Objective: To evaluate the clinical efficacy and safety of micro-percutaneous nephrolithotomy (microPCNL) using Needle-perc in the oblique supine-lithotomy position for treating 1—2 cm lower-pole stones (LPSs)，by comparing it with flexible ureteroscopic lithotripsy (FURL)，so as to identify an effective surgical method for LPSs. Methods: We retrospectively analyzed the clinical data of 56 patients with isolated LPSs of 1—2 cm treated in our hospital during Jan.and Dec.2023.Patients were divided into two groups based on the treatment method：FURL (n=31) and microPCNL (n=25).General information and perioperative data were compared between the two groups. Results: All operations were successfully completed.The operation time was shorter in the microPCNL group than in the FURL group \[(46.5±10.1) min vs.(73.5±18.9) min，P<0.001\].Stone-free rate (SFR) was 92.0% in the microPCNL group and 71.0% in the FURL group (P=0.026).There were no significant differences in the average fall of hemoglobin level，serumc creatinine change level，hospitalization time and postoperative fever between the two groups. Conclusion: MicroPCNL in oblique supine-lithotomy position is a safe and effective treatment for 1-2 cm LPSs，with a higher SFR compared to FURL.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Radiotherapy is a first-line treatment for a variety of malignant tumors by inducing DNA damage to kill tumor cells. However, tumor cells have different sensitivities to radiotherapy, ultimately leading to different therapeutic effects. Histone acetylation, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), is involved in the regulation of cell radiation sensitivity by influencing DNA damage repair. The main mechanisms are recruiting DNA repair related proteins and mediating chromatin dynamic changes. In this article, the role of histone acetylation modification in tumor radiotherapy was reviewed, aming to provide the basis for the radiotherapy sensitization strategy based on histone acetylation.

[Objective]People infected with Hepatitis B are often divided into hepatitis B carriers and hepatitis B patients based on whether ALT is normal or not,and ALT ≥ 2UNL is one of the indications for clinical antiviral treatment,but no sufficient evidence to justify this. In order to explore the theoretical basis,the paper investigated the effects of hepatitis B virus(HBV) on hepatic stellate cells(HSCs).[Methods]A total of 132 chronic hepatitis B patients with different viral loads and ALT levels were randomly selected as the study subjects. Of these patients,those with ALT≥2UNL were treated with antiviral therapy and followed up for 24 weeks. The effects of HBV on HSCs before and after the treatment were compared and analyzed. HSCs proliferation was detected by MTT method,HSCs cell cycle by flow cytometry,and expression of TGF-β1,Smad3,Smad7,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins by RT-PCR and Western blotting,respectively.[Results]At the normal ALT level,HBV with different viral loads had no significant effect on the proliferation,cell cycle and cell secretion of the HSCs. At the abnormal ALT level,especially when ALT ≥ 2UNL,with the increase of virus loads,HSCs proliferation accelerated;cells in the G0/G1 phase decreased significantly and cells in the S and G2/M phases increased significantly;the expression of TGF-β1,Smad3,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins increased significantly,but Smad7 mRNA and protein expression decreased significantly,the differences were statistically significant. HBV showed a significantly lower effect on HSCs after the antiviral therapy than before.[Conclusions]This paper reveals the differential effects of HBV on HSCs at different ALT levels and presents a comparative analysis of the effects before and after the antiviral therapy,which provides a theroretical basis for identifying the ALT level as an indication for HBV antiviral therapy.

Objective:To investigate the efficacy and safety of nerve decompression surgery through the lateral-rectus approach for sacral plexus nerve injury after sacral fracture fixation.Methods:A retrospective study was conducted to analyze the 10 patients with combined sacral plexus nerve injury after sacral fracture fixation who had been admitted to Department of Orthopedics, Xiangya Hospital between May 2022 and May 2023. There were 2 males and 8 females with an age of 16.5 (15.0, 26.3) years. At the time of injury, the patients had been clearly diagnosed as sacral fracture combined with sacral plexus nerve injury. By the Denis classification of sacral fractures: 7 cases of type Ⅱ and 3 cases of type Ⅲ; sacral plexus nerve injury sites: 1 case of L 4, 8 cases of L 5, 7 cases of S 1, and 2 cases of S 2. All of them were treated with reduction and internal fixation via the posterior approach within 2 weeks after injury, but after surgery their manifestations of sacral plexus nerve injury still persisted which were confirmed by CT, magnetic resonance imaging and neuromuscular electromyography. Therefore, at (4.0±2.3) months after internal fixation, all patients were treated with nerve decompression surgery through the lateral-rectus approach. The operative time, intraoperative bleeding, length of hospitalization, Gibbons nerve damage score and neurological recovery at the last follow-up were recorded. Results:In the 10 patients, the operative time was (112.0±21.5) min, intraoperative bleeding (215.0±91.3) mL, and length of hospitalization 7.0 (6.0, 8.5) d. Intraoperatively, sacral plexus nerve compression was found in 9 cases (6 cases of nerve compression and pulling due to fracture displacement, 3 cases of nerve entrapment due to soft tissue scar adhesion), and 1 case of nerve root avulsion injury. No other intraoperative complications occurred. The 10 patients were followed up for (9.2±2.3) months after surgery. At the last follow-up, the Gibbons score for the 10 patients improved from preoperative 3.0 (3.0, 3.3) points to 1.0 (1.0, 2.0) point, and their British Medical Research Council (BMRC) nerve injury grading was improved from the preoperative grade 0.0 (0.0, 1.3) to grade 3.5 (2.8, 4.0) (1 case of M5, 4 cases of M4, 4 cases of M3, and 1 case of M2).Conclusion:The lateral-rectus approach is effective and safe for exploration and decompression of the sacral plexus nerve in patients combined with sacral plexus nerve injury despite sacral fracture fixation.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

Objective:To investigate the effects of improving the prenatal multidisciplinary consultation mode on the outcomes of fetuses with structural malformations.Methods:Clinical data of pregnant women attending the Prenatal Multidisciplinary Consultation Center, jointly established by the Obstetrics & Gynecology Hospital of Fudan University and the Children's Hospital of Fudan University from January 2004 to December 2019, were retrospectively collected and analyzed. In 2014, the center optimized the multidisciplinary consultation mode to achieve a more individualized approach to genetic testing based on more accurate imaging diagnosis and deeper cooperation between the obstetrics and pediatrics teams. Differences in the number of cases, structure of the diseases, genetic testing results, outcomes, and prognosis between the improved group (enrolled from January 2014 to December 2019) and the baseline group (enrolled from January 2004 to December 2013) were compared. The Chi-square test was used for statistical analysis. Results:(1) This study recruited 5 977 pregnant women, including 3 424 in the baseline group and 2 553 in the improved group. The main indications for consultation were fetal factors [97.2% (5 812/5 977)], among which congenital structural malformations accounted for 77.5% (4 503/5 812). There was a significant difference in the systematic distribution of congenital structural malformations between the two groups ( χ2=141.31, P<0.001). The proportion of malformations involving the central nervous, cardiovascular, and urinary systems ranked in the top three in both groups. (2) The percentage of women receiving genetic testing was higher in the improved group than in the baseline group [26.7% (682/2 553) vs. 15.9% (546/3 424), χ2=103.87, P<0.001] and the positive rate of genetic testing was also higher in the improved group [19.9% (136/682) vs. 9.9% (54/546). χ2=23.42, P<0.001]. (3) Among the 5 977 cases, 418 (7.0%) were lost to follow-up; 1 741 (29.1%) opted for pregnancy termination; 123 (2.2%) had intrauterine fetal death; and 3 695 (61.8%) were live births. The rate of pregnancy termination in the improved group was lower than that of the baseline group [27.7% (707/2 553) vs. 30.2% (1 034/3 424), χ2=4.45, P=0.035]. (4) In the 1 741 cases with pregnancy termination, fatal cardiovascular system malformations ( n=413, 23.7%), central nervous system malformations ( n=377, 21.7%), multiple malformations ( n=258, 14.8%), and chromosomal abnormalities ( n=162, 9.3%) were the main causes. The top five diseases leading to pregnancy termination were cleft lip and palate [59.0% (46/78)], meningocele (5/9), gastroschisis/omphalocele [49.3% (33/67)], diaphragmatic hernia [46.5% (33/71)], and skeletal malformations [40.9% (83/203)]. The rates of pregnancy termination due to gastroschisis/omphalocele, diaphragmatic hernia, and skeletal malformations in the improved group were all lower than those in the baseline group [57.4% (27/47) vs. 30.0% (6/20), χ2=4.23; 59.0% (23/39) vs. 31.3% (10/32), χ2=5.43; 51.8% (72/139) vs. 17.2% (11/64), χ2=21.72; all P<0.05]. (5) Among the 3 695 live births, 1 979 (53.6%) were delivered by cesarean section and 1 716 (46.4%) by vaginal delivery; 3 633 (98.3%) survived and 62 (1.7%) died in the neonatal period. The survival rate of newborns in the improved group was higher than that in the baseline group [98.8% (1 648/1 668) vs. 97.9% (1 985/2 027), χ2=4.23, P=0.040]. Among the 62 dead newborns, 51 (82.3%) had fatal structural or chromosomal abnormalities. (6) In the surviving neonates, 372 (10.2%) showed no abnormalities in a postnatal reexamination, and 468 (12.9%) received surgical treatment in the neonatal period. The other 2 793 cases received no treatment in the neonatal period but were followed up regularly. Conclusion:The optimized prenatal multidisciplinary consultation mode effectively reduces the rate of pregnancy termination due to non-fatal single structural malformations and increases the survival rate of newborns.

Objective:To investigate the clinicopathological factors and clinical significance of (micro)metastasis in No.12b lymph node in patients with gastric antrum cancer.Methods:This was a retrospective cohort study of data of 242 patients with gastric adenocarcinoma without distant metastasis, complete follow-up data, and no preoperative anti-tumor therapy or history of other malignancies. All study patients had undergone radical gastrectomy (at least D2 radical range) + No.12b lymph node dissection in the Department of Gastric Surgery of Liaoning Cancer Hospital from January 2007 to December 2012. Immunohistochemical staining with antibody CK8/18 was used to detect micrometastasis to lymph nodes. Patients with positive findings on hematoxylin and eosin stained specimens and/or CK8/18 positivity in No.12b lymph node were diagnosed as having No.12b (micro)metastasis and included in the No.12b positive group. All other patients were classified as 12b negative. We investigated the impact of No.12b (micro)metastasis by comparing the clinicopathological characteristics and recurrence free survival (RFS) of these two groups of patients and subjecting possible risk factors to statistical analysis.Results:Traditional hematoxylin-eosin staining showed that 15/242 patients were positive for No.12b lymph nodes and 227 were negative. A total of 241 negative No. 12b lymph nodes were detected. Immunohistochemical testing revealed that seven of these 241 No.12b lymph nodes (2.9%) were positive for micrometastasis. A further seven positive nodes were identified among the 227 nodes (3.1%) that had been evaluated as negative on hematoxylin–eosin-stained sections. Thus, 22 /242 patients' (9.1%) No.12b nodes were positive for micrometastases, the remaining 220 (90.9%) being negative. Factor analysis showed that No.12b lymph node (micro) metastasis is associated with more severe invasion of the gastric serosa (HR=3.873, 95%CI: 1.676-21.643, P=0.006), T3 stage (HR=1.615, 95%CI: 1.113-1.867, P=0.045), higher N stage (HR=1.768, 95%CI: 1.187-5.654, P=0.019), phase III of TNM stage (HR=2.129, 95%CI: 1.102-3.475, P=0.046), and lymph node metastasis in the No.1/No.8a/No.12a groups (HR=0.451, 95%CI: 0.121-0.552, P=0.035; HR=0.645, 95%CI:0.071-0.886, P=0.032; HR=1.512, 95%CI: 1.381-2.100, P=0.029, respectively). Survival analysis showed that the 5-year RFS of patients in the No.12b positive group was worse than that of those in the No.12b negative group (18.2% vs. 34.5%, P<0.001). Independent predictors of RFS were poorer differentiation of the primary tumor (HR=0.528, 95%CI:0.288-0.969, P=0.039), more severe serous invasion (HR=1.262, 95%CI:1.039-1.534, P=0.019), higher T/N/TNM stage (HR=4.880, 95%CI: 1.909-12.476, P<0.001; HR=2.332, 95%CI: 1.640-3.317, P<0.001; HR=0.139, 95%CI: 0.027-0.713, P=0.018, respectively), and lymph node metastasis in the No.12a/No.12b group(HR=0.698, 95%CI:0.518-0.941, P=0.018; HR=0.341, 95%CI:0.154-0.758, P=0.008, respectively). Conclusion:Detection of micrometastasis can improve the rate of positive lymph nodes. In patients with gastric antrum cancer, dissection of group No.12b lymph nodes may improve the prognosis of those with intraoperative evidence of tumor invasion into the serosa, more than two lymph node metastases, and suspicious lymph nodes in groups No.1 / No.8a / 12a.

Objective To investigate the impact of dexamethasone(DEX)on diaphragmatic atrophy caused by acute respiratory distress syndrome(ARDS)and its correlation with diaphragmatic protein metabolism.Methods Twenty healthy male Sprague-Dawley(SD)rats were randomly assigned to control,ARDS model,low-dose DEX,and high-dose DEX group,with each group consisting of five rats.ARDS was induced in the rats by intratracheal administration of lipopolysaccharide(LPS)at 4 mg/kg.Conversely,intratracheal saline was administered to the control group at 2 mL/kg.Following the induction of the model,an intraperitoneal injection of DEX at 1 mg·kg-1·d-1 was administered to the low-dose DEX group.Conversely,DEX at 5 mg·kg-1·d-1 was administered to the high-dose group for 7 consecutive days.Subsequently,on the eighth day of the experiment,the diaphragmatic weight of all rats was measured.Real-time quantitative polymerase chain reaction(PCR)was utilized to assess the mRNA expression of interleukins(IL-1β,IL-18)in each group.Western blotting was employed to determine the protein expression levels of nuclear factor-κB(NF-κB)p65,NOD-like receptor protein 3(NLRP3),caspase-1,Gasdermin D(GSDMD),myosin heavy chain 2(Myh2),and F-box protein 32(Fbxo32).Additionally,immunohistochemistry was utilized to evaluate the ratio of fast to slow muscle fibers in the diaphragm.Results The ARDS model group showed significant reductions in body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression compared to the control group[body weight(g):266±17 vs.292±15,diaphragm weight(g):0.77±0.02 vs.0.92±0.08,fast muscle fibers:(74±1)%vs.(78±3)%,Myh2 protein expression(Avalue):0.75±0.07 vs.0.95±0.05,all P<0.05].Conversely,significant increases were observed in the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32[IL-1β mRNA(IL-1β/GAPDH):2.2±0.3 vs.1.0±0.2,IL-18 mRNA(IL-18/GAPDH):2.3±0.3 vs.1.0±0.3,slow muscle fibers:(26±1)%vs.(22±3)%,NF-κB p65 protein expression(A value):0.40±0.15 vs.0.17±0.05,NLRP3 protein expression(A value):0.51±0.05 vs.0.27±0.08,caspase-1 protein expression(A value):0.54±0.12 vs.0.30±0.19,GSDMD protein expression(A value):0.40±0.12 vs.0.20±0.05,Fbxo32 protein expression(A value):0.51±0.15 vs.0.33±0.08,all P<0.05].Compared with the ARDS group,both low and high doses of DEX were found to further reduce body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression,and further increase the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32,with the changes in the high dose DEX group being more significant than those in the low dose group[body weight(g):198±14 vs.222±16,diaphragm weight(g):0.57±0.04 vs.0.68±0.04,fast muscle fibers:(56±5)%vs.(69±2)%,Myh2 protein expression(A value):0.29±0.16 vs.0.57±0.15,IL-1βmRNA expression:5.6±1.4 vs.3.3±0.6,IL-18 mRNA expression(IL-18/GAPDH):5.8±1.2 vs.3.9±0.6,slow muscle fibers:(44±5)%vs.(31±2)%,NF-κB p65 protein expression(A value):0.87±0.04 vs.0.70±0.07,NLRP3 protein expression(A value):0.75±0.08 vs.0.63±0.04,caspase-1 protein expression(A value):0.99±0.06 vs.0.82±0.08,GSDMD protein expression(Avalue):0.85±0.11 vs.0.61±0.10,Fbxo32 protein expression(Avalue):1.00±0.10 vs.0.78±0.12,all P<0.05].Normal muscle fiber structure was revealed by microscopic observation in the control group,clear fiber separation in the ARDS model group,and disordered muscle fiber arrangement with structural distortion was noted in both low and high-dose DEX groups.Conclusion Prolonged administration of DEX may worsen diaphragmatic atrophy induced by ARDS,possibly by promoting the activation of the NLRP3 inflammasome and cell pyroptosis.