ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease（PD）. MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group， with 30 patients in each group. The control group received levodopa only， starting at 100 mg per dose， three times daily， with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment， after 6 and 12 weeks treatment， using the Unified Parkinson's Disease Rating Scale（UPDRS）， Wearing-Off Questionnaire-9（WOQ-9）， Montreal Cognitive Assessment（MoCA）， Mini-Mental State Examination（MMSE）， Depression Rating Scale（DRS）， Hamilton Depression Scale（HAMD）， Hamilton Anxiety Scale（HAMA）， PD Questionnaire-39（PDQ-39）， and Pittsburgh Sleep Quality Index（PSQI）. Repeated measures ANOVA was utilized to evaluate the effects of time， group， and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment， with decreases in UPDRS total score， WOQ-9 total score， DRS score， HAMD score， HAMA score， PDQ-39 score， and PSQI score， and increases in MoCA and MMSE scores（P＜0.05）. Compared with the control group， the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks （P＜0.05）. Repeated measures ANOVA showed significant time main effects， group main effects， and their interaction across all outcome measures（P＜0.01）. Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS， WOQ-9， DRS， HAMD， HAMA， PDQ-39， and PSQI scores， while positively correlated with MoCA and MMSE scores after 12 weeks of treatment（P＜0.05）. Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function， non-motor symptoms， cognitive function， depression and anxiety， quality of life， and sleep quality in patients with PD， with good safety.

β2-adrenergic receptor （β2-AR） agonists are widely used as first-line drugs in the treatment of bronchial asthma （hereinafter referred to as “asthma”）， but long-term use can lead to β2-AR desensitization and reduce its clinical efficacy， resulting in poor symptom control of some asthma patients. The mechanism of β2-AR desensitization induced by β2-AR agonists mainly includes slow hyposensitization （related to the decrease of β2-AR density in airway mucosa） and rapid hyposensitization （related to the mechanism of stimulatory G protein decoupling）. Cyclic adenosine monophosphate（cAMP）-protein kinase A and cAMP- exchange protein activated by cAMP signaling pathways are closely related to β2-AR desensitization. Glucocorticoids， peroxisome proliferator-activated receptor-gamma agonists， ASM-024， Chinese medicine monotherapies and formulations， when combined with β2-AR agonists， can improve the sensitivity of β2-AR， so as to better control asthma symptoms.

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Objective:To investigate the effects of different doses of dexmedetomidine (Dex) on heart rate variability (HRV) in patients with non-ST-segment elevation myocardial infarction (NSTEMI).Methods:The clinical data of 144 patients with NSTEMI from January 2017 to October 2020 in the 942 Hospital of Chinese PLA were analyzed retrospectively. Among them, 36 cases were treated with Dex 0.05 to 0.15 μg/(kg·h) (Dex1 group), 36 cases with Dex 0.20 to 0.40 μg/(kg·h) (Dex2 group), 36 cases with Dex 0.50 to 0.70 μg/(kg·h) (Dex3 group), and 36 cases without Dex (control group). The changes of HRV time domain indexes, frequency domain indexes and prognosis index before and after treatment were compared among 4 groups, the time domain indexes include normal R-R interval standard deviation (SDNN), mean value of adjacent normal R-R interval standard deviation (SDANNindex), root mean square of adjacent normal R-R interval standard deviation (SDNNindex), square root of adjacent normal R-R interval difference (rMSSD) and percentage of adjacent normal R-R interval difference>50 ms to R-R interval number (PNN50); the frequency domain indexes include total power (TP), low frequency power (LF), high frequency power (HF), ultra-low frequency power (VLF) and LF/HF; the prognostic indexes include ICU stay time, vasoactive drug use time, 28-day mortality and incidence of complication.Results:There was no significant difference in HRV indexes among 4 groups before treatment ( P>0.05); after treatment, except for LF/HF in Dex2 group and Dex3 group was significantly lower than that in control group and Dex1 group, other HRV indexes were significantly higher than those in control group and Dex1 group, and there were statistical differences ( P<0.05). There was no significant difference in 28-day mortality among 4 groups; the ICU stay time and vasoactive drug use time in Dex2 group were significantly shorter than those in control group, Dex1 group and Dex3 group: (7.14 ± 1.25) d vs. (9.08 ± 1.68), (9.53 ± 1.98) and (9.81 ± 1.95) d, (122.67 ± 29.5) h vs. (176.15 ± 23.26), (181.72 ± 23.40) and (180.42 ± 22.90) h, the incidence of complication was significantly lower than that in control group, Dex1 group and Dex3 group: 16.67% (6/36) vs. 72.22% (26/36), 47.22% (17/36) and 61.67% (22/36), and there were statistical differences ( P<0.05); there were no statistical difference in ICU stay time, vasoactive drug use time and incidence of complication among control group, Dex1 group and Dex3 group ( P>0.05). Conclusions:Dex 0.20 to 0.40 μg/(kg·h) is well tolerated, and has less adverse reactions. It can effectively increase HRV, regulate the balance of sympathetic-vagal nerve tension, stabilize cardiovascular response and improve prognosis in patients with NSTEMI.

Objective:To investigate the therapeutic effects of a small interfering RNA (siRNA) targeting hypoxia inducible factor-1α (HIF-1α) on collagen-induced arthritis (CIA) in mice and to analyze the possible mechanism at the macrophage level.Methods:DBA/1 mice were injected with bovine type Ⅱ collagen to establish the CIA model. Then, they were injected with HIF-1α-siRNA adenovirus or negative control adenovirus through tail vein once a week for four weeks. This study included four groups: control group, CIA model group, negative control group and HIF-1α-siRNA group. Mouse bone marrow-derived macrophages (BMDMs) were isolated and cultured. The relative expression of CD206 and arginine (Arg) at mRNA level in mouse BMDMs was detected by RT-PCR. The proportions of F4/80 + CD16/32 + M1 and F4/80 + CD206 + M2 macrophages in spleen and thymus were detected by flow cytometry. Pathological changes in the ankle joint of mice were observed using HE staining. Immunohistochemistry was used to detect the expression of macrophages and the subsets in mouse synovial tissues. Results:(1) Compared with the control group, the CIA model group showed decreased expression of CD206 at mRNA level in BMDMs, but increased expression of Arg at mRNA level ( P<0.01). HIF-1α-siRNA increased the expression of CD206 at mRNA level ( P<0.05) and reduced the expression of Arg at mRNA level in BMDMs of mice with CIA ( P<0.01). (2) Compared with the control group, the mice in the CIA model group had increased proportions of F4/80 + CD16/32 + M1 macrophages in splenocytes and thymocytes ( P<0.05), but decreased proportions of F4/80 + CD206 + M2 macrophages in thymocytes ( P<0.05). HIF-1α-siRNA could down-regulate the proportions of F4/80 + CD16/32 + M1 macrophages in splenocytes and thymocytes ( P<0.05), and up-regulate the proportions of F4/80 + CD206 + M2 macrophages in thymocytes of CIA mice ( P<0.01). (3) CIA mice had synovial hyperplasia and macrophages infiltration, especially M1 macrophages, in the ankle joint. HIF-1α-siRNA could alleviate the synovial hyperplasia and macrophage infiltration. Conclusions:HIF-1α-siRNA could alleviate macrophage infiltration and synovial hyperplasia in CIA mice through reducing the proportions of M1 macrophages in thymocytes, BMDMs and synovial tissues and increasing the proportion of M2 macrophages, suggesting that HIF-1α-siRNA could treat CIA mice by regulating the differentiation of M1 and M2 macrophages.

Objective:To investigate the application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients who underwent local laparoscopic resection of liver tumors located in superior part of central liver lobe at the Affiliated Hospital of Qingdao University from January to June 2020 were collected. There were 6 males and 4 females, aged from 41 to 63 years, with a median age of 54 years. Preoperative triangular model was constructed for all patients to plan approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe. Observation indicators: (1) preoperative general situations of patients; (2) surgical situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor recurrence and survival of patients up to February 2021. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed was absolute numbers. Results:(1) Preoperative general situations of patients: hepatocellular carcinoma was found in 7 cases, inthahepatic cholangiocarcinoma was found in 2 cases and ovarian cancer with liver metastasis was found in 1 case. Three cases had tumors located in S4a segment, 2 cases had tumors located in ventral subsegment of S8 segment, 2 cases had tumors located in dorsal subsegment of S8 segment, and 3 cases had tumors across the ventral segment of S4a+S8. The diameter of tumors was (3.4±1.0)cm. (2) Surgical situation: all the 10 patients underwent R 0 resection successfully, with no intraoperative blood transfusion or conversion to open surgery. The operation time of 10 patients was (149±59)minutes, the volume of intraoperative blood loss was (294±163)mL, the minimum surgical margin of specimen was (1.1±0.2)cm. The alanine aminotransferase was (324±151)U/L on the postoperative first day, the aspartic aminotransferase was (401±113)U/L on the postoperative first day, and the duration of postoperative hospital stay was (9±4)days. No bile leakage, hemorr-hage, reoperation or other complications occurred in all patients. (3) Follow-up: 10 patients were followed up for 7?13 months, with a median follow-up time of 11 months. All patients had no margin recurrence or distant metastasis. Conclusion:It is safe and feasible to construct triangular modal for planning approach of local laparoscopic resection of liver tumors located in superior part of central liver lobe.

Objective:To determine the intervention measures for the decrease of cerebral tissue oxygen saturation during anesthesia for the congenital heart disease in children.Methods:Twenty-eight children with cardiac surgery were enrolled.Anesthesia was deepened with propofol (3 mg/kg) intravenous injection.The data of cerebral tissue oxygen saturation(SctO2),mean arterial pressure (MAP),HR,bispectral index (BIS),arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2),hemoglobin (Hb) and middle cerebral artery (MCA) mean flow velocity (Vm) at different points were collected after intravenous injection ofpropofol at 3 mg/kg.The changes of SctO2 and the influential factors were analyzed.Results:SctO2 decreased by 4.99％ after deepen anesthesia,with 95％ CI 4.33％ to 5.65％ (P＞0.05).There was no significant differince in MAP,PaO2,PaCO2,and Hb between the time points after deepen anesthesia and the baseline (P＞0.05).MCA Vm decreased obviously after deepen anesthesia for 1,5,10 min (P＜0.05).The decrease in MAP,HR,PaCO2 and MCAVm is positively correlated with the decrease in SctO2.Conclusion:The decrease of MAP,HR,PaCO2,and MCAVm is the risk factor for SctO2.To avoid the decrease,it needs to maintain the stability of SctO2 and prevent neurological complications.

OBJECTIVE: To establish a method for detecting hexamethylene diamine in workplace air by high performance liquid chromatography( HPLC).METHODS: Hexamethylene diamine in the workplace air was collected by silica gel tube,and each was added with a concentration of 0.05 mol/L sodium bicarbonate solution,each with 0.60 mL of dansyl chloride solution( a mass concentration of 240.00 mg/L),and the volume was adjusted to 5.00 mL with acetonitrile,heating for 40.00 min in bath water,acetonitrile:water( 75:25,V/V) as the mobile phase,quantitated by the standard curve method,using HPLC for determinationstandard.RESULTS: The linear range of hexamethylene diamine was 0.040 0-6.000 0 mg/L,the correlation coefficient was 0.999 3,and the detection limit was 0.003 8 mg/L,and the minimum detection concentration was 0.002 5 mg/m~3( calculated by sample volume of 3.0 L); The within-run relative standard deviation( RSD) was 2.1%-3.0%,and the between-run RSD was 2.9%-3.6%.The average desorption efficiency of the method was 91.4%-94.1%.The sampling efficiency was 98.5%-99.6%.CONCLUSION: The method is simple,rapid,sensitive,accurate and suitable for the detecting hexamethylene diamine concentration in workplace air.

Objective To investigate the relationships of neuron-specific enolase (NSE) and progastrin-releasing peptide (ProGRP) with the initial chemotherapeutic effect and survival of patients with small-cell lung cancer (SCLC).Methods A total of 197 patients with SCLC diagnosed pathologically from January 2011 to September 2013 in Shanxi Provincial Cancer Hospital were selected.x 2 test and logistic regression analysis were used to analyze the factors affecting the initial chemotherapeutic response;KaplanMeier method,log-rank test and Cox regression analysis were used to analyze the factors affecting survival of patients.Results Among the 197 patients,NSE was negative in 64 cases and positive in 133 cases;ProGRP was negative in 51 cases and positive in 146 cases;41 cases with hyponatremia and 156 cases without hyponatremia.152 cases (77.2 ％) had well response to initial treatment and 45 cases (22.8 ％) had no reaction.Univariate analysis showed that stage of disease (x2 =4.456,P =0.033) and ProGRP (x2 =13.424,P ＜ 0.001) were associated with initial therapeutic response.Logistic regression analysis showed that stage of disease (OR =0.404,95 ％ CI 0.197-0.828％,P =0.013) and ProGRP (OR =4.058,95 ％ CI 1.939-8.491,P =0.000) were the independent predictors of initial therapeutic response.Kaplan-Meier survival analysis showed that sex,age,smoking,with or without hyponatremia,stage of disease,NSE,ProGRP and number of chemotherapy cycles were all associated with 2-year survival rate (x2 values were 4.319,6.811,4.264,4.687,32.631,41.045,11.379,33.466,respectively,all P ＜ 0.05).Multivariate analysis showed that stage of disease (RR =2.110,95 ％ CI 1.491-2.985,P ＜ 0.001),number of chemotherapy cycles (RR =0.398,95 ％ CI 0.283-0.588,P ＜ 0.001) and NSE (RR =1.422,95 ％ CI 1.113-1.784,P =0.002) were independent predictors of survival.However,ProGRP was not associated with survival of patients (RR =1.065,95 ％ CI 0.854-1.328,P =0.587).Conclusions ProGRP is associated with the initial chemotherapeutic response in patients with SCLC,and it has certain clinical significance in predicting the initial chemotherapeutic effect.NSE is associated with the survival prognosis of SCLC,and it is a prognostic factor of poor survival.