Currently, histological and molecular methods are considered for the treatment of advanced non-small cell lung cancer (NSCLC). Single-agent epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase in-hibitors (ALK-TKIs) have been used as standard first-line therapies for patients with active EGFR mutation and ALK rearrangement, re-spectively. However, to date, the single-agent EGFR-TKIs as the first-line therapy for patients with known EGFR mutations has been demonstrated to provide a prolonged progression-free survival but does not affect overall survival (OS). Physicians these days focus on improving the OS of patients with advanced NSCLC. To patients with EGFR mutation, combining and maintaining EGFR-TKIs with chemotherapy could be a promising approach. In this article, various ways of combining EGFR-TKIs with chemotherapy were explored.

Objective To apply the virtual reality in balance function training for Parkinson's Disease (PD). Methods From October, 2013 to January, 2016, 31 patients with balance disorders after PD were divided into two groups:the treatment group (n=17) received virtual reality balancing games training, while the control group (n=14) received routine balance training. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), static fall index (SFI), limits of stability (LOS), dynamic fall index (DFI) and modified Barth-el Index (MBI) before and four weeks after treatment. The frequency of falls in the next six weeks was recorded. Results The scores of BBS, TUGT, SFI, LOS, DFI and MBI improved significantly in both groups after treatment (P<0.05), and improved more in scores of BBS (t=2.095), TUGT (t=-2.091), DFI (t=-2.182), LOS scores (t=2.202) and MBI (t=3.036) in the treatment group than in the control group (P<0.05). There was positive correlation between scores of BBS and MBI (r=0.899, P<0.001). The frequency of falls was less in the treatment group than in the control group (P<0.05). Conclusion Virtual reality balance training can improve the balance function for PD.

To evaluate the clinical value of a new method of guide wire extraction and single reverse-α fixation with short nasobiliary duct for oronasal conversion and fixation, patients who underwent endoscopic nasobiliary drainage in Shanghai East Hospital, Tongji University from January to August 2022 were selected. They were randomly divided into guide wire extraction and single reverse-α fixation with short nasobiliary duct group (the observation group, n=145) and guide wire taking and reverse-α fixation group (the control group, n=71). The operation time, one-time operation success rate, adverse events, comfort and satisfaction between the two groups were compared. The operation time in the observation group was significantly shorter than that in the control group [102 ( 91, 117) s VS 136 (127, 145) s, Z=-9.639, P<0.001]. The one-time operation success rate in the observation group was significantly higher than that in the control group [88.28% (128/145) VS 67.61% (48/71), χ2=13.496], the nasopharynx stimulation score [1 (1, 2) VS 2 (1, 2), Z=-4.457] and adverse events incidence [4.14% (6/145) VS 15.49% (11/71), χ2=8.475] in the observation group were significantly lower than those in the control group ( P<0.05). During the indwelling of nasobiliary duct, the bile drainage volume (179.45±81.54 mL VS 142.89±55.69 mL, t=3.407) and nursing satisfaction score (7.72±0.99 VS 6.06±1.07, t=11.337) in the observation group were higher than those in the control group, and the comfort score (3.00±1.01 VS 4.83±0.99, t=-12.642) and incidence of adverse events [3.45% (5/145) VS 14.08% (10/71), χ2=8.344] in the observation group were lower than those in the control group ( P<0.05). The operation time of nasobiliary duct removal in the observation group was significantly shorter than that in the control group (9.00±1.14 s VS 11.93±1.36 s, t=-16.616, P<0.001). In conclusion, the guide wire extraction and single reverse-α fixation with short nasobiliary duct for nasobiliary oronasal conversion and fixation in endoscopic nasobiliary drainage has the advantages of simple operation, small irritation response and low complication incidence, which is worth of clinical promotion.

Objective:To investigate the correlation between specific expression of serum micro ribonucleic acid (miRNA) and dilated cardiomyopathy (DCM) in children.Methods:Sixteen children diagnosed with DCM in Pediatric Heart Center of Beijing Anzhen Hospital from November 2013 to March 2016 were enrolled in the DCM group.Meanwhile, 12 age- and gender-matched healthy children who underwent medical examinations at the same time in the same hospital were selected as the healthy control group.Their serum was collected and miRNA sequencing was performed.The sample size was expanded at the later stage (the DCM group included 30 cases, and the healthy control group included 16 cases). The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) verification experiment was conducted on 11 miRNAs with statistically significant sequencing results.Results:Serum miRNA sequencing showed that 172 miRNAs were up-regulated but no miRNAs were down-regulated in the DCM group, compared with the healthy control group (fold change>2, P<0.001). Top 11 significantly up-regulated miRNAs were verified by qRT-PCR, and it was found that 8 of the 11 miRNAs (let-7f, let-7g, miR142-5p, miR143-3p, miR26a, miR27a-3p, miR27b-3p, and miR126-3p) in the DCM group were significantly up-regulated (all P<0.05). In the receiver operating characteristic (ROC) curves of DCM patients, the area under the curves of serum miR142-5p, miR143-3p, miR27b-3p, and miR126-3p were 0.983, 0.992, 0.915 and 0.950, respectively, which were statistically significantly different from those of the healthy control group (all P<0.05). Conclusions:Four serum miRNAs (miR-142-5p, miR-126-3p, miR-143-3p and miR-27b-3p) can distinguish children with DCM from healthy children.Circulating miRNAs are effective in screening DCM children.

Objective:To retrieve the relevant guidelines and expert consensus on self-management of patients with high-risk foot diabetes, and analyze the content of high-quality guidelines and expert consensus recommendations, so as to provide a reference for the construction of a guidance program for self-management of patients with high-risk foot diabetes.Methods:Computer-retrieved clinical practice guidelines and expert consensus for self-management of patients with high-risk foot for diabetes from databases, guideline networks, and related professional websites. The search period was from January 1, 2012 to June 5, 2022. The quality of the included literature was evaluated and the evidence was extracted and integrated by 2 researchers. Experts were invited to evaluate the summarized evidence.Results:According to the quality of literature, a total of 12 guidelines (10 at level A and 2 at level B) and 3 expert consensus (expert discussion and decision) were included, and 8 themes were defined as regular follow-up, self-assessment, foot and decompression management, exercise management, nutrition management, indicator management, psychological management, and health education, a total of 28 recommendations. Among them, there were 23 A-level recommendations and 5 B-level recommendations.Conclusions:The quality of the guidelines and expert consensus included in this study is high,the recommended level of the summarized evidence is high. This study provides the reference and basis for the clinical staff to construct and guide the clinical practice of self-management of high-risk diabetic foot patients.

Objective:To investigate the relationship between the dose of preoperative neoadjuvant radiotherapy and the pathologic complete response (pCR) rate in patients with locally advanced squamous cell esophageal cancer (ESCC).Methods:Clinical data of 116 patients with ESCC who received neoadjuvant chemoradiotherapy followed by esophagectomy in our cancer center from July 2017 to December 2019 were retrospectively analyzed. The radiation doses were divided into 2 ranges based on Grays (Gy) received: 40-45 Gy and 45 Gy or more.Results:The overall pCR rate was 38. 8%(45/116). pCR was observed in 35 out of 80(44%) patients treated with 40-45 Gy and 10 of 36(28%) patients treated with 45 Gy or more. The pCR rate did not significantly differ between two groups [(40-45 Gy) vs.( ≥ 45 Gy), P=0.105)]. Conclusions:Preoperative neoadjuvant radiotherapy with a higher dose (≥ 45 Gy) fails to increase the pCR rate in patients with locally advanced ESCC. Prospective randomized trials are required to determine the optimal dose of preoperative adjuvant radiotherapy.

Alzheimer's disease （AD） is a deleterious neurodegenerative disorder， which has become a significant public health concern and economic burden. The pathogenesis of AD is complex and involves several hypotheses such as amyloid β-protein （Aβ） deposition， Tau protein hyperphosphorylation， oxidative stress， and inflammation. There is an urgent need for a holism-based comprehensive intervention with multi-pathway， multi-level， and multi-target characteristics， which demonstrates the unique advantage of traditional Chinese medicine （TCM）. Therefore， it is of great significance to conduct and promote research on TCM treatment of AD. Danggui Shaoyaosan （DSS） from the Synopsis of Golden Chamber （《金匮要略》） by ZHANG Zhongjing （150 AD-219 AD） was originally designed for reliving gynecological ailments. It is a classic TCM formula that modulates liver and spleen and dispels blood stasis and water retention. Since the late 1980s when Japanese researchers reported its therapeutic effect on AD， it has been widely used in the clinic with clear effects. The elucidation of the mechanism of this formula helps exert its effects. Hereby， this paper reviewed relative research progress and made an analysis in terms of attenuating aberrant accumulation of Aβ and hyperphosphorylated Tau protein， anti-inflammatory and antioxidant activities， mediating neurotransmitters， ameliorating lipid metabolism， modulating gut microbiota， reduced neuron apoptosis， decreasing intracellular Ca²⁺ overloading， and increasing the expression of estradiol. This paper is expected to provide references for understanding the scientific connotation of DDS in the treatment of AD and lay a solid foundation for further investigation.

ObjectiveTo investigate the mechanism of Danggui Shaoyaosan （DSS） in the improvement of the cognitive ability of SAMP8 mice with Alzheimer's disease （AD） via regulating the ubiquitin-proteasome pathway （UPP）. MethodFifteen SAMR1 mice were used as a normal group， and 60 SAMP8 mice were randomly divided into a model group and DSS high， medium， and low-dose groups （57.6， 28.8， and 14.4 g·kg^-1·d^-1）， with 15 mice in each group. Intragastric administration was conducted for eight continuous weeks. Place navigation and spatial capacity were evaluated by Morris water maze. Pathological structure changes in neurons in the hippocampal CA1 area was detected by hematoxylin-eosin （HE） staining. The protein expression levels of hippocampal β-amyloid protein（Aβ） and phosphorylation（p）-Tau were determined by immunohistochemical staining （IHC） and enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of hippocampal ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase-1 （UCHL1）， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the escape latency was prolonged in the model group （P<0.05） with the reduced number of crossing platform quadrants and time ratio in the platform quadrant （P<0.05）. The model group decreased neurons and condensed cell bodies in the CA1 area， and increased β-amyloid precursor protein （β-APP） and p-Tau positive cells （P<0.05）. In the model group， the protein expression levels of Aβ and p-Tau were increased （P<0.05）， the mRNA and protein expression levels of Ub were increased （P<0.05）， and the mRNA and protein expression levels of E3， 26S proteasome， UCHL1， and UCHL3 were decreased （P<0.05）. As compared with the model group， the escape latency was shortened in the DSS high and medium-dose groups （P<0.05） with an increased number of crossing platform quadrants and residence time ratio （P<0.05）. The pathological changes in CA1 of each DSS group were significantly improved， and the number of β-APP positive staining cells decreased （P<0.05）. The number of p-Tau positive staining cells decreased in the DDS medium and low-dose groups （P<0.05）. The protein expression levels of Aβ and p-Tau in each DDS group decreased （P<0.05）， and the mRNA expression level of Ub in each group decreased （P <0.05）. The mRNA expression levels of 26S， E3， and UCHL3 in the DDS high and medium-dose groups increased （P<0.05）， and the mRNA expression level of UCHL1 in the DDS medium-dose group increased （P<0.05）. The protein expression level of Ub in each DDS group decreased， and the protein expression levels of 26S， E3， UCHL1+3 in the DDS high and medium-dose groups increased （P<0.05）. ConclusionDSS can improve the cognitive ability of SAMP8 mice， and its mechanism may be related to the reduction of the abnormal deposition of Aβ and p-Tau via decreasing the expression of Ub and increasing that of E3， 26S， UCHL1， and UCHL3 in the UPP.

ObjectiveTo investigate the protective effect of Danggui Shaoyaosan （DSS）-contained serum on β-amyloid （Aβ）_1-40-injured rat adrenal pheochromocytoma PC12 cells and its mechanism in regulating ubiquitin-proteasome pathway （UPP）. MethodAβ_1-40 was used to intervene PC12 cells to prepare the cell models of Alzheimer's disease （AD）， and the experiment was divided into the blank， model， and DSS-contained serum high， medium， and low-dose groups （10%， 5%， and 2.5%）. Cell viability and apoptosis were detected using cell counting kit-8 （CCK-8） method and flow cytometry， respectively. The content of Aβ and p-Tau protein was determined by enzyme-linked immunosorbent assay （ELISA）. The ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase1 （UCHL1）， and UCHL3 protein expressions of UPP were displayed using immunofluorescence cytochemistry （ICC）， and the mRNA and protein expression levels of Ub， E3-parkin， 26S， UCHL1， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultThe data of the CCK8 experiment verified that 5 μmol·L^-1 and 48 hours were the optimal conditions for modeling Aβ_1-40-injured PC12 cells. As compared with the blank group， the cell viability rate in the model group decreased （P<0.05） with an increased apoptosis rate （P<0.05）， the content of Aβ and p-Tau contents was elevated （P<0.05）， the mRNA and protein expression levels of Ub increased， and the mRNA and protein expression levels of 26S， E3， and UCHL1+3 decreased （P<0.05）. As compared with the model group， the cell viability rate in the DSS-contained medium-dose group increased （P<0.05）， whereas the apoptosis rate in each DSS-contained group decreased （P<0.05）. The content of Aβ in each DDS-contained group decreased （P<0.05）， and the content of p-Tau in the DDS-contained high and medium-dose groups decreased （P<0.05）. The mRNA expression level of Ub decreased， and that of 26S increased in each DDS-contained group （P<0.05）. The mRNA expression level of UCHL1 in the DDS-contained medium-dose group increased （P<0.05）， and the mRNA expression levels of E3 and UCHL 3 in the DDS-contained high and medium-dose groups increased （P<0.05）. The protein expression level of Ub in each DDS-contained group decreased， and the protein expression levels of 26S， E3， and UCHL1+3 in the DDS high and medium-dose groups increased. The DSS-contained serum medium-dose group exerted the optimal effect. ConclusionDSS-contained serum can increase cell viability rate， reduce cell apoptosis rate， eliminate Aβ and p-Tau protein deposits， and exert protective effects on Aβ_1-40-injured PC12 cells. Its mechanism may involve UPP via decreasing the expression of Ub and increasing that of 26S， E3， UCHL1， and UCHL3.