Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Objective To investigate the frailty status and influencing factors of the elderly stroke pa-tients in community to provide a basis for its prevention and treatment.Methods The convenience sampling was used to select 200 elderly stroke patients as the study subjects in a community hospital in Guangzhou City from October 2020 to January 2022.The general information questionnaire,Chinese version of Tilburg frailty indicator scale,Modified Rankin Index Scale,Barthel index scale,short version of Geriatric Depression Scale and Social Support Rating Scale were used to collect the data.Results The incidence rate of frailty in 200 ca-ses of community elderly stroke was 86.0％.The results of multiple linear regression analysis showed that the degree of disability,ability of daily living,depression and social support were the influencing factors of frailty of the elderly stroke patients in community(F=71.813,P＜0.001).Conclusion The incidence rate of frailty is higher in community elderly stroke patients,the higher the degree of disability,the lower the ability of daily living,the higher the level of depression and the lower the level of social support,the higher the frailty level of community elderly stroke patients.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

Objective:To investigate the clinical and pathological characteristics of adrenocortical carcinoma (ACC) patients, and to analyze the correlation between clinical features and Ki-67 index.Methods:Retrospectively analyze the clinical data of ACC patients admitted into Peking Union Medical College Hospital from January 1984 to January 2024. Inclusion criteria: ①The patient underwent puncture or surgery, and was diagnosed as ACC; or those who had typical manifestations of adrenocortical multi-band disorders, extremely high FDG uptake in the adrenal area and distant metastasis, and the diagnosis of ACC was considered after multidisciplinary consultation in our hospital; ②The patient had undergone thoracic, abdominal and pelvic CT scan, and could determine the size of the tumor and whether metastasis occurred. Exclusion criteria: ①without pathological diagnosis of ACC or no diagnosis of ACC without multidisciplinary consultation in our hospital; ②no records of symptoms, signs, examinations and other information at the time of initial diagnosis. The baseline data (age, gender, tumor side, etc.), clinical manifestations, endocrine examination, imaging and pathological examination results of the patients were collected, and the relationship between the maximum tumor diameter, the stage of the European Network for the Study of Adrenal Tumors (ENSAT), the functional status of the tumor, the maximum uptake value of 18F-FDG (SUVmax) and the Ki-67 index was analyzed. Results:A total of 164 patients were included in this study. There were 65 males and 99 females, with a male to female ratio of 1∶1.52. The median age at diagnosis was 48 (40, 58) years old. 71 tumors were located (43.29%) on the left side with 91 cases (55.49%) on the right side, and 2 cases (1.22%) on both sides. The median tumor diameter was 9 (7, 12) cm, of which 147 cases (147/158, 93.04%) were>5 cm. A total of 162 patients had ENSAT stages, including 9 stages Ⅰ(5.56%), 72 stage Ⅱ (44.44%), 51 stage Ⅲ (31.48%) and 30 stage Ⅳ(18.52%), respectively. Among the 154 cases with evaluable symptoms, 101 had no typical clinical manifestations and 53 patients had typical clinical manifestations. There were 41 cases (26.62%) of Cushing syndrome, 36 (23.38%) cases of abnormal sexual characteristics, and 19 cases (12.34%) of primary aldosteronism. 100 patients (64.94%) had abnormal endocrine examinations. The results of pathological examination showed 138 cases (90.20%) of traditional subtype, 13 cases (8.50%) of eosinophilic subtype, 1 case of mucinous type (0.65%) and 1 case of sarcomatoid ACC (0.65%). The detection rate of intravascular tumor thrombus was 14.63% (24/164), and the inferior vena cava and renal vein thrombus (10.37, 17/164) were the most common. The median Ki-67 index was 20% (10%, 40%), and 93.13% (122/131) had a Ki-67 index higher than 5%. The median Ki-67 index of ENSAT stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 20%(10%, 35%), 15%(10%, 30%), 30%(20%, 60%), 30%(20%, 60%), respectively. Compared with stage Ⅱ, ENSAT stage Ⅲ ( P=0.0007) and stage Ⅳ ( P=0.0011) ACC had a higher Ki-67 index; there was no statistical correlation between Ki-67 index and tumor maximum diameter, SUVmax of the primary lesion, and functional status of tumor (all P>0.05). Conclusions:ACC has the characteristics of late staging upon initial diagnosis, low proportion of patients with typical symptoms, and low detection rate of intravascular tumor thrombus. ENSAT stage was correlated with the Ki-67 index. Compared with Stage Ⅱ, ENSAT stage Ⅲ and Ⅳ ACC had a higher Ki-67 index.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective:To explore the value of nuclear proliferation index (MIB-1) in the diagnosis and prognosis of adrenal cortical carcinoma (ACC).Methods:A retrospective analysis was conducted on the clinical data of ACC patients and patients with benign adrenal lesions admitted to Beijing Union Medical College Hospital from June 2018 to August 2022. There were 59 cases in the ACC group, 25 males and 34 females, with a male to female ratio of 1∶1.4. Age (46.1 ± 2.1) years old, including 4 cases under 20 years old, 7 cases between 21-30 years old, 11 cases between 31-40 years old, 14 cases between 41-50 years old, 13 cases between 51-60 years old, 8 cases between 61-70 years old, and 2 cases over 70 years old. Body mass index (24.3 ± 2.4) kg/m 2. Systolic blood pressure (149.3 ± 5.2) mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure (93.4±1.7) mmHg. There were 51 cases of typical Cushing's syndrome, 52 cases of hypertension, 44 cases of elevated blood sugar, 16 cases of hypokalemia, and 16 cases of menstrual abnormalities and acne caused by androgen secretion. Laboratory examination: Blood glucose (7.2 ± 0.3) mmol/L, glycated hemoglobin (8.6 ± 1.4)%, total cholesterol (5.7 ± 0.3) mmol/L, and triglycerides (2.0 ± 0.3) mmol/L. 24-hour urine free cortisol (234.4 ± 39.0)μg/24 h, with 46 cases showing an increase, and at 8am, corticotropin releasing hormone (9.5 ± 4.1) pg/ml, with 48 cases showing a decrease. Blood free cortisol (401.2 ± 17.1)μg/dl, with 42 cases of rhythm disappearance. 17 cases showed elevated aldosterone levels. Dehydroepiandrosterone sulfate (713 ± 159)μg/dl, of which 16 cases increased. Neuroenolase (21.2 ± 5.3) ng/ml, of which 27 cases were elevated. Insulin like growth factor-1 was (272.0 ± 42.1) ng/ml, with 26 cases showing an increase. 46 routine high-dose and low-dose dexamethasone inhibition tests were not suppressed. 39 cases of tumors were functional. 59 cases underwent preoperative abdominal and pelvic contrast-enhanced CT, MRI, and B-ultrasound examination, and 21 cases underwent PET/CT examination. The tumors were located in 32 cases on the left, 26 cases on the right, and 1 case on both sides. The maximum diameter of the tumor was (9.6 ± 1.7) cm, with 43 cases ≤10 cm and 16 cases >10 cm. There were 5 cases with lymph node metastasis, 16 cases with distant metastasis, and 11 cases with local invasion. There were 4 cases of tumor ENSAT clinical staging stage Ⅰ(T 1N 0M 0 stage), 27 cases of stage Ⅱ(T 2N 0M 0 stage), 23 cases of stage Ⅲ(T 1-2N 1M 0 stage, T 3N 0M 0 stage), and 5 cases of stage Ⅳ(T 1-4N 0-1M 1 stage, T 3N 1M 0 stage, T 4N 0-1M 0 stage). Six cases were accompanied by tumor thrombi in the central adrenal vein, renal vein, and inferior vena cava. There were 53 cases of benign adrenal tumors, including 26 males and 27 females. Age (44.3±3.2) years old, typical manifestations of Cushing's syndrome in 28 cases, 24-hour urine free cortisol (176.4±41.2) μg/24 h. 27 cases showed disappearance of free cortisol rhythm. Dehydroepiandrosterone sulfate is normal. 23 routine high-dose and low-dose dexamethasone inhibition tests were not inhibited. The maximum diameter of the tumor is (4.2 ± 2.3) cm. T 1N 0M 0 stage patients undergo robotic or laparoscopic radical adrenalectomy, with the resection range including the surrounding lymphoid tissue of the tumor; Patients with stage ≥T 2 underwent open radical adrenalectomy and lymph node dissection. Six cases underwent radical adrenalectomy combined with nephrectomy due to tumor invasion of the kidneys with unclear boundaries. 11 cases of local implant metastasis underwent stereotactic radiotherapy. Nine patients with liver metastasis underwent Interventional Embolization treatment. Three cases with isolated lung metastases underwent surgical resection. Four cases of multiple lung metastases were treated with radiotherapy combined with mitotane. According to the postoperative pathological examination results, record the pathological Weiss score and MIB-1. Analyze the correlation between MIB-1 and clinical pathological indicators and prognosis of patients. Results:There were 59 cases in the ACC group, 35 cases of R0 resection, 19 cases of R1 resection and 5 cases of R2 resection.The postoperative pathological examination showed an average weight of approximately (371±52)g, with 42 cases having a tumor mass ≤ 300 g and 17 cases having a tumor mass>300 g. The positive rate of MIB-1 in the control group was 1% to 5%, while the positive rate of MIB-1 in the ACC group was greater than 5%, the difference between the two groups was statistically significant ( P<0.01). 53 patients diagnosed with capsule invasion, capsule rupture, intravascular tumor thrombus, and MIB-1>10% through postoperative pathological examination were treated with tumor bed radiotherapy and mitotan medication, followed by second-line combination immunotherapy and EDP chemotherapy. The 5-year survival rates of ACC patients with different tumor stages were 65% in stage Ⅰ, 58% in stage Ⅱ, 38% in stage Ⅲ, and less than 5% in stage Ⅳ. The total survival time of the two subgroups with low and high staging was 3.6 years and 1.1 years respectively ( P=0.003), while the disease-free survival time of the two groups was 25 months and 11 months, respectively ( P=0.011). R0 resection has a better prognosis than R1 and R2 resection, and its five-year survival rate is higher ( P=0.03). The 5-year survival rates of R0, R1, and R2 groups were 61%, 31%, and 17%, respectively( P=0.030).Survival analysis showed that adrenal cortical cancer patients with MIB-1 greater than 10% had a worse prognosis, with 5-year OS of 17% and 32% for both groups, respectively ( P=0.021). The Weiss score of the ACC group was (7±2). There were 21 cases in the Weiss score 3-5 group and 38 cases in the 6-9 group, the 5-year survival rates of the two groups were 62% and 19%, respectively ( P=0.017). Conclusions:MIB-1 can serve as an auxiliary diagnostic and prognostic indicator, and high expression of MIB-1 can contribute to the early diagnosis and determination of treatment strategies for ACC.

Objective To explore the magnetic resonance imaging(MRI)manifestations of acute cerebral infarction(ACI)and the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2),cystatin C(Cys C)and short-term prognosis.Methods A total of 110 ACI patients admitted to the department of neurology in our hospital from January 1,2022 to January 1,2023 were selected as the study objects.The clinical data and multimodal MRI were collected,and the serum Lp-PLA2 and Cys C levels of patients were detected.The patients were divided into the good prognosis group and the poor prognosis group according to the modified Rankin scale(mRS)score 90 days after onset.The predictive value of MRI manifestations and Lp-PLA2 and Cys C levels for short-term poor prognosis was analyzed.Results There were statistically significant differences in the time from onset to admission,National Institute of Health Stroke Scale(NIHSS)score on admission,hypertension or diabetes,coronary heart disease or atrial fibrillation of patients between the good prognosis group and the poor prognosis group(P<0.05).The proportions of patients with ischemic penumbra,HV positive,cortical-subcortical infarction,large perforating branch infarction,small perforating branch infarction,bilateral anterior circulation infarction,posterior circulation infarction,anterior-posterior circulation infarction,middle cerebral artery(MCA)stenosis or occlusion,both internal carotid artery(ICA)and MCA stenosis or occlusion,posterior cerebral artery(PCA)or vertebral artery(VA)stenosis or occlusion and hemorrhage transformation in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).The Lp-PLA2 and Cys C levels of patients in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).Small penetrating branch infarction,posterior circulation infarction,anterior-posterior circulation infarction,MCA stenosis or occlusion,both ICA and MCA stenosis or occlusion,hemorrhage transformation,serum Lp-PLA2 and Cys C had certain predictive value for patients with short-term poor prognosis(P<0.05).Conclusion MRI manifestations(ischemic penumbra,HV positivity,different types of cerebral infarction,and vascular stenosis)and serum Lp-PLA2 and Cys C levels can predict the short-term prognosis of ACI patients and provide important reference for the formulation of clinical treatment plans.