OBJECTIVE To explore the mechanism by which Gongfa Static Training regulates mitophagy through the PTEN-in-duced kinase 1(PINK1)/Parkin pathway in skeletal muscle insulin resistance in type 2 diabetes mellitus(T2DM).METHODS T2DM mouse model was established using a high-fat diet combined with streptozotocin(STZ)intraperitoneal injection.Mice were ran-domly divided into a model group,a metformin group,an aerobic exercise group,and a Gongfa Static Training group.The intervention effects of Gongfa Static Training were evaluated by measuring fasting blood glucose,Homeostatic Model Assessment of Insulin Resist-ance(HOMA-IR),glycated hemoglobin(HbA1c),lipid metabolism indicators,mitochondrial function in the gastrocnemius muscle,and the expression of PINK1 and Parkin-related genes and proteins.RESULTS Gongfa Static Training significantly reduced fasting blood glucose,HbA1c,and insulin resistance index in T2DM mice,improved lipid metabolism,and enhanced insulin sensitivity.It improved the structure and function of mitochondria in the gastrocnemius muscle by upregulating the mRNA and protein expression of PINK1 and Parkin.CONCLUSION Gongfa Static Training improves mitochondrial function and insulin resistance in the skeletal muscle of T2DM mice by regulating the PINK1/Parkin pathway.

OBJECTIVE To explore the mechanism by which Gongfa Static Training regulates mitophagy through the PTEN-in-duced kinase 1(PINK1)/Parkin pathway in skeletal muscle insulin resistance in type 2 diabetes mellitus(T2DM).METHODS T2DM mouse model was established using a high-fat diet combined with streptozotocin(STZ)intraperitoneal injection.Mice were ran-domly divided into a model group,a metformin group,an aerobic exercise group,and a Gongfa Static Training group.The intervention effects of Gongfa Static Training were evaluated by measuring fasting blood glucose,Homeostatic Model Assessment of Insulin Resist-ance(HOMA-IR),glycated hemoglobin(HbA1c),lipid metabolism indicators,mitochondrial function in the gastrocnemius muscle,and the expression of PINK1 and Parkin-related genes and proteins.RESULTS Gongfa Static Training significantly reduced fasting blood glucose,HbA1c,and insulin resistance index in T2DM mice,improved lipid metabolism,and enhanced insulin sensitivity.It improved the structure and function of mitochondria in the gastrocnemius muscle by upregulating the mRNA and protein expression of PINK1 and Parkin.CONCLUSION Gongfa Static Training improves mitochondrial function and insulin resistance in the skeletal muscle of T2DM mice by regulating the PINK1/Parkin pathway.

Objective: To investigate the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods: In this retrospective study, 7 children diagnosed with Talaromyces marneffei infection in Shenzhen Children's Hospital from July 2017 to October 2021 were recruited. The clinical features, radiology, pathogen detection, immunological evaluation, treatments, and prognosis were analyzed. Results: In 7 cases, 5 were male, 2 were females. The age was from 0.75 to 8.75 years. The main clinical manifestations were fever in 7 cases, cough in 6 cases, malnutrition in 4 cases, papules in 2 cases and medical history of recurrent infection in 3 cases. Physical examination showed that all 7 patients had hepatosplenomegaly, 4 had superficial lymphadenopathy. Laboratory examination showed that 6 cases had decreased hemoglobin and 3 cases had decreased platelet. Chest CT showed that 4 cases had patchy shadows, pleural effusion, mediastinal or axillary lymph node enlargement, 3 had nodular shadows and 2 had cavities. The positive ratio of Talaromyces marneffei culture was 2/2 with tissue samples, 4/5 with bone marrow. The positive ratio was 3/4 by metagenomic next generation sequencing. The fungus was detected in 3 cases by smear microscopy of bone marrow and (or) peripheral blood. All patients were negative for human immunodeficiency virus by the immune function assay. However, 5 cases were confirmed as primary immunodeficiency disease, including 2 cases with high IgM syndrome, 2 with STAT1 gene variation, and the last with severe combined immunodeficiency (IL2RG gene variation). Exclude 1 case which gave up treatment due to acute intracranial infection, and the other patients received effective treatments along with amphotericin B, voriconazole, and itraconazole alone or in combination. Two cases relapsed after medication withdrawal, but 1 case got complete rehabilitation after hematopoietic stem cell transplantation. Conclusions: The clinical manifestations involve multisystem, the common charateristics are fever and cough. The chest CT imaging manifestations are diverse, it should be considered in differentiating tuberculosis. The amphotericin B, voriconazole and itraconazole are effective, but it will easily relapse when withdrawing those antifungal agents.
Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Child, Preschool ; Cough ; Female ; Fever ; Humans ; Infant ; Itraconazole/therapeutic use* ; Male ; Mycoses ; Retrospective Studies ; Talaromyces ; Voriconazole

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

Objective: To analyze the short-term efficacy of sleeve gastrectomy plus uncut jejunojejunostomy (SG+uncut JJB) for patients with obesity. Methods: This prospective study was conducted in the General Surgery Department of Beijing Chaoyang Hospital from January to December 2020 (NCT04534504). The inclusion criteria were patients with a body mass index (BMI) of >32.5 kg/m², type 2 diabetes mellitus (T2DM) or at least two comorbidities with a BMI of 27.5-32.5 kg/m², a waist circumference of >90 cm (male) or >85 cm (female), and those aged between 16 and 65 years. The exclusion criteria included patients who were pregnant, diagnosed with severe neurological or mental illnesses, long-term users of antidepressants and immunosuppressants, and diagnosed with severe gastroesophageal reflux disease or underwent revision surgery. Patients with incomplete follow-up data or insufficient follow-up time were also excluded. Patients were divided into SG-uncut JJB group and SG group according to doctor's recommendation and patients' wills. The primary endpoint was the percentage of excess weight loss (%EWL), and the secondary endpoints were the percentage of total weight loss (%TWL) and the T2DM remission rate. All patients were regularly followed up until the end of December 2020. Results: After excluding seven patients who did not meet the inclusion criteria, 47 eligible patients were finally identified, with 21 in the SG+uncut JJB group and 26 in the SG group. The operation time (140 [110-180] minutes vs. 90 [70-180] minutes, Z=-3.642, P=0.001) and total cost ([54,000 ± 6000] yuan vs. [49,000 ± 7000] yuan, t=2.590, P=0.013) were slightly higher in the SG+uncut JJB group than in the SG group (all P<0.05). However, no significant differences were observed in terms of postoperative hospital stay, operative blood loss, and postoperative complications between the two groups (all P>0.05). The incidence of nausea and vomiting was significantly lower in the SG+uncut JJB group than in the SG group (9.5% [2/21] vs. 46.2% [12/26], χ²=7.453, P=0.006}. The %EWL and %TWL in the SG+uncut JJB group tended to increase gradually with time. The same trend was also observed in the SG group during the first 6 months of follow-up. The 12-month %EWL and %TWL in the SG group were slightly lower compared with the 6-month %EWL and %TWL (P=0.001). The 12-month %EWL values in the SG+uncut JJB and SG groups were (72.4%±12.3%) and (63.6%±25.7%), respectively. However, no significant differences were observed between the two groups in terms of %EWL. Moreover, the 1-month ([11.1%±2.4%] vs. [8.2%±4.4%], P=0.011) and 12-month %TWL ([29.7%±6.9%] vs. [20.3%±7.2%], P=0.001) were significantly higher in the SG+uncut JJB group than in the SG group. No significant differences were observed in terms of T2DM and hypertension remission (all P>0.05). Conclusion: SG+uncut JJB might achieve a promising weight-loss effect similar to SG with a relatively lower incidence of postoperative nausea and vomiting, and it might be an effective and safe approach for obesity management.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Diabetes Mellitus, Type 2/surgery* ; Gastrectomy ; Gastric Bypass ; Immunosuppressive Agents ; Laparoscopy ; Obesity/surgery* ; Obesity, Morbid/surgery* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; Weight Loss

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ²=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ²=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.
Humans ; Neoadjuvant Therapy/methods* ; Abscess ; Retrospective Studies ; Intestinal Obstruction/etiology* ; Stents ; Colorectal Neoplasms/therapy* ; Necrosis

OBJECTIVE: To evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical (VATS). METHODS: From January to December 2020, 97 participants were randomly assigned to the TEAS group (49 cases) and the control group (48 cases) by a random number table. The patients in the TEAS group received TEAS, at the bilateral Neiguan (PC 6) and Zusanli (ST 36) acupoints. The control group received sham TEAS. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the incidence of pstoperative cognitive dysfunction (POCD), diagnosed based on the changes in the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes were plasma levels of S100β protein and neuron-specific enolase (NSE). RESULTS: The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group [day 1 after surgery: 28.3% (13/46) vs. 52.3% (23/44), P=0.028; day 3 after surgery: 21.7% (10/46) vs. 40.9% (18/44), P=0.043]. Compared with baseline, the MMSE and MoCA scores decreased to various extents in both groups. The MMSE scores on day 1, 3, and 5 after surgery and MoCA scores on day 1, 3, 5, and 7 after surgery in the TEAS group were higher than those in the control group (all P<0.05) in both groups. Compared with baseline, the plasma levels of S100β and NSE were significantly increased at 4, 8, 12, 24 h after surgery (all P<0.05). Compared with the control group, the plasma levels of S100β and NSE were lower in the TEAS group at 4, 8, 12, and 24 h after surgery (all P<0.05). No obvious adverse events were found during the trial. CONCLUSION Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.
Acupuncture Points ; Cognition ; Humans ; Postoperative Period ; Thoracic Surgery, Video-Assisted/adverse effects* ; Transcutaneous Electric Nerve Stimulation

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.

Objective:To observe the G protein-coupled receptor 48 (GPCR48) expression in hepatocellular carcinoma (HCC) cell lines with different metastatic potential and its characteristics effect on the invasion and metastasis of Huh7 hepatoma cells via epithelial-mesenchymal transition (EMT).Methods:Western blot was used to detect the protein expression level of GPCR48 in HCC cells with different metastatic potential. The lentivirus vector expressing GPCR48 gene was constructed. GPCR48 was overexpressed in Huh7 hepatoma cells. The GPCR48 overexpression level was detected by real-time PCR and Western blot. Transwell invasion and migration assay was used to detect the Huh7 hepatoma cells invasion and migration ability in the Control, Mock and GPCR48 overexpression group. Real-time PCR and Western blot were used to detect Huh7 hepatoma cells mRNA and protein expression levels of the EMT related markers (E-cadherin, N-cadherin, vimentin, and γ catenin) in the Control, Mock and GPCR48 overexpression groups, respectively. Analysis of variance was used to compare the differences between data sets.Results:GPCR48 protein expression level in metastatic HCC cell lines was significantly higher than non-metastatic HCC cell lines ( P < 0.05). The lentivirus vector expressing the GPCR48 gene had effectively transfected the Huh7 hepatoma cells and stably expressed the GPCR48mRNA and protein. Compared with the Mock and the Control group, Huh7 hepatoma cells invasion and migration ability in the GPCR48 overexpression group was significantly enhanced ( F≥5.54, P < 0.05), and the mRNA and protein expression levels of epithelial phenotypic markers E-cadherin and γ-catenin were decreased ( P < 0.05). The mRNA and protein expression levels of the mesenchymal phenotypic markers N-cadherin and Vimentin were increased ( P < 0.05), indicating that EMT changes occurred in Huh7 hepatoma cells had overexpressed GPCR48. Conclusion:GPCR48 expression level is positively correlated with the metastatic potential of HCC cells. GPCR48 overexpression can down-regulate the expression of epithelial phenotypic markers and up-regulate the expression of mesenchymal phenotypic markers, and induce EMT changes in HCC cells, thus promoting HCC cells invasion and migration.

Objective To investigate the expression of microRNA-152 in hepatocellular carcinoma, and analyze the correlation of miR-152 expression with the clinicopathological characteristics of hepatocellular carcinoma(HCC) patients. Methods Real-time PCR was used to detect the expression of miR-152 in tissue specimens from HCC and the adjacent non-cancerous hepatic tissues collected from 56 patients who underwent surgical treatment for primary HCC. The association between the expression of miR-152 and the clinical pathological characteristics and prognosis of HCC patients was analyzed. Results The relative expression of miR-152 in hepatocellular carcinoma and corresponding adjacent non-carcinoma tissues were 0.616±0.041 and 0.768±0.042 (P=0.011). The expression of miR-152 was significantly associated with TNM stages (P=0.042), tumor differentiation (P=0.035), metastasis (P=0.048) and venous invasion (P=0.042). There was no significant association between the miR-152 expression and gender, age, AFP level, tumor number or tumor grade. The OS (P=0.035) and PFS (P=0.012) in the low miR-152 expression group were obviously shorter than those in the high miR-152 expression group. Multivariate Cox regression analysis showed that the low expression of miR-152, tumor recurrence and pathological classification were significant independent prognostic factors for the prognosis of hepatocellular carcinoma patients. Conclusion The expression of miR-152 is decreased in hepatocellular carcinoma tissues, and the low expression of miR-152 is significantly associated with TNM stages, tumor differentiation, metastasis, venous invasion and the prognosis of HCC patients.