Objective To investigate the impact of total parathyroidectomy with autotransplantation (tPTx+AT)on bone mineral density and serum soluble Klotho (sKlotho)level in patients with secondary hyperparathyroidism (SHPT).Methods A total of 86 patients undergoing tPTx+AT in the Second Affiliated Hospital of Anhui Medical University from June 2019 to May 2022 were recruited in this study.Their demographic characteristics were collected before surgery,along with serum levels of corrected calcium,phosphorus,intact parathyroid hormone (iPTH),alkaline phosphatase (ALP),fibroblast growth factor 23 (FGF23),and sKlotho before and at 5 d,and 1,3,6,12 and 24 months after surgery.Dual energy X-ray absorptiometry was used to determine the BMD values of the lumbar spine L1-L4 before surgery and at 3,6,12 and 24 months after surgery.The changes in BMD and serum FGF23 and sKlotho levels before and after tPTx+AT were observed.Results Surgical treatment was successfully completed in all 86 patients,with their clinical symptoms such as bone pain and skin itching significantly improved postoperatively,and markedly decreased serum calcium,phosphorus,iPTH,ALP and FGF23 levels.The sKlotho level was significantly lower at 5 d postoperatively than that preoperatively,with that at 1 month after surgery increased by approximately 24.5％ than the preoperative level,and then the level was in a stable trend.The BMD values at the lumbar spine L1-L4 were increased postoperatively,and reached the highest levels at 12 months postoperatively.Further analyses showed that dialysis vintage,duration of SHPT,and ALP,iPTH and FGF23 levels were negatively correlated with the Z-scores of the lumbar spine L1-L4,while sKlotho level was positively correlated with the Z-scores.Conclusion tPTx+Atcan significantly improve the clinical symptoms of SHPT patients,regulate the balance of calcium and phosphorus metabolism,increase sKlotho level and reduce FGF23 level.It is an effective method to improve BMD.

Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.

Objective To study the relationship between ischemic stroke and gene polymorphism of an-giotensin-converting enzyme (ACE), apolipoprotein E (APOE) and methylene tetrahydrofolate reductase (MTHFR) among the population of Zhuang nationality in western Gui. Methods We directly sequenced ACE, APOE and MTHFR genes in 149 cases of ischemic stroke and 109 cases of normal people in western Gui. χ2 test was used to measure the relationship between gene polymorphism and ischemic stroke. Hardy-Weinberg genetic equilibrium test was used to evaluate the reliability of these data. Results In the ischemic stroke group, 62 cases, 22 cases and 65 cases carried II genetype, DD genetype and ID genetype in ACE. χ2 test showed no relationship between ACE gene polymorphism and ischemic stroke. In analysis of the polymorpism of APOE in the ischemic stroke and control group, no relationship between APOE gene polymorphism and ischemic stroke was found by χ2 test. MTFHR gene polymorphism was significantly related with ischemic stroke by χ2 test (P = 0.019). Conclusion Polymorphism of gene MTFHR but neither ACE nor APOE is significantly associated with ischemic stroke.

Abstrac Objective:To investigate the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of squamous-cell lung cancer patients with EGFR mutations. Methods:We screened out seven patients who were diag-nosed with EGFR mutations and received EGFR-TKIs, such as gifitinib or erlotinib, from 2,317 squamous-cell lung cancer patients treat-ed at the Beijing Chest Hospital from January 2010 to July 2016. Results:After using EGFR-TKIs, the objective response rate was 42.9%, the disease control rate was 100%, and the median progression-free survival was 6.1 months. Conclusion:EGFR-TKIs exert a certain clinical curative effect on patients with EGFR mutations in squamous-cell lung cancer. However, given that only seven cases are pre-sented in this research group, more cases are needed for further research to verify the above conclusion.

Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. hTe aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV) with EGFR mutations were ifrst-line treated with an oral administration of afatinib (40 mg/d) until disease progression. Adverse events, effects, and survival condition were observed. Results hTe most common adverse events were diarrhea (n=5, 100%), skin rash (n=4, 80%), and mucositis/stomatitis (n=4, 80%). Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. hTree patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%), one with stable disease (25%) and one with progressive disease (25%). Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afa-tinib was approved as ifrst-line treatment for patients with advanced lung adenocarcinoma. hTe most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for conifrmation.

Objective To describe the clinical features of invasive fungal disease in Huashan Hospital,Fudan University from January 2004 to December 2006.Methods The medical data were reviewed retrospectively for the patients with fungal infection, which was confirmed by positive fungal culture or microscopic examination with blood,sterile body fluid,deep tissue,sputum specimen or isolation of Aspergillus spp.and Cryptococcus spp.from bronchoalveolar lavage.The proven and probable cases of invasive fungal disease were included in this analysis.Results A total of 111 patients were diagnosed as invasive fungal dis-ease,including 104 proven cases and 7 probable cases.Sixty-one cases were community-acquired and the other 50 were nosoco-mial.The most common site of infection was bloodstream (51,45.9%),followed by central nervous system (44,39.6%)and respiratory system (14,12.6%).The most common pathogens were Candida spp.(50,45%),Cryptococcus (47,42.3%) and Aspergillus spp. (12, 10.8%). The community-acquired fungal infections were mostly found in central nervous system (44,72.1%),and respiratory system (12, 19.7%),mainly caused by Cryptococcus and Aspergillus. The nosocomial fungal infections occurred primarily in blood-stream (96.0%),mainly due to Candida spp.No underlying disease or risk factor was identified in more than half of the pa-tients with community-acquired infection,while almost all the patients with nosocomial fungal infection had underlying disease and predisposing factors.Indwelling venous catheter was closely associated with nosocomial bloodstream infection.Indwelling venous catheter lasted for more than 1 week in 64.7% of the patients with Candida bloodstream infection.The same fungal strain was isolated from both the cather and blood of the same patient in 11 cases.The overall mortality of these invasive fungal diseases was 14.4% (16/111).The mortality rate was 18.0% (9/50)in the patients with nosocomial invasive fungal infection, and 11.5% (7/61)in the patients with community-acquired invasive fungal infection.Conclusions The most common site of in-vasive fungal infection is bloodstream,followed by central nervous system,and respiratory system.Majority of the fungal patho-gens are Candida spp.,Cryptococcus and Aspergillus spp.The community-acquired invasive fungal disease is primarily meningitis caused by Cryptococcus.The nosocomial invasive fungal disease is mainly bloodstream infection caused by Candida spp.

Objective To investigated the efficacy and toxic effects of combined chemotherapy of vinorelbine plus cisplatin or carboplatin in patients aged ≥ 70 years and with non-small cell lung cancer (NSCLC).Methods One hundred patients with lung cancer aged ≥70 years were enrolled in the study.Fifty patients in chemotherapy group were assigned to receive vinorelbine 25 mg/m2 at the first day and the fifth day plus cisplatin 60-70 mg/m2 or carboplatin 250 mg/m2 at the second day.All treatments were repeated every 3 or 4 weeks.Another fifty patients aged ≥ 70 years were taken as control group, not receiving treatment.The primary endpoint was survival.Results Forty-five patients were evaluable for response and the partial remission rate was 35.6% (16/45).One year survival rate was 37.8% and median survival time was 9.75 months in chemotherapy group.The median survival time was 4.0 months for patients in control group.All 50 patients in chemotherapy group were evaluable for toxic side effects.WHO grade Ⅲ incidences of leucopoenia, neutropenia and anemia were 38.0%, 52.0% and 2.2%, respectively.Grade IV incidence of neutropenia was 35.5%.WHO grade Ⅲ incidences of fatigue, constipation and vomit were 22.0%, 8.0% and 14.8%,respectively.Five patients failed to complete the treatment due to side effects.Conclusions Combined chemotherapy of vinorelbine plus platinum drugs is effective and tolerated in patients aged over 70 years with advanced NSCLC.Even patients with stable clinical effects shows benefit of survival time.

BACKGROUNDUroacitides is a group of cell differentiation inducers, which is purified from fresh human urine. Preclinical studies of Uroacitides have showed that cancer cells could be induced to differentiate, and the growth of cancer cells could be inhibited by Uroacitides. The aim of this study is to compare the efficacy and toxicity between Uroacitides combined with NP regimen and NP alone in treatment of advanced non-small cell lung cancer (NSCLC).

METHODSForty-two cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP group: NVB 25mg/m² on days 1 and 8, DDP 75mg/m² on day 1. Uroacitides combined with NP group: Uroacitides of 300mL was given through subclavian catheter daily for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2 cycles, except the days of administration of chemotherapy.

RESULTSIn the Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP group and 6 months in the NP group (P=0.0287). The main toxicities were myelosuppression, gastrointestinal reaction and alopecia, and there was no significant difference in incidences of toxicities between the two groups (P > 0.05).

CONCLUSIONSUroacitides combined with NP regimen shows a good curative effect and low toxicity, and may significantly prolong the median survival time for advanced NSCLC.

BACKGROUNDGensing Rg3 is an active component from ginseng. The aim of this study is to observe the clinical anticancer effect of Rg3 in combination with chemotherapy regimen NP (vinorelbine+cisplatin) in advanced non-small cell lung cancer (NSCLC).

METHODSStage III-IV NSCLC patients confirmed by pathology or cytology all received vinorelbine plus cisplatin for at least two cycles, and were randomized into two groups: patients in arm A also received placebo twice a day, while patients in arm B received two tablets of Rg3 twice a day for at least two months. The endpoints of the study were the efficacy, survival and tolerance of patients.

RESULTSFrom July 2000 to May 2002, 115 patients were enrolled into the trial. The patients' characteristics were well balanced in the two groups. Sex of patients: male, 79; female 36. Types of pathology: adenocarcinoma, 71; squamous cell carcinoma, 29; adenosquamous carcinoma, 8; others, 7. TNM stage: stage III, 45; stage IV, 70. Prior chemotherapy: with, 17; without, 98. Prior radiotherapy: with, 15; without, 100. Prior surgical treatment: with, 23; without, 92. Nine patients discontinued from the trial due to severe adverse effects (5) and other reasons (4), so there were 106 patients evaluable for clinical efficacy. The response rate was 14.5% (8/55) in arm A, and 33.3% (17/51) in arm B (P=0.011). The survival time in arm A was 9.7 months (mean) and 8.0 months (median), and 15.3 months (mean) and 10.0 months (median) in arm B (P=0.0088).

CONCLUSIONSPreliminary results show improvements in response rate and survival time (median and mean) in Rg3 arm compared with placebo arm. It is worthy to confirm the results in further clinical trials.

BACKGROUNDTo evaluate the activity and toxicity of paclitaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC).

METHODSForty patients with recurrent advanced NSCLC were enrolled. Thirty-six patients were managed with regular regimen. Paclitaxel 135 mg/m², 3 h, on day 1; DDP 75 mg/m² or carboplatin 300-350 mg/m² on day 2. Four patients were managed with weekly regimen. Paclitaxel 60 mg/m²,3 h, on days 1,8,15; DDP 75 mg/m² on day 2. It was repeated every three or four weeks, up to two to four cycles.

RESULTSThirty-six cases were evaluated for response and 27 for survival. The objective response rate was 13.9% (5/36). At least one tumor-related symptom relief was observed in 21 patients (58.3%). The median survival duration was 26.4 weeks and 1-year survival rate was 8% (4/36). The main toxicities included myelosuppression, fatigue and myalgia-arthralgia neuropathy.

CONCLUSIONSPaclitaxel has advantage to be well-tolerated and improve tumor-related symptom. Further studies with standardization of dose and regimen will be needed to clarify its role in the second-line treatment.