desk illumination ( 80.1% ), average desk illumination and uniformity (82.9%), the distance between lamp and desk (99.1%), carbon dioxide ( 86.6% ), temperature (84.9%), and noise (96.6%) were all above 80%. The following indicators, blackboard size, the distance between lamp and desk, average blackboard illumination, lighting coefficient, blackboard reflectance, rear wall reflectance, carbon dioxide, temperature, and noise ( χ 2=78.38, 9.71, 11.76, 320.59, 37.63, 58.45, 236.45, 1 347.56, 101.97), had statistically significance between years. Among those indicators, the qualified rates of blackboard size, blackboard reflectance, lighting coefficient, and noise had been increasing year by year ( χ 2 trend =69.98, 15.82, 240.02, 5.77) ( P <0.05). The qualified rates of per capita classroom area, window to floor area ratio, and blackboard reflection ratio in primary schools (81.6%, 39.8%, 36.3%) were all lower than those in secondary schools (94.9%, 44.5%, 40.3%) ( χ 2=246.32, 12.03, 10.51, P <0.05). The qualified rates of blackboard size, average blackboard illumination, average blackboard illumination and uniformity, and desk and chair allocation (89.3%, 55.6% , 36.0%, and 60.2%) were all higher than those in secondary schools (75.4%, 44.1%, 33.3%, and 56.5%) ( χ 2=209.33, 78.41, 4.44, 8.22) ( P <0.05). The qualified rates of average desk illumination and uniformity, average blackboard illumination, rear wall reflectance ratio, desk and chair allocation, carbon dioxide, temperature, and noise indicators in urban area (82.9%, 84.1% , 51.9%, 45.0%, 60.9%, 91.2%, 89.5%, 97.8%) were all higher than those in suburban area (77.3%, 81.7%, 49.2%, 39.5%, 56.3%, 82.3%, 80.4%, 95.5%) ( χ 2=31.16, 6.28, 4.36, 16.40, 13.39, 105.29, 98.23, 24.66， P <0.05). The qualified rates of the distance between lamp and desk, lighting coefficient, window to floor area ratio, blackboard size, blackboard reflection ratio, average blackboard illumination and uniformity, and per capita classroom area in urban areas (98.8%, 65.2%, 34.3%, 76.7%, 35.9%, 30.1%, 84.6%) were all lower than those in suburban areas (99.4%, 81.4%, 49.8%, 89.7%, 40.2%, 39.6%, 90.3%) ( χ 2=6.80, 171.67, 132.43, 188.46 , 12.45, 60.28, 44.82) ( P <0.05). Conclusions The main problems in the teaching environment of schools in Beijing are classroom lighting, as well as desk and chair allocation. The findings suggest technical rationality and operability of relevant standard should be considered when under revision, and standard training and supervision management should be strengthened, with the aim of teaching environment improvement.

OBJECTIVE: To analyze the safety and effectiveness of 3D printing prefabricated nail path model assisted lumbosacral hemivertebra orthopaedic surgery. METHODS: A retrospective analysis was performed on 8 patients with lumbosacral hemivertebra deformity admitted from January 2016 to July 2021, including 3 males and 5 females, aged 6 to 15 at the time of surgery. The hemivertebra of 4 cases located on the left side and 4 cases on the right side. The hemivertebra of 1 case located at L_2,3, 2 cases at L_3,4, 2 cases at L_4,5, and 3 cases at L₅S₁. Four cases were fully segmented hemivertebra and 4 cases were incomplete segmented hemivertebra. The patient CT data was imported into Mimics 21.0 software for modeling, and then the model data was imported into 3-Matic software. The vertebra requiring screw placement was selected to simulate the optimal screw placement angle and length, and the model was printed for preoperative planning and intraoperative guidance. All patients underwent orthopedic surgery with the aid of 3D printing preset nail path model. The safety and effectiveness of the 3D printing prefabricated nail tunnel model assisted lumbosacral hemivertebra orthopaedic surgery was evaluated by comparing the imaging parameters of the patients. The main outcome measures were the Cobb angle of the main curve, the Cobb angle of the proximal compensatory curve, the coronal balance index C₇ plumb line-center sacral vertical line(C₇PL-CSVL), the accuracy of nail placement, and the correction rate of scoliosis before surgery, 1 week and 1 year after surgery. RESULTS: All of 8 patients were followed up for 13 to 31 months. A total of 98 pedicle screws were placed in 8 patients. The number of pedicle screw grades A, B, C, D, E was 38, 46, 10, 4, 0 screws. The screws of grade A and B were defined as good position, the accuracy rate of screw placement was 85.7%. The Cobb angle of the main curve were 21° to 38° before operation, 5° to 11° at 1 week after operation, 7°to 12° at 1 year after operation. The Cobb angle of the proximal compensatory curve were 16° to 39° befoer operation, 7° to 12 °at 1 week after operation, 7° to 14° at 1 year after operation, the correction effect remained good with no correction loss. The coronal balance index C7PL-CSVL were 20 to 35 mm before operation, 11 to 18 mm at 1 week after operation, 10 to 16 mm at 1 year after operation, the coronal imbalance improved. The scoliosis correction rate was 65.6% to 84.2% 1 week after surgery, and 61.9% to 81.6% 1 year after surgery. CONCLUSION The use of 3D printing prefixed nail tunnel model in lumbosacral hemivertebra osteotomy is safe and effective, and can significantly improve patients' local deformities. It is a reliable method to assist lumbar sacral hemivertebra osteotomy.
Humans ; Printing, Three-Dimensional ; Female ; Male ; Adolescent ; Retrospective Studies ; Child ; Lumbar Vertebrae/surgery* ; Sacrum/abnormalities* ; Bone Nails ; Orthopedic Procedures/instrumentation*

Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342-centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference (P=0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients (P<0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues (t=1.56, P=0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 (t-values of -12.17, -23.26 and -388.57, respectively; all P<0.001). Knockdown of LINC00342 by transfecting si-LINC00342-1 and si-LINC00342-2 inhibited HNSCC cell proliferation (t-values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation (t-values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration (t-values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities (t-values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 (t-values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P-values<0.05). The LINC00342-centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342-regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.
Humans ; Female ; Male ; Squamous Cell Carcinoma of Head and Neck/genetics* ; RNA, Long Noncoding/genetics* ; Clinical Relevance ; Epithelial Cells ; Head and Neck Neoplasms/genetics*

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×10⁵, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.
Female ; Humans ; Adult ; Middle Aged ; Adenomyosis/pathology* ; Dysmenorrhea/therapy* ; Menorrhagia/pathology* ; Endometriosis/therapy* ; Retrospective Studies ; Infertility/complications* ; Magnetic Resonance Imaging