Objective To explore the evaluation value of forkhead box M1(FOXM1)and CC chemokine receptor 5(CCR5)on lung function and prognosis in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 128 AECOPD patients admitted to Yueyang People's Hospital from January 2022 to January 2023 were collected as the acute exacerbation group,135 stable COPD patients admitted at the same time were regarded as the stable phase group,and 120 health examination volunteers of similar age and gender were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression levels of FOXM1 and CCR5 in serum,and the vital capacity meter was applied to measure pulmonary function.Pearson method was applied to analyze the correlation between serum FOXM1,CCR5 and lung function indicators in AECOPD patients.Multivariate logistic regression analysis was applied to screen prognostic factors for AECOPD patients.The evaluation value of FOXM1 and CCR5 levels in evaluating poor prognosis of AECOPD patients was analyzed by receiver operating characteristic(ROC)curve.Results In the serum of patients in the AE COPD group and stable stage group,the levels of CCR5(49.36±12.31 ng/ml,34.25±8.87 ng/ml)and FOXM1(40.21±10.74 pg/ml,23.38±5.77 pg/ml)were significantly higher than those in the control group(14.55±4.58 ng/ml,15.06±3.55 pg/ml),while FEV1(1.15±0.13 L,1.67±0.19 L),FVC(2.93±0.30 L,3.28±0.36 L)and FEV1/FVC(39.25％±3.97％,50.91％±5.01％)were lower than those in the control group(1.95±0.26 L,3.57±0.44 L,54.62％±5.20％),with significant differences(F=11 1.034～641.907,all P＜0.05).The levels of serum FOXM1 and CCR5 were gradually increased with the aggravation of lung function grading,while the levels of lung function indicators FEV1 and FVC were gradually decreased with the aggravation of lung function grading,and the differences were statistically significant(F=31.27,49.37;42.72,29.48,all P＜0.05).The serum levels of FOXM1 and CCR5 were negatively correlated with FEV1,FVC and FEV1/FVC(r=-0.639～-0.479,all P＜0.05).Logistic regression analysis found that CCR5[OR(95％CI):3.380(1.944～5.876)],FOXM1[OR(95％CI):5.711(3.175～10.273)],APACHE Ⅱ score[OR(95％CI):2.132(1.243～3.660)],and lung function grading[OR(95CI):2.017(1.007～4.037)]were all risk factors for poor prognosis(all P＜0.05),while FEV1[OR(95％CI):0.649(0.441～0.955)]and FVC[OR(95％CI):0.120(0.073～0.198)]were protective factors for poor prognosis(all P＜0.05).ROC curve results showed that the areas under the curve(AUC)of serum FOXM1 and CCR5 levels in predicting poor prognosis in AECOPD patients were 0.821 and 0.831,respectively.The AUC predicted by the combination of the two was 0.895,which was higher than that detected by a single indicator(Z=2.800,2.654,all P＜0.05).Conclusion FOXM1 and CCR5 were both high levels in the serum of AECOPD patients.Early detection of them can serve as serum markers for evaluating lung function and poor prognosis in AECOPD patients.

Objective:To evaluate the effects of intrathecal infusion chemotherapy on intracranial pressure (ICP) in non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM) by ultrasound measurement of the optic nerve beside the bed of optic nerve sheath diameter (ONSD) .Methods:A total of 31 NSCLC-LM patients who underwent intrathecal infusion chemotherapy at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from June 10, 2021 to December 25, 2022 were collected. The ONSD values were measured before and after the first lumbar puncture by bedside optic nerve ultrasound, and measured dynamically 30 min before intrathecal infusion chemotherapy (T0) , 30 min (T1) , 1 h (T2) , 2 h (T3) , 4 h (T4) , 6 h (T5) , and 24 h (T6) after intrathecal infusion chemotherapy. ICP ONSD was calculated, with differences between ICP LP and ICP ONSD, and differences between ONSD and ICP ONSD series at different time being compared separately. Mean arterial pressure (MAP) , heart rate, and headache score were assessed and compared respectively at T0, T1, T2, T3, T4, T5 and T6. Spearman analysis was used to evaluate the correlation between the response assessment in neuro-oncology (RANO) score and ICP. Results:Before the first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (218.55±63.83) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (217.28±57.17) mmH 2O, (223.64±51.13) mmH 2O, and (220.46±52.50) mmH 2O respectively, in NSCLC-LM patients, with no statistically significant difference ( F=0.77, P=0.463) . After first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (214.68±58.01) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (216.71±48.96) mmH 2O, (216.62±47.18) mmH 2O, and (216.67±47.86) mmH 2O respectively, with no statistically significant difference ( F=0.12, P=0.757) . At T0, T1, T2, T3, T4, T5, and T6, the MAP during intrathecal infusion chemotherapy was 89.80 (83.40, 93.67) mmHg, 95.00 (80.83, 99.37) mmHg, 91.86 (79.88, 100.14) mmHg, 90.15 (79.04, 100.55) mmHg, 105.14 (88.55, 114.74) mmHg, 98.96 (81.72, 111.81) mmHg, and 89.29 (85.45, 100.38) mmHg, with a statistically significant difference ( χ2=16.11, P=0.013) ; heart rates were 80.00 (75.00, 84.50) times/min, 80.00 (72.50, 87.50) times/min, 74.00 (66.00, 87.50) times/min, 82.00 (72.00, 90.00) times/min, 80.00 (70.50, 90.00) times/min, 77.00 (68.00, 91.00) times/min, 77.00 (71.50, 88.50) times/min, with no statistically significant difference ( χ2=2.18, P=0.902) ; headache scores were 2.00 (0.50, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (2.00, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (1.00, 2.00) score, 2.00 (1.00, 2.00) score, and 2.00 (0.00, 2.00) score, with no statistically significant difference ( χ2=11.64, P=0.071) . At T0, T1, T2, T3, T4, T5, and T6, left eye, right eye, and binocular ONSD were (5.85±0.64) mm, (5.72±0.68) mm, (7.11±1.11) mm, (6.42±0.78) mm, (5.69±0.63) mm, (5.61±0.64) mm, (5.65±0.88) mm, (5.85±0.12) mm, (5.89±0.12) mm, (6.93±0.20) mm, (6.40±0.14) mm, (5.71±0.12) mm, (5.66±0.12) mm, (5.33±0.14) mm, (5.85±0.64) mm, (5.81±0.64) mm, (7.02±1.03) mm, (6.41±0.75) mm, (5.70±0.63) mm, (5.64±0.63) mm, (5.49±0.76) mm, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.05, P<0.001) ; ICP ONSD were (222.81±56.81) mmH 2O, (211.89±60.29) mmH 2O, (335.12±98.32) mmH 2O, (274.17±68.87) mmH 2O, (208.77±56.12) mmH 2O, (201.75±56.79) mmH 2O, (205.59±78.36) mmH 2O, (223.26±58.33) mmH 2O, (227.08±61.68) mmH 2O, (319.36±101.10) mmH 2O, (272.33±69.61) mmH 2O, (211.21±57.73) mmH 2O, (206.51±57.22) mmH 2O, (177.22±68.98) mmH 2O, (223.03±57.24) mmH 2O, (219.49±57.24) mmH 2O, (327.24±91.56) mmH 2O, (273.25±67.04) mmH 2O, (209.99±56.26) mmH 2O, (204.13±56.29) mmH 2O, (191.40±67.95) mmH 2O, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.13, P<0.001) . The ONSD of the left eye, right eye, and binocular eyes and the corresponding ICP ONSD increased significantly at T2 compared with T0, T1, T3, T4, T5, and T6, with statistically significant differences (all P<0.05) . Pre- and post-treatment RANO scores were 4.00 (3.00, 7.00) score and 3.00 (2.00, 6.00) score respectively. Pre- and post-treatment RANO scores were positively correlated with ICP ONSD in the left eye ( r=0.55, P=0.001; r=0.60, P<0.001) , right eye ( r=0.54, P=0.001; r=0.46, P=0.009) and binocular eyes ICP ONSD ( r=0.45, P=0.010; r=0.37, P=0.043) . Conclusion:Intrathecal infusion chemotherapy for NSCLC-LM patients can cause a transient increase in ONSD and ICP, with the greatest effect at 1 hour after intrathecal infusion chemotherapy. RANO score is positively correlated with ICP ONSD before and after treatment, which can provide an important reference for evaluating the efficacy of intrathecal infusion chemotherapy.

Objective:To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis (LM) from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.Methods:A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital, Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected, and divided into 30, 40 and 50 mg groups ( n=10, n=4, n=7) according to pemetrexed dose. Cerebrospinal fluid was collected at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy, and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid, to clarify the drug-related pharmacokinetic parameters, and to compare the differences in pemetrexed concentration among groups. Finally, cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results:There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy (30 mg group: F=20.56, P<0.001; 40 mg group: F=27.06, P<0.001; 50 mg group: F=28.63, P<0.001), and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5, 1, 2, 4, 6 and 12 h compared to 0 h after intrathecal injection chemotherapy (all P<0.05). Compared to the 30 mg group, cerebrospinal fluid drug concentrations in the 50 mg group increased at 1, 2, 4, 6, 12 and 24 h after intrathecal injection chemotherapy, with statistically significant differences (all P<0.05). Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve (AUC) 0-∞ of the 30, 40 and 50 mg groups were (5 696.12±283.32), (7 886.29±396.57), and (14 202.70±440.19) h·mg/L, respectively, with a statistically significant difference ( F=1 159.00, P<0.001) ; AUC 0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; AUC 0-∞ increased in the 40 mg group compared to the 30 mg group ( P<0.05). The half-lives of three groups were (8.75±0.23), (11.29±0.59) and (16.42±1.23) h, respectively, with a statistically significant difference ( F=206.80, P<0.001) ; half-life was longer in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; half-life was longer in the 40 mg group compared to the 30 mg group ( P<0.05). The peak time of three groups were (1.55±0.10), (1.00±0.01), (1.43±0.11) h, respectively, with a statistically significant difference ( F=48.11, P<0.001) ; the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group (both P<0.05). Clearance of three groups were (7.02±2.46), (5.80±1.25) and (3.66±1.32) L/h, respectively, with a statistically significant difference ( F=6.02, P=0.009) ; clearance was decreased in the 50 mg group compared to the 30 mg group ( P<0.05). The peak concentration of three groups were (540.45±32.25), (820.75±46.47) and (1 014.78±64.96) mg/L, respectively, with a statistically significant difference ( F=207.70, P<0.001) ; peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; peak concentration increased in the 40 mg group compared to the 30 mg group ( P<0.05). Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy, in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were (13.76±4.79), (11.41±7.08), (9.41±2.59) and (7.86±4.02) mg/L, respectively; 40 mg group were (14.45±6.59), (12.87±15.73), (11.24±2.48) and (9.09±3.38) mg/L, respectively; 50 mg group were (12.94±10.34), (9.72±7.62), (8.15±8.17) and (4.34±4.21) mg/L, respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group ( F=4.04, P=0.016), and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 (both P<0.05). There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups ( F=0.28, P=0.837; F=3.57, P=0.066) . Conclusion:Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid; dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma.

Objective:To study the efficacy of different surgical methods in treatment of hilar cholangiocarcinoma (HCCA), and to analyze the factors affecting long-term prognosis of HCCA patients after surgical treatment.Methods:The clinical data of 105 patients who underwent surgical treatment for HCCA at the First Affiliated Hospital of Soochow University from April 2010 to October 2021 were retrospectively analysed. There were 58 males and 47 females, with age (64.2±10.6) years old. Data analysed included surgical treatments, postoperative pathological data, perioperative complications and survival on follow-up. The Kaplan Meier survival curve was plotted, and the log-rank test and Cox proportional hazard model were performed to analyze the key factors affecting long-term prognosis.Results:Of 105 patients, 4 (3.8%) patients died during the perioperative period, and 58 patients (55.2%) developed complications with included 32 (30.5%) patients with pleural effusion and 12 (11.4%) patients with biliary leakage. The follow-up data was available in 85 patients with the overall median survival time of 19 months, and the 1-, 3-, 5-year cumulative survival rates of 58.1%, 27.0% and 24.8% respectively. The 1-, 3-, and 5-year cumulative survival rates for the R 0 resection patients ( n=59) were 69.4%, 36.2%, 27.4%, respectively, which were significantly better than 49.4%, 12.3%, 0% for the R 1/2 resection patients ( n=20), and 0% for the palliative drainage patients ( n=6) (all P<0.05). Univariate analysis and Cox multivariate analysis showed that age ≥70 years ( HR=2.158, 95% CI: 1.175-3.965), preoperative CA19-9 level ≥1 015 U/ml ( HR=1.981, 95% CI: 1.009-3.894), resection margin ( HR=2.587, 95% CI: 1.371-4.881), and lymph node metastasis ( HR=2.308, 95% CI: 1.167-4.567) were independent risk factors for long-term prognosis of HCCA patients (all P<0.05). Conclusions:R 0 resection was an effective way to prolong survival of patients with HCCA. Age, preoperative CA19-9 level, resection margin and lymph node metastasis were related to long-term survival of HCCA patients.

ObjectiveTo understand the current situation and influencing factors of health service demands of new residents in Shanghai. MethodsFrom July to August 2020， a questionnaire survey was conducted in 1 358 new residents from 36 survey points in 7 districts of the city. The questionnaire included the basic medical insurance coverage in the inflow area， the current situation of medical demand and related influencing factors， and the demands for other health services. Results47.1%（562/1 194）of new residents did not choose to seek timely medical treatment when they were not feeling well. The main reason was that the working hours occupied the medical treatment time. Logistic regression analysis showed that the main factors affecting the medical needs in new residents were the average daily working hours， living area and type of residence， health status， physical examination and physical exercise， and the type of basic medical insurance. The demands of new residents for "health consultation of common diseases and frequently occurring diseases"， "health behavior intervention （such as smoking cessation and alcohol restriction）"， "medical guidance and publicity"， "accidental injury prevention （traffic， work， falling， etc.）" and "maintenance of legitimate rights and interests of health" were 57.1%（682/1 194）、41.3%（493/1 194）、34.9%（417/1 194）、32.2%（385/1 194） and 31.9%（381/1 194）， respectively. ConclusionNew residents demands for medical services cannot be met. We should actively improve the working and living conditions of new residents， improve the construction of new residents' health service system， and improve the utilization level of health services.

In recent years, society has gradually shifted from a "fearful" approach of unscientific plan design, unbalanced resource protection and inadequate management experience leading to the spread of public panic and negative emotions to a "comfortable" approach of proactive prevention, precise control, information symmetry, scientific response and systematic treatment in the face of public health emergencies. College students are increasingly becoming the "key minority" to participate in crisis management. This is mainly due to their values in line with social ideals, their mobility in line with disciplinary practice and volunteerism, their knowledge accumulation in multi-disciplinary cross-fertilization, and their good cognitive thinking literacy, high information media literacy and perfect social support system. Therefore, this group has a strong comprehensive advantage in public health emergencies. Based on this background, combined with on-site investigation and interview feedback, this paper considered that this group can play an active role in normal prevention and early warning beforehand, information transmission and communication at the moment the event occur, corrective cognitive implementation and disposal in the event, and scientific research innovation and popularization afterwards, so as to better play an increasingly important leading demonstration effect in public health emergencies. At the same time, it can also encourage universities to take the initiative in the process of talent training to teach people according to the concept of "change according to the matter, advance according to the time and new according to the situation", and lead college students of different majors to maximize the pioneering effect of role models in public health emergencies.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Objective:To screen for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlations.Methods:To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR, Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) in probands and families of BPES from January 2018 to January 2021, obtain mutation sites of pathogenic genes.Results:4 BPES families (8 cases) including 4 males and 4 females, with age ranged form 4 to 52 years (mean 24). The proband of family 1 has fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene. Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene. There are missense mutations of c. 241 T>C(p.Y81 H)in proband and affected mother of family 3. There are c. 672_701dup(p.A224_A234dup) in-frame duplication mutations in proband and affected mother of family 4.Conclusions:Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Objective:To screen for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlations.Methods:To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR, Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) in probands and families of BPES from January 2018 to January 2021, obtain mutation sites of pathogenic genes.Results:4 BPES families (8 cases) including 4 males and 4 females, with age ranged form 4 to 52 years (mean 24). The proband of family 1 has fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene. Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene. There are missense mutations of c. 241 T>C(p.Y81 H)in proband and affected mother of family 3. There are c. 672_701dup(p.A224_A234dup) in-frame duplication mutations in proband and affected mother of family 4.Conclusions:Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

BACKGROUND: Leptomeningeal metastasis (LM) is one of the most common causes of death in patients with advanced non-small cell lung cancer (NSCLC), which is defined as malignant cells spreading to meninges and cerebrospinal fluid (CSF). Therefore, early diagnosis and timely treatment are essential. CSF cytology is the gold standard for LM diagnosis, however, it has a low sensitivity for diagnosis and can't be used to evaluate the treatment effect. The aim of this study was to assess the clinical value of serum and CSF tumor markers (TM) in the diagnosis and treatment of NSCLC patients with LM. METHODS: Nineteen patients with NSCLC-LM and 27 patients with nonmalignant neurological diseases (NMNDs) were included. We tested the levels and positive rates of carbohydrate antigen (CEA), carbohydrate antigen-125 (CA125), cytokeratin 19 fragments (CYFRA21-1) and neurone specific enolase (NSE) in CSF and serum, compared the sensitivity and specificity in the diagnosis of LM between different groups, and analyzed the correlation of detection between serum and CSF. Finally, we measured serum and CSF TM dynamically in 2 patients with NSCLC developing LM in an attempt to correlate these with the treatment response of extracranial and intracranial, respectively. RESULTS: The levels and positive rates of TM in CSF and serum in LM group were higher than those in NMNDs (P<0.05). In LM group, the levels of CEA, CYFRA21-1 and CEA were significantly higher in CSF than that in the serum (P<0.05), whereas, there was no statistical significance in positive rates of TM between CSF and serum (P>0.05). In CSF, CYFRA21-1 has the highest sensitivity (88.2%) and CEA has the best specificity (92.3%) to distinguish patients between LM and NMNDs. For combined detection of CEA, CA125, CYFRA 21-1 and NSE in CSF, when at least CEA or NSE was positive in patients with LM, the sensitivity and negative predictive value were 100.0%, and the specificity was 74.1%. When both CYFRA21-1 and NSE were positive, the specificity and positive predictive value were 100.0%, and the sensitivity was 78.9%. Furthermore, subgroup analysis showed that the detection rates of TM in CSF cytology positive population was higher than that in typical abnormalities magnetic resonance imaging population, but there was no statistical difference (P>0.05). The detection of TM between serum and CSF in LM patients had no significant correlation. Moreover, biochemical properties of CSF from ventricle and lumbar puncture are similar, therefore evaluating the levels of TM in serum and CSF dynamically can be used to assess the extracranial and intracranial treatment effect, respectively. CONCLUSIONS Our study demonstrates that Serum and CSF TM can work as an auxiliary clinical diagnostic tool, which has a potential value in early diagnosis of NSCLC patients with LM. Serial measurement of TM may play an important role in the clinical management of NSCLC patients with LM, which is worthy of further promotion and clinical application.