Objective To determine the effects of continuous θ burst stimulation of contralateral premotor areas on post-stroke spasticity gait in patients with severe hemiplegia.Methods A pro-spective trial was conducted on 186 stroke patients with severe hemiplegia admitted to our depart-ment from January 2019 to January 2024.They were randomly into control group(93 cases,con-ventional rehabilitation training)and observation group(93 cases,continuous θ burst transcranial stimulation).In 4 weeks after treatment,gait parameters,Fugl-Meyer assessment of lower ex-tremity(FMA-LE)score,Berg balance scale(BSS)score,clinic spasticity index(CSI)score,lower limb sensation,spasticity improvement,and total effective rate were compared between the two groups.Results After treatment,both the 2 groups had significantly higher hip flexion,knee flex-ion,stride length,step frequency,step speed,FMA-LE score,BSS score,CSI score,and H wave latency,and lower two-point discrimination perception and H/M ratio when compared with the levels before treatment(P＜0.01).What's more,all above indicators were obviously better in the observation group than the control group(P＜0.01).The observation group had 1(1.1％),11(11.8％),48(51.6％),31(33.3％)and 2 cases(2.2％),respectively,of spasticity improvement grades 1,1+,2,3,and 4,and the control group had 0,7(7.5％),29(31.2％),44(47.3％),and 13 cases(14.0％),respectively,with statistical differences between the two group(P＜0.01).The total effective rate was notably higher in the observation group than the control group(96.8％vs 77.4％,x2=15.500,P＜0.01).Conclusion For severe hemiplegia patients,continuous θ burst stimulation can improve muscle spasm,restore gait,and better improve lower limb sensory and motor function.

AIM: To explore the clinicopathological and immunohistochemistry(IHC)characteristics of meibomian gland carcinoma(MGC).METHODS: Patients who were pathologically diagnosed as MGC from January 1, 2015 to December 31, 2020 in our hospital were enrolled, and their clinicopathological information was retrospectively analyzed. Cancer tissues from all the cases were IHC stained. En Vision two-step method, DAB staining, as well as hematoxylin re-staining were applied in the IHC assay.RESULTS: A total of 50 patients with 21 males and 29 females(1:1.38)were enrolled in the study, ranging from 26 to 80 years old, with a median age of 60 years. The upper eyelid, which was the predilection site, accounting for 66%(33/50). Histopathologically, moderately or poorly differentiated was in the majority(35/50, 70%). The expression rates of IHC parameters of MGC patients were as follows: GATA-3(49/50, 98%), EMA(49/50, 98%), CAM5.2(42/50, 84%), AR(41/50, 82%), MSH2(50/50, 100%), MSH6(50/50, 100%), MLH1(50/50, 100%), PMS2(50/50, 100%), Ki67(positive, 50%-90%). All the patients were followed up for 12 to 72 mo, with 5 cases of recurrence and 0 deaths.CONCLUSION: Pathological diagnosis of MGC should focus on observing cancer cells' cytoplasm to find relevant clues for cortical gland differentiation. Comprehensive analysis of multiple indicators is required when using IHC to assist diagnosis. For most MGC cancer cells, positive expressions of GATA-3, EMA, AR, CAM5.2 and a high Ki67 proliferation index could be always found. In addition, screening for Muir-Torre syndrome related IHC indicators could be also performed in diagnosing MGC simultaneously.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

In various types of inspections and self-inspections, it was found that compliance and rationalization in diagnosis and charging were the more common problems in hospital, leading to refusal of medical insurance payment. In 2022, the failure mode and effect analysis was conducted in a Grade-A tertiary hospital in Jinhua to identify the high-risk points in the process of diagnosis and treatment and charging, and building six major information technology transformation scenarios and formulating specific transformation measures, to avoid or reduce the refusal of medical insurance payment in advance. Through the digital transformation of medical insurance supervision system, a whole process intelligent supervision has been implemented, including pre event review, mid event reminder and intelligent correction, and post event big data precise analysis. It promoted compliant diagnosis and treatment of medical personnel and accurate charging, which could provide reference for other medical institutions to use medical insurance funds reasonably.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

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 provide reference for establishing stan dardized construction standard system of “internet+TCM pharmacy”. METHODS ： Questionnaire through literature review ， investigation and expert consultation were compiled. A questionnaire survey was carried out among TCM staff to understand the current situation and problems of “internet + TCM pharmacy”in Chinese medical institutions. Based on the results of the questionnaire ，a frame of standardized construction standard system for “internet+TCM pharmacy ”was tried to constructed. RESULTS & CONCLUSIONS：A total of 74 questionnaires were distributed and 74 were returned ，including 1 invalid questionnaire ，with an effective rate of 98.65％. Among the 73 respondents， more than 60％ were from TCM hospitals ，or with the title of vice senior or above ，and 55（75.3％）were national TCM characteristic technology inheritance talents. The survey results showed that more than 80％ of TCM pharmacies in medical institutions were equipped with full-time reviewers ，provided decocting service ，set up decocting room ，and carried out distribution service，and could achieve the same-day or part of the same-day delivery. More than half of the respondents believed that the prescriptions of TCM decoction pieces in their medical institutions were issued in strict accordance with the relevant requirements ， the rational drug use monitoring software was used ，and the error analysis of relevant work links was carried out regularly ， prescription coping training was regularly carried out for dispensers ，and decoction knowledge and operation process training were carried out for decoction personnel. However ，the vast majority of respondents （67，accounting for 91.8％）thought that their medical institutions only used traditional methods to control and evaluate the quality of finished decoction products. The results of the evaluation of the importance of 6 links and 17 key points of operation showed that the highest concentration of opinions was the quality of decoction pieces ，and the key points of operation were special drug treatment. The results of principle component analysis and maximum variance analysis showed that current construction of “internet+TCM pharmacy ”was mainly reflected in the two dimensions as TCM decocting ，consultation and distribution servi ces. Statistical analysis indicated that there were significant differences in staff training ，awareness of laws and policies ， regular error analysis ，patient satisfaction survey ，optimization of payment and consulting services among different levels and categories institutions （P＜0.05）. It was necessary to carry out the standardization construction of “internet+TCM pharmacy”. It is suggested that the standard system for standardized construction of“Internet + TCM pharmacy ”should be established from 5 aspects：basic construction conditions ，the standardization of procurement and acceptance ，the standardization of dispensing ，the standardization of decocting and distribution service and the standardization of pharmaceutical consultation services.

Objective:To investigate the effect of melatonin (MEL) influence on lipopolysaccharide (LPS)-induced long-term anxiety-like behavior and activation of astrocytes in septic neonatal rats.Methods:Sprague-Dawley rats were randomly(random number) assigned to the control group, LPS group and LPS+MEL group. Sepsis model was intraperitoneally injected with LPS (1 mg/kg), and neonatal rats in the MEL group were administered with MEL (10 mg/kg) 30 min after LPS injection. At different time points after injection, rats in each group were divided into three subgroups: 3 d, 7 d and 28 d. The expression of GFAP and TNF-α in the corpus callosum was detected by immunofluorescence staining and Western blot. Open-field test was applied to observe anxiety-like behaviors. In vitro, cultured neonatal SD rat astrocytes were divided into the control group, LPS group, LPS+MEL group, and LPS+MEL+luzindole group. Immunofluorescence staining was used to observe the expression of GFAP and TNF-α. Expression of GFAP, TNF-α, p-NF-κBp65, NF-κBp65 protein in astrocytes were assessed by Western blot. RT-qPCR was used to investigate the mRNA expression of GDNF and BDNF. One-way ANOVA and two-way ANOVA were used for comparison of multiple groups of variables. A P<0.05 was considered statistically significant. Results:LPS reduced the duration of movement in the central area and distance in the central area/total distance in open-field test, while melatonin evidently reversed the LPS-induced anxiety-like behavior. Compared with the LPS group, the expressions of GFAP and TNF-α were significantly decreased in the corpus callosum at 3 d and 7 d in the MEL group ( P< 0.05). Compared with the LPS group, MEL could significantly decrease the expression of GFAP, TNF-α and p-NF-κBp65 in astrocytes ( P< 0.05), which could be blocked by Luzindole. In addition, compared with the LPS group, MEL pretreatment could reverse the down regulation of GDNF and BDNF induced by LPS ( P<0.05). Conclusions:MEL can relieve LPS-induced long-term anxiety-like behavior in septic neonatal rats. The mechanism may be related to the inhibition of astrocyte activation and inflammatory reaction through NF - κ B pathway.

Objective:To summarize the clinical features of intestinal Beh?et′s disease, so as to provide reference for the diagnosis of the disease.Methods:From April 1 2014 to January 31 2019, the clinical data of 47 patients diagnosed as intestinal Beh?et′s disease at the Second Hospital of Hebei Medical University were retrospectively analyzed, which included initial symptoms, gastrointestinal symptoms, complications, erythrocyte sedimentation rate (ESR), the levels of C reactive protein (CRP), hemoglobin, serum albumin, results of acupuncture test, gastrointestinal involved site and ulcer shape. At the same time, gender differences of clinical manifestations were compared. Chi-square test was used for statistical analysis.Results:Among 47 patients with intestinal Beh?et′s disease, the initial symptoms of 26 (55.3%) cases were gastrointestinal symptoms. Abdominal pain was the most common symptom, the others were diarrhea, anorexia, abdominal distension and perianal abscess, and the incidence rate was 80.9%(38/47), 46.8% (22/47), 42.6% (20/47), 36.2% (17/47) and 2.1% (1/47), respectively. The main complications were gastrointestinal bleeding, perforation and obstruction, and the incidence rates was 40.4% (19/47), 4.3% (2/47) and 4.3% (2/47), respectively. Thirty-seven (78.7%) patients had different degrees of hypoalbuminemia (serum albumin<35 g/L). The CRP level of 36(76.6%) patients increased. The ESR of 36 (76.6%) patients increased. Twenty-two (46.8%) patients had mild anemia (hemoglobin<90 g/L). The acupuncture test was positive in 25 (53.2%) patients. The involved sites of gastrointestinal tract were terminal ileum and ileocecal junction, colon, esophagus, duodenum and jejunum, stomach, and rectum, the proportion was 57.4% (27/47), 27.2% (13/47), 23.4% (11/47), 23.4% (11/47), 17.0% (8/47) and 8.5% (4/47), respectively. All 47 (100.0%) patients had oral ulcers. 62.1%(18/29) patients presented with multiple ulcers under endoscope. The shape of ulcer was round ulcer, irregular ulcer, and longitudinal ulcer, the proportion was 48.3% (14/29), 34.5% (10/29) and 17.2 (5/29), respectively. The incidence rate of genital ulcer of female patients with intestinal Beh?et′s disease was higher than that of male patients with intestinal Beh?et′s disease (85.7%, 18/21 vs. 30.8%, 8/26), and the difference was statistically significant ( χ2=14.189, P<0.01). There were no significant differences between the female group and the male group in the incidence rate of oral ulcer, abdominal pain, diarrhea, and positive rate of acupuncture test (100.0%, 21/21 vs. 100.0%, 26/26; 85.7%, 18/21 vs. 76.9%, 20/26; 42.9%, 9/21 vs. 50.0%, 13/26; 52.4%, 11/21 vs. 58.3%, 14/26, all P>0.05). Conclusions:The common clinical symptoms of intestinal Beh?et′s disease are oral ulcers, abdominal pain, diarrhea and genital ulcer. Female patients with intestinal Beh?et′s disease are more likely to develop genital ulcer than male patients with intestinal Beh?et′s disease. Multiple ulcers are more common under endoscopy, which are round ulcer, irregular ulcer and longitudinal ulcer. The most common sites are the terminal ileum and ileocecal junction, followed by colon, esophagus and other parts.

Objective:To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia (CML) in China.Methods:From the end of April to mid-May in 2020, a cross-sectional survey, by filling out a survey questionnaire, was conducted to explore the first-line choice of tyrosine kinase inhibitors (TKI) , current medications, drug switch and major molecular responses (MMR) as well as the variables associated with them in patients in China.Results:Data of 2933 respondents with CML from 31 provinces, municipalities, and autonomous regions across the country were included in this study. 1683 respondents (57.4%) were males. Median age was 38 (16-87) years old. 2481 respondents (84.6%) received imatinib as first-line TKI; 1803 (61.5%) , the original new drug (branded drug) . When completing the questionnaire, 1765 respondents (60.2%) were receiving imatinib; 1791 (61.1%) , branded drug. 1185 respondents (40.4%) had experienced TKI switch. With a median follow-up of 45 (3-227) months, 1417 of 1944 (72.9%) respondents with newly diagnosed CML in the chronic phase achieved MMR. Multivariate analysis showed that the respondents with urban household registration ( OR=0.6, 95% CI 0.5-0.8, P<0.001) , ≥ bachelor degree ( OR=0.5, 95% CI 0.4-0.7, P<0.001) , and in the advanced phase at diagnosis ( OR=0.5, 95% CI 0.3-0.8, P=0.001) less preferred Chinese generic TKI, while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region ( OR=1.7, 95% CI 1.4-2.0, P<0.001) . Moreover, the respondents in the advanced phase at diagnosis more preferred second-generation TKI ( OR=5.4, 95% CI 3.6-8.2, P<0.001) ; those ≥60 years old, less preferred second-generation TKI ( OR=0.4, 95% CI 0.2-0.7, P=0.002) . Being in the advanced phase at diagnosis ( OR=2.2, 95% CI 1.6-3.2, P<0.001) , first-line choice of imatinib ( OR=2.0, 95% CI 1.6-2.6, P<0.001) or Chinese generic drugs ( OR=1.3, 95% CI 1.1-1.6, P=0.002) , longer interval from diagnose of CML to starting TKI treatment ( OR=1.2, 95% CI 1.1-1.2, P<0.001) and longer duration of TKI therapy ( OR=1.1, 95% CI 1.0-1.1, P<0.001) were significantly associated with TKI switch; urban household registration ( OR=0.7, 95% CI 0.6-0.8, P<0.001) , ≥MMR ( OR=0.6, 95% CI 0.5-0.8, P<0.001) and unknown response ( OR=0.7, 95% CI 0.6-0.9, P=0.003) , no TKI switch. Female sex ( OR=1.4, 95% CI 1.1-1.7, P=0.003) , urban household registration ( OR=1.6, 95% CI 1.3-2.0, P<0.001) , front-line imatinib therapy ( OR=1.4, 95% CI 1.1-1.9, P=0.016) and longer duration of TKI treatment ( OR=1.2, 95% CI 1.2-1.3, P<0.001) were significantly associated with achieving a MMR or better response; age ≥ 60 years old ( OR=0.7, 95% CI 0.4-1.0, P=0.047) and TKI switch ( OR=0.6, 95% CI 0.5-0.7, P<0.001) , achieving no MMR. Conclusions:By 2020, the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it. More than half of TKIs were branded drugs. Socio-demographic characteristics and clinical variables affect their TKI choice, drug switch, and treatment response.