ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

Gamma glutamyltransferase 1 (GGT1) is involved in regulating processes such as redox, cell proliferation, tumor metastasis, and drug resistance, and is abnormally expressed in various tumors such as prostate cancer and clear cell renal cell carcinoma. This article summarizes the expression and role of GGT1 in various diseases, providing new ideas for further exploration of treatment strategies for GGT1 related diseases.

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Objective:To compare the short-term efficacy between proximal femoral bionic nails (PFBN) and 3G Gamma nails in the fixation intertrochanteric femoral fractures in the elderly.Methods:A retrospective study was conducted to analyze the data of 78 elderly patients with intertrochanteric femoral fracture who had been admitted to Department of Trauma Surgery, The Hospital Affiliated to Qingdao University from October 2021 to December 2022. There were 35 males and 43 females with an age of (76.0±7.9) years. By Evans classification: 6 cases of type Ⅰ, 21 cases of type Ⅱ, 24 cases of type Ⅲ, 23 cases of type Ⅳ, and 4 cases of type Ⅴ. The patients were divided into 2 groups according to their internal fixation methods: a PFBN group of 35 patients fixed by PFBN and a Gamma group of 43 cases fixed with 3D Gamma nails. The time from injury to operation, hospital stay, operation time, intraoperative blood loss, weight-bearing time, fracture healing time, and Harris hip score, visual analogue scale (VAS) and incidence of complications at 6 months after operation were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (14.0±4.0) months. There were no significant differences between the PFBN and Gamma groups in operation time [(58.9±8.2) min versus (58.1±6.8) min], intraoperative blood loss [(138.0±24.9) mL versus(126.8±25.7) mL], hospital stay [(10.9±2.9) d versus (10.3±4.0) d],fracture healing time [(5.0±1.3) months versus (5.1±1.3) months], or good and excellent rate by the Harris hip score [82.9% (29/35) versus 76.7% (33/43)], VAS score [0(0, 1) points versus 1(0, 1) points], or incidence of complications at 6 months after operation [2.9% (1/35) versus 4.7% (2/43)] (all P>0.05). However, the complete weight-bearing time for the PFBN group was (5.3±1.2) weeks, significantly earlier than that for the Gamma group [(6.9±1.4) weeks] ( P<0.05). Conclusion:In the fixation of intertrochanteric femoral fractures in the elderly patients, both PFBN and 3D Gamma nails can achieve satisfactory short-term efficacy, but PFBN is more beneficial to the functional recovery of the hip joint because it leads to earlier complete weight-bearing time than 3D Gamma nails.