As a mature neuromodulation technique with sufficient evidence and wide application， transcranial magnetic stimulation （TMS） has become a highly promising approach for the treatment of insomnia disorder. However， there is still a lack of unified standards for formulation of treatment regimens， technical operations， indications and contraindications， treatment of adverse reactions， and application in special populations. In order to standardize the application of TMS in the diagnosis and treatment of insomnia disorder， Professional Committee of Sleep and Neuromodulation of Chinese Sleep Research Society organized the compilation of the technical specifications. This document systematically elaborates on the technical principles and stimulation modes of TMS， summarizes the clinical evidence for its application in the treatment of primary insomnia disorder and comorbid conditions such as depression and cognitive impairment， clarifies the key points for formulating treatment regimens （including stimulation coils， targets， modes， and intensity）， refines the technical specifications such as treatment room setup， personnel qualifications， operation procedures， and efficacy evaluation， and provides recommendations for the management of adverse reactions and principles for use in special populations， which provides a comprehensive expert consensus and practical guidance for the standardized clinical application of TMS in the treatment of insomnia disorder.

AIM: To investigate expression differences and mechanism of action of serine/threonine kinase 1(AKT1), ATP synthase F1 subunit(ATP5F1), and Bcl-2-associated anti-apoptotic gene 3(BAG3)in the occurrence and progression of pterygium.METHODS:Pterygium-related gene expression data were retrieved from GEO database to screen differentially expressed genes(DEGs). String and Cytoscape were used to construct protein-protein interaction(PPI)networks and identify core targets. GO/KEGG enrichment analyzed mitochondrial metabolic pathways. The pterygium samples(head/body)were collected; pathological features were evaluated by HE staining, and the expression of AKT1, ATP5F1, and BAG3 was detected via immunohistochemistry(IHC).RESULTS:A total of 1 264 DEGs were identified(585 upregulated, 679 downregulated). GO analysis showed significant enrichment of mitochondrial pathways regarding to biological processes, cell components and molecular functions; KEGG analysis highlighted oxidative phosphorylation and chemical carcinogenesis-reactive oxygen species(ROS)pathways. The head and body pterygium samples were collected from 28 cases(28 eyes)that received pterygium surgery, including 7 males(7 eyes)and 21 females(21 eyes), with a mean age of 69.32±8.98 years. HE staining showed more severe dysplasia, disordered stroma, and inflammation in the pterygium head versus the body. IHC detection confirmed significantly lower AKT1, ATP5F1, and BAG3 expression in the head compared with the body(all P<0.05).CONCLUSION:GEO-based bioinformatics and experiments confirmed that AKT1/ATP5F1/BAG3(mitochondrial genes)had significant differential expression in pterygium, correlating with pathological progression. They may regulate mitochondrial metabolism to mediate pterygium progression, offering new insights for targeted therapy.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

Objective To investigate the clinicopathological characteristics, diagnostic key points, and treatment strategies of penile metastatic extramedullary plasmacytoma(EMP). Case Report A 47-year-old male patient presented with a painless indurated nodule on the dorsal side of the penis and had a previous history of plasmacytoma in the nasal cavity and tibia. He subsequently underwent complete excision of the penile lesion. Postoperative histopathological examination confirmed the diagnosis of anaplastic plasmacytoma. Immunohistochemical analysis showed positive staining of CD138, CD38, MUM1, and CD79a, with Ki-67(+60%). Light chain restriction was also identified. No local recurrence or distant metastasis was observed during the 5-month follow-up. Conclusion Metastatic EMP of the penis is an extremely rare condition, and the diagnosis relies on pathological examinations combined with immunohistochemical analysis. Surgical resection can be an effective treatment modality for localized lesions;however, long-term follow-up is essential to monitor disease progression.

ObjectiveTo focused on patients with unexplained repeated implantation failure （URIF） and compare the clinical efficacy of different administration routes of granulocyte colony-stimulating factor （G-CSF） in patients undergoing frozen-thawed embryo transfer cycles. MethodsA retrospective case-control study was conducted. A total of 187 patients with URIF who received medical treatment were enrolled in this study. According to whether G-CSF was used on the day of endometrial transformation and its administration route in frozen-thawed embryo transfer cycles， the patients were divided into three groups： control group （without G-CSF， n=71）， subcutaneous injection group （subcutaneous G-CSF， n=72）， and intrauterine infusion group （intrauterine G-CSF infusion， n=44）. The pregnancy outcomes among the three groups were compared， and Logistic regression analysis was performed. ResultsThere were significant differences in biochemical pregnancy rates among the three groups （P<0.05）， indicating statistical significance in the overall comparison. In terms of numerical trend， the biochemical pregnancy rate was in the order： subcutaneous injection group > intrauterine infusion group > control group. Further pairwise comparison showed that only the difference between the subcutaneous injection group and the control group was statistically significant （P<0.017）， while no significant differences were found between the other groups （P>0.017）. The overall comparison of early miscarriage rates among the three groups also showed a significant difference （P<0.05）， indicating a statistically significant difference in the distribution among the groups. The numerical trend was： intrauterine perfusion group > subcutaneous injection group > control group. Pairwise comparison results showed that only the difference between the intrauterine perfusion group and the control group was statistically significant （P<0.017）， while there was no statistically significant difference between any other two groups （P>0.017）.Multivariate Logistic regression analysis showed that endometrial thickness on the day of transformation， number of transferred embryos， and subcutaneous G-CSF injection were independent factors associated with an increased biochemical pregnancy rate， where as age was an independent factor for a decreased biochemical pregnancy rate. For clinical pregnancy outcome， endometrial thickness on the day of transformation， number of transferred embryos， and subcutaneous G-CSF injection were also independent factors for an increased clinical pregnancy rate， while BMI was an independent factor for a decreased clinical pregnancy rate. ConclusionSubcutaneous injection of G-CSF only improved the biochemical pregnancy rate in URIF patients. Multivariate Logistic regression analysis showed that subcutaneous G-CSF injection was a favorable factor for clinical pregnancy rate in URIF patients； however， no significant improvement in clinical pregnancy rate was observed among the three groups. Both the comparison of pregnancy outcomes and the results of multivariate logistic regression analysis indicates that intrauterine perfusion of G-CSF has no significant therapeutic effect in the treatment of patients with URIF.

OBJECTIVES: To investigate the role of PTEN-induced putative kinase 1 (PINK1) in regulating the viability, migration, and apoptosis of colorectal cancer (CRC) cells, and to explore its potential epigenetic mechanisms. METHODS: PINK1 was overex-pressed or knocked down in HCT116 and DLD1 CRC cell lines using lentiviral vectors, with efficiency verified by qRT-PCR and Western blotting. Cell proliferation, colony formation, migration, and apoptosis were assessed using CCK-8, colony formation, wound healing, Transwell, and Hoechst 33258 staining assays, respectively. Protein levels of apoptosis-related and histone modification-related markers were analyzed by Western blotting. Genome-wide chromatin accessibility was profiled using ATAC-seq. RESULTS: PINK1 expression was significantly downregulated at both mRNA and protein levels in CRC tissues compared to normal tissues. PINK1 overexpression inhibited cell prolifera-tion, colony formation, and migration in HCT116 and DLD1 cells (all P<0.05), whereas PINK1 knockdown promoted these malignant phenotypes (all P<0.05). PINK1 overex-pression induced apoptosis, associated with decreased levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) and increased pro-apoptotic Bax (all P<0.05), without altering p53 expression. Mechanistically, PINK1 overexpression reduced the expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 27 trimethylation (H3K27me3), and increased the expression of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 27 acetylation (H3K27ac). It also downregulated key histone-modifying enzymes, including EZH2, EZH1, SUZ12, and histone deacetylase 3 (HDAC3) (all P<0.01). ATAC-seq revealed that PINK1 overexpression increased chromatin accessibility, particularly around transcription start sites. CONCLUSIONS PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

Objective:To establish a rapid and effective melanin-bleaching method to standardize and improve the molecular pathological analyses of melanoma.Methods:Fifteen cases of melanoma with melanin content exceeding 50% collected at the Precision Pathology Diagnosis Center, Weifang People′s Hospital, Weifang, China between 2023 and 2024 were included in the study. These tissue samples were subject to melanin-bleaching treatments using H 2O 2, potassium permanganate (KMnO 4), Tris-HCl or PBS method. The bleaching effects in each group were evaluated using hematoxylin and eosin (HE) staining. Thereafter, the total amount, purity, and integrity of DNA extracted from bleached tissues were analyzed using UV spectrophotometry and Qsep1 Bio-fragment analyzer. Finally, in order to compare the efficiency of DNA amplification, C-KIT and PDGFRA were examined using Sanger sequencing, and BRAF was detected using real-time quantitative PCR. Results:Among the 15 cases, there were seven males and eight females whose median age was 68 (range, 63 to 71) years. Bleached tissue in Tris-HCl group had the highest HE score, which was significantly higher than those in the groups of PBS, H 2O 2, KMnO 4, and control ( F=113.3, P<0.05). The total DNA amount in the control and Tris-HCl groups was significantly higher than those in the groups of PBS, H 2O 2, and KMnO 4, respectively ( F=275, P<0.05). Meanwhile, the mean A260/ A280 values of DNA obtained from bleached tissue in Tris-HCl and KMnO 4 were better than that of control, and the mean A260/ A230 values of Tris-HCl and KMnO 4 were higher than that of control, PBS, and H 2O 2. Meanwhile, the proportion of >5 000 bp,>3 000 bp, and >1 000 bp DNA fragments in Tris-HCl was all significantly higher than those in other groups ( F=147.9, F=127.9 and F=61.9, respectively, P<0.05). C-KIT and PDGFRA genes were both successfully amplified based on DNA obtained from bleached tissue in Tris-HCl group, and the sequencing peaks were clear and free of noticeable noises. Real-time quantitative PCR results showed that Tris-HCl method had lower cycle threshold values than other methods in detecting BRAF gene ( F=30.36, P<0.05). Conclusions:Tris-HCl method is a fast and effective melanin-bleaching method for analyzing melanoma, which could remove melanin effectively, confirm high quality of DNA and good integrity of DNA, and improve the amplification efficiency of sequencing for melanoma related genes. This new method may help pathologists with reliable molecular typing and identifying therapeutic targets for melanoma. It may greatly improve clinical management of melanoma patients.

Objective Idiopathic rolandic epilepsy syndrome （IRES） is the most common epilepsy syndrome in childhood， and its lesion site remains undetermined. This article aims to investigate the source of epileptiform discharges in IRES using magnetoencephalography （MEG）.Methods A total of 70 patients with IRES were enrolled in this prospective MEG-based study， among whom there were 53 children with benign epilepsy of childhood with centrotemporal spikes （BECTS）， 12 children with atypical benign partial epilepsy （ABPE）， 3 children with Landau-Kleffner syndrome （LKS）， and 2 children with epileptic encephalopathy with continuous spike-and-waves during slow-wave sleep （CSWS）. Epileptiform discharges were collected independently from each patient 10 times， and an MEG source analysis was performed. Standardized low-resolution brain electromagnetic tomography was used to perform source localization of the distributed source model. The spike source density was quantified into amplitude， and source location was determined according to the Desikan-Killiany atlas. The association between the distribution of spike source in brain and clinical manifestations was analyzed.Results In IRES， there were significant differences in the source locations of epilepsy discharge between BECTS， ABPE， LKS， and CSWS. The current source density of CSWS was stronger in the frontal lobe， the temporal lobe， and the anterior cingulate gyrus， while that of ABPE was stronger in the frontal lobe， and that of BECTS and LKS were stronger in the temporal lobe. The more severe phenotype of epilepsy， such as generalized tonic-clonic seizure， was associated with a stronger current source density in the brain， which was consistent with electroencephalography manifestations.Conclusion This study identifies different sources of epileptiform discharges in IRES. The density distribution of these spike sources may help to explain the discharge， cognitive， and neuropsychological characteristics in different subtypes of IRES.
Magnetoencephalography