Objective To compare the efficacy of mediastinoscope-assisted transhiatal esophagectomy (MATHE) and functional minimally invasive esophagectomy (FMIE) for esophageal cancer. Methods Patients who underwent minimally invasive esophagectomy at Jining No.1 Hospital from March 2018 to September 2022 were retrospectively included. The patients were divided into a MATHE group and a FMIE group according to the procedures. The patients were matched via propensity score matching (PSM) with a ratio of 1 : 1 and a caliper value of 0.2. The clinical data of the patients were compared after the matching. Results A total of 73 patients were include in the study, including 54 males and 19 females, with an average age of (65.12±7.87) years. There were 37 patients in the MATHE group and 36 patients in the FMIE group. Thirty pairs were successfully matched. Compared with the FMIE group, MATHE group had shorter operation time (P=0.022), lower postoperative 24 h pain score (P=0.031), and less drainage on postoperative 1-3 days (P<0.001). FMIE group had more lymph node dissection (P<0.001), lower incidence of postoperative hoarseness (P=0.038), lower white blood cell and neutrophil counts on postoperative 1 day (P<0.001). There was no statistically significant difference in the bleeding volume, R0 resection, hospital mortality, postoperative hospital stay, anastomotic leak, chylothorax, or pulmonary infection between the two groups (P>0.05). Conclusion Compared with the FMIE, MATHE has shorter operation time, less postoperative pain and drainage, but removes less lymph nodes, which is deficient in oncology. For some special patients such as those with early cancer or extensive pleural adhesions, MATHE may be a suitable surgical method.

Objective:To investigate the modulatory function of interleukin-7 (IL-7)/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis (MG). Methods:Fifty-seven treatment-naive MG patients who were hospitalized in Department of Neurology, Nanyang Central Hospital between 2017 and 2020 as well as 35 healthy controls were enrolled. Peripheral blood was collected, while plasma and peripheral blood mononuclear cells were isolated. Plasma IL-7 and soluble CD 127 (sCD 127) were measured by enzyme linked immunosorbent assay (ELISA). Membrane-bound CD 127 (mCD 127) percentage in CD 8+T cells was measured by flow cytometry. The differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type and their correlation with Quantitative Myasthenia Gravis (QMG) score were analyzed. Purified CD 8+T cells from MG patients were stimulated with recombinant human IL-7 (5 μg/L). Changes of sCD 127 and mCD 127 level were analyzed. Levels of perforin, granzyme B, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the cultured supernatants were measured by ELISA. Immune checkpoint molecules mRNA in CD 8+T cells was semi-quantified by real-time fluorescence quantitative polymerase chain reaction. Results:Plasma IL-7 level was up-regulated in MG patients compared with controls [(293.4±74.7) pg/ml vs (233.8±70.8) pg/ml, t=3.78, P<0.001], while sCD 127 level was down-regulated in MG patients compared with controls [(102.7±13.7) pg/ml vs (131.2±20.9) pg/ml, t=7.91, P<0.001]. Peripheral CD 8+T cells percentage was up-regulated in MG patients compared with controls (35.4%±7.1% vs 30.2%±7.5%, t=3.31, P=0.001), and mCD 127+CD 8+T cell percentage was also elevated (45.5%±7.7% vs 34.7%±11.5%, t=5.44, P<0.001). There were no significant differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type. There was no significant correlation between above indices and QMG score. There were no significant differences of sCD 127 in cultured supernatants, mCD 127+CD 8+T cell percentage, or immune checkpoint molecules mRNA expression between CD 8+T cells from MG patients with and without IL-7 stimulation. IL-7 stimulation promoted the secretion of perforin [(208.1±67.2) pg/ml vs (168.8±46.2) pg/ml, t=2.16, P=0.038], granzyme B [(941.8±273.9) pg/ml vs (782.4±137.2) pg/ml, t=2.33, P=0.025], and IFN-γ [(19.1±5.2) pg/ml vs (15.3±4.5) pg/ml, t=2.47, P=0.018] by CD 8+T cells. However, there was no remarkable difference of TNF-α production between CD 8+T cells with and without IL-7 stimulation. Conclusion:Elevated IL-7-mediated signaling pathway enhanced the secretion of cytotoxic molecules and cytokines by CD 8+T cells, leading to increased activity of CD 8+T cells in MG patients.

Objective:This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) .Methods:The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed.Results:A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM ( P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI ( RR=1.827, 95% CI 1.015-3.288, P=0.044) . Conclusion:In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

Objective: To evaluate the safety and therapeutic efficacy of clinical pathways(CP)for cerebral infarction in patients aged 75 years and above. Methods: A cohort of 363 cerebral infarction patients aged 75 years and above after excluding clinical variants were recruited from January 2016 to June 2018 at the neurology department of Nanyang City Center Hospital.Patients were randomly divided into the CP group(n=184)and the control group(n=179). The day-90 modified Rankin scale score(mRS), mortality, incidences of complications, length of hospital stay, total hospital costs and drug costs were compared between the two groups. Results: The proportion of patients with mRS 0-1 was higher in the CP group than in the control group(77.2% or 142/184 vs.55.3% or 99/179, χ²=19.443, P=0.000). The incidences of pulmonary infection(23.9%, 44/184)and deep venous thrombosis(14.7%, 27/184)were lower in the CP group than in the control group(42.5%, 76/179 & 29.1%, 52/179; χ²=14.101, 11.014, P=0.000, 0.001). There was a significant difference in mortality between the two groups[4.9%(9/184)vs.11.2%(20/179), χ²=4.871, P=0.027]. There was no significant difference in the other incidences of complications between the groups(P>0.05). Hospital stay length(18.3±2.9) d, total cost(2.72±0.42)×10⁴ yuan, and drug cost(0.87±0.29)×10⁴ yuan in the clinical pathway group were lower than those in the control group[(22.8±4.4)d, (3.55±0.81)×10⁴ yuan, (1.42±0.29)×10⁴ yuan](t=11.546, 12.168 and 18.335, all P=0.000). Conclusions The adoption of clinical pathways can improve medical quality, shorten hospitalization days and reduce hospitalization costs and medical costs in elderly patients with cerebral infarction.

G protein-coupled receptors(GPCRs)represent the largest class of cell surface receptors,mediating wide range of cellular and physiological processes through their transducers,G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy(cryo-EM),leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution threedimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously,which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors,and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction,providing important information for understanding GPCR signaling and the structure-based drug design.
Cryoelectron Microscopy ; Protein Binding ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled ; chemistry

Objective     To investigate the combined effects of digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training for dysphagia in patients who underwent aortic arch surgery. Methods     Forty-two consecutive patients with dysphagia after aortic arch surgery between October 2014 and November 2017 were divided into two groups including an observation group and a control group. There were 21 patients in each group. There were 17 males and 4 females at age of 51.0±6.5 years in the observation group, while 18 males and 3 females at age of 49.8±7.3 years in the control group. The patients in the observation group underwent electroacupuncture therapy and voice training (20 min per day for each therapy, 2 weeks), while the patients in the control group only received safe swallowing education and rehabilitation guidance (2 weeks). The test results, such as fibrolaryngoscope and functional oral intake scale (FOIS) score, and the data of computer phonatory detection, before and after the intervention were  compared. Results     The fibrolaryngoscope of vocal cords significantly decreased and the FOIS score significantly increased after digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training in the observation group(6.30 vs. 4.60, P<0.05). Bucking was obviously reduced. The indicators of hoarse degree, such as median pitch, fundamental frequency, jitter (0.60%±0.96% vs. 1.99%±1.86%, P=0.033), shimmer (2.47%±4.26% vs. 5.89%±3.66%, P=0.043), maximum phonation time (15.31±9.10 s vs. 3.72±8.83 s, P=0.006), maximum and loud phonation time (9.30±5.73 s vs. 2.32±2.99 s, P=0.039), mean noise-to-harmonics ratio (23.99±10.17 vs .9.98±9.37, P=0.006) and mean harmonics-to-noise ratio (0.03±0.02 vs. 0.17±0.23, P=0.019) improved after the treatment in both groups. But the improvement in the observation group was significantly better than that in the control group. Conclusion     The combination of digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training on dysphagia in patients who underwent aortic arch surgery can significantly improve the swallowing function of patients. Meanwhile, it also helps the recovery of phonic function and improves the ability of feeding and communication in these patients.

Objective To observe and compare the curative effects of zoledronic acid (ZA) combined with radiotherapy and ZA combined with chemotherapy in the treatment of bone metastasis of non-small cell lung cancer (NSCLC). Methods Seventy-eight patients with NSCLC bone metastasis treated by radiotherapy or chemotherapy were taken in our hospital from January 2010 to June 2014, including 39 cases of ZA combined conventional fractionation radiotherapy (radiotherapy combined group), and 39 cases of ZA combined with chemotherapy (paclitaxel liposome + cisplatin) (chemotherapy combined group). Each group had 39 cases. WHO objective evaluation standard, efficacy evalulation of solid tumor metastasis and curative effect standard grading of pain, anticancer agent toxicity classification standard, Karnofsky standard were used for evaluating and analyzing the patients with primary lung tumor, bone metastasis, degree of pain, adverse reactions and functional status (once before and after the treatment). Results The efficiency rate of primary lung tumor, the efficiency rate of bone metastasis, the total effective rate of pain relief and the improvement rate of functional status (Karnofsky score increased by 10 points or more)in the radiotherapy combined group and chemotherapy combined group were 82.05 % (32/39) vs. 79.49 % (31/39), 48.72 % (19/39) vs. 51.28 %(20/39), 82.05 % (32/39) vs. 84.62 % (33/39), 66.67 % (26/39) vs. 71.79 % (28/39) respectively, and the differences were not statistically significant (the values of x2 were 0.224, 0.237, 0.195, 0.259 respectively, all P> 0.05); Although the two groups showed low-grade fever, bone marrow suppression, esophagitis, liver and kidney damage, gastrointestinal reactions and other adverse reactions, the adverse reactions of two groups were close to [28.21 % (11/39) vs. 30.77 % (12/39)] (x2 = 0.314, P> 0.05). Fortunately, these reactions were controlled well after symptomatic treatment. Conclusion ZA combined with radiotherapy or chemotherapy is a safe and effective way for bone metastasis of NSCLC, which should be taken based on the individual condition of the patients.

Objective To investigate the influence of combined thrombolysis therapy on clinical effects for short -and long -term of patients with acute cerebral infarction caused by sudden occlusion of anterior and posterior circulation.Methods 75 patients with cerebral infarction caused by sudden occlusion of anterior and posterior circulation were chosen and divided into A group (46 patients)with sudden occlusion of anterior circulation and B group (29 patients)with sudden occlusion of posterior circulation by comprehensive therapy for intra -arterial thrombolysis combined with mechanical crushing and dilation.The recanalization rate,the excellent and good rate of ADL -Barthel score,NIHSS score and GCS score before and after treatment,intracranial hemorrhage rate and mortality rate of two groups were compared.Results The recanalization rates of A group and B group were 50.00%(23 /46), 89.66%(26 /29).After treatment,the excellent and good rates of ADL -Barthel score of A group and B group were 58.70%(27 /46),62.07%(18 /29).The recanalization rate of B group was significantly higher than A group(χ2 =7.44,P <0.05).There was no significant difference in the excellent and good rate of ADL -Barthel score after treatment between the two groups(χ2 =1.21,P >0.05).After treatment,the NIHSS scores of A group and B group were (8.66 ±2.48)points,(8.72 ±2.51 )points,the GCS scores of A group and B group were (12.89 ± 3.61)points,(13.10 ±3.72)points.There were no significant differences in NIHSS score and GCS score after treatment between the two groups(t =1.47,1.52,all P >0.05).After treatment,the intracranial hemorrhage rate of B group was significantly lower than A group (χ2 =8.16,P <0.05 ).There was no significant difference in the mortality rate between the two groups(χ2 =0.98,P >0.05).Conclusion Compared with acute cerebral infarction caused by sudden occlusion of anterior circulation,combined thrombolysis therapy in treatment of patients with sudden occlusion of posterior circulation has advantages including higher recanalization rate and lower risk of intracranial hemorrhage.

OBJECTIVE: To classify the external auditory canal cholesteatoma(EACC) by high-resolution temporal bone CT scans and the clinical findings of the patients, and to discuss the clinical and imaging characteristics and the surgical management of the extensive EACC. METHOD: A retrospective study was carried out among 56 patients (58 ears) with EACC and their clinical data were carefully analyzed. We classified EACC as the extensive type and the localized type. The operation strategy depended on the extent of lesion. All cases were followed up for 1 to 6 years after surgery. RESULT: There were 31 patients with localized EACC, 2 with no bone erosion and 29 (31 ears) with bone erosion within external auditory canal, and 25 patients with extensive EACC, 16 with bone erosion of intra temporal bone and 9 with bone erosion of extra temporal bone. Among all the 25 patients with the extensive type, the most common symptoms were otorrhea, otalgia and hearing loss, with 25, 23, 22 cases, respectively. The tympanic membrane (TM) was intact in 23 patients and perforated in two. The mastoid air cells in 23 patients were involved by the lesion, as well as tympanic antrum in eight, tympanic cavity in two, sigmoid sinus bony wall in five, mastoid segment of facial canal in four, and temporomandibular joint in two patients. Twenty patients underwent modified radical mastoidectomy, only one underwent reconstruction of ossicular chain, and four underwent canaloplasty. The average time of ear dry after surgery was 29 days. The postoperative hearing was improved by an average of 15 dB. No recurrence except for one patient was found during the follow-up period. CONCLUSION It was of important clinical significance to classify EACC as the extensive type and the localized type. The extensive EACC was misdiagnosed easily because of the complicated clinical manifestations. The classification was helpful for the diagnosis and the selection of surgery strategy of EACC.
Adolescent ; Adult ; Aged ; Child ; Cholesteatoma ; classification ; diagnosis ; surgery ; Ear Canal ; Female ; Humans ; Male ; Middle Aged ; Otologic Surgical Procedures ; Retrospective Studies ; Young Adult

Objective To study Tephroseris Kirilowii Turez.Houlub extract on cell cycle and apoptosis marker AnnexinV/PI of U266 in vitro..Methods U266 cells were cultured together with Tephroseris Kirilowii Turez.Houlub extract.Cell cycle and apoptosis marker AnnexinV/PI were detected by flow cytometry(FCM).Results After exposure of U266 cells to Tephroseris Kirilowii Turez.Houlub extract.the cell cycle distribution was changed.There Was a decrease of cells in the G0/G1 phase with an increase of cells in the S phase and G2/M phase and apoptosis.FCM with staining of Annexix V FITC/PI showed a dependence of apoptotic cells with the dosage of Tephroseris Kirilowii Turez.Houlub extract.Conclusion Tephroseris Kirilowii Turez extract has strong cell apoptosis effect on U266 cells.