OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

Background and aims Adeno-associated virus (AAV) is becoming an attractive vector due to its low toxicity and minimal immunogenicity. However, liver-targeted AAV gene therapy still faces challenges, such as low delivery efficiency and safety risks associated with high vector doses. Isolated hepatic perfusion (IHP) has been explored as a localized drug delivery method, yet its full potential in gene therapy remains under investigation. Here, we investigated the efficiency of AAV8 delivery via the IHP route and its preference for hepatic transduction. Methods The IHP route was established through surgery in rats and cynomolgus monkey, and the AAV8-dTomato solution was injected into the entire liver through the inflow tract and maintained for 10 min. One week later, liver tissues were obtained, and the dTomato fluorescence expression area fraction and intensity were analyzed. Results AAV8-dTomato delivery via the IHP resulted in over 60% dTomato-positive areas in rat liver and showed higher efficiency than the portal vein (PV) and inferior vena cava (IVC) routes at equivalent doses. In rats, AAV8-dTomato expression was primarily periportal across IHP, PV, and IVC routes, while in cynomolgus monkey, IHP delivery showed a pericentral pattern. Conclusions In this study, we found that IHP is an effective strategy for AAV8 delivery. In addition, the distribution characteristics of AAV8, when delivered in cynomolgus monkey via IHP, provide candidate vector delivery schemes for gene therapy for different types of genetic liver diseases.

Objective To explore the efficacy and safety of pars plan vitrectomy(PPV)combined with internal limit-ing membrane(ILM)covering surgery in patients with large-diameter idiopathic macular holes(IMH)using optical coher-ence tomography angiography(OCTA)and microperimetry.Methods Twenty-three eyes of 23 patients with large-diame-ter IMH treated at the Eye Hospital Affiliated with Nanchang University from February 2023 to July 2023 were selected.The patients'best-corrected visual acuity(BCVA),hole closure rate,microcirculation[perfusion density at the superficial cap-illary plexus(PSCP)and vascular density at the retinal superficial capillary plexus(VSCP)]in the macular area(divided into central,inner and outer regions),macular sensitivity(MS),fixation stability,and foveal avascular zone(FAZ)area were observed before surgery and at 1 week,1 month,3 months,and 6 months after surgery.Changes in eye parameters before and after surgery were compared,and the correlation between parameters was analyzed.Results After a 6-month follow-up,all macular holes in the affected eyes were closed,with a closure rate of 100％.Compared to before surgery,the BCVA of the patients improved gradually at 1 week,1 month,3 months,and 6 months after surgery,and the differ-ences between any two time points were statistically significant(all P＜0.05).The FAZ area decreased at 1 week,1 month,3 months,and 6 months after surgery compared to before surgery,and the differences were statistically significant(all P＜0.05).The VSCP in the three regions showed a decrease at 1 week postoperatively and an increase at 6 months postoperatively compared to before surgery,and the differences were statistically significant(both P＜0.05).The PSCP in-creased at 3 months and 6 months postoperatively compared to before surgery,with statistically significant differences(both P＜0.05).The 12° MS increased at 1 month,3 months,and 6 months after surgery compared to before surgery,with statistically significant differences(all P＜0.05).The proportions of fixation points within 2° and 4° increased at 1 month,3 months,and 6 months postoperatively compared to before surgery,with statistically significant differences(all P＜0.05).The proportion of fixation points within 4° increased at 1 week postoperatively compared to before surgery,with a statistically significant difference(P＜0.05).Correlation analysis showed that preoperative MS and the proportion of fixa-tion points within 2° were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.819,-0.790,both P＜0.05),while preoperative FAZ area and minimum hole diameter were positively correlated with BCVA(logMAR)at 6 months postoperatively(r=0.596,0.853,both P＜0.05).The preoperative VSCP in the inner and outer regions were negatively correlated with BCVA(logMAR)at 6 months postoperatively(r=-0.521,-0.570,both P＜0.05).Conclu-sion The results of OCTA and microperimetry show that after treatment with PPV and ILM covering surgery,the closure rate of large-diameter IMH is good,and all indicators have improved compared to before surgery.

BACKGROUND:Distal tibial tuberosity-high tibial osteotomy is a surgical treatment for knee osteoarthritis,but there is still a lack of clinical studies on its effect on ankle joints. OBJECTIVE:To observe the effects of distal tibial tuberosity-high tibial osteotomy on ankle angle on coronal plane of the radiography of the full length of lower limb in weight loading. METHODS:Data of 40 patients(41 knees)with distal tibial tuberosity-high tibial osteotomy from March 2021 to March 2022 were retrospectively analyzed,including 31 females and 9 males,20 left knees and 21 right knees,aged 49-75 years,mean(63.44±6.57)years.The radiographic data of the full length of the lower limb in weight loading were collected before,week 2 and week 48 postoperatively.Hip-knee-ankle angle,talar tilt angle,tilt angle of the ankle,tibiocrural angle,and tibial articular surface angle were measured before and after surgery. RESULTS AND CONCLUSION:(1)Hip-knee-ankle angle improved from(-6.24±3.69)° before operation to(2.59±3.49)° week 2 postoperatively and(2.15±3.49)° week 48 postoperatively.The tilt angle of the ankle changed from(-7.90±3.11)° before operation to(-2.51±2.59)° week 2 postoperatively and(-2.46±2.42)° week 48 postoperatively,with statistically significant difference(P<0.001).(2)There was no significant difference in talar tilt angle,tibiocrural angle,and tibial articular surface angle before and week 2 postoperatively.(3)No significant difference in the angle changes was detected between week 2 and week 48 postoperatively.(4)It is indicated that distal tibial tuberosity-high tibial osteotomy can not only correct genu varus but also improve ankle angle.This result remains stable after 48 weeks of weight-bearing activities.

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.

OBJECTIVE: To explore the percutaneous hollow screw internal fixation combined with cementoplasty in the treatment of periacetabular metastasis. METHODS: A retrospective study was performed on 16 patients with periacetabular metastasis who were treated with percutaneous hollow screw internal fixation combined with cementoplasty between May 2020 and May 2021. There were 9 males and 7 females. The age ranged from 40 to 73 years, with an average of 53.6 years. The tumor involved around the acetabulum, and 6 cases were located on the left and 10 cases on the right. Operation time, frequency of fluoroscopy, bed rest time, and complications were recorded. Before operation, and at 1 weeks, 3 months after operation, the visual analogue scale (VAS) score was used to evaluate the pain degree, the short-form 36 health survey scale (SF-36) score was used to evaluate the quality of life. At 3 months after operation, the Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the functional recovery of patients. During follow-up, the loosening of internal fixator and bone cement leakage were observed by X-ray film. RESULTS: All patients were performed operation successfully. The operation time ranged from 57 to 82 minutes, with an average of 70.4 minutes. The frequency of intraoperative fluoroscopy was 16-34 times, with an average of 23.1 times. After operation, 1 case of incision hematoma and 1 case of scrotal edema occurred. All patients felt the pain relieved after operation. The patients started walking at 1-3 days after operation, with an average of 1.4 days. All patients were followed up 6-12 months (mean 9.7 months). The VAS and SF-36 scores significantly improved after operation when compared with the preoperative scores, and the scores at 3 months after operation were significant better than those at 1 week after operation ( P<0.05). At 3 months after operation, the MSTS score ranged from 9 to 27, with an average of 19.8. Among them, 3 cases were excellent (18.75%), 8 cases were good (50%), 3 cases were fair (18.75%), and 2 cases were poor (12.5%). The excellent and good rate was 68.75%. And 11 patients returned to normal walking, 3 had mild claudication, and 2 had obvious claudication. Radiological examination showed that there were 2 cases of bone cement leakage after operation, and there was no internal fixator loosening or displacement. CONCLUSION Percutaneous hollow screw internal fixation combined with cementoplasty can effectively relieve pain and improve the quality of life of patients with periacetabular metastasis.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Spinal Fractures/surgery* ; Retrospective Studies ; Bone Cements ; Quality of Life ; Treatment Outcome ; Fracture Fixation, Internal ; Bone Screws ; Cementoplasty ; Pain

Objective:To evaluate the effect of the improved team-based learning (TBL) teaching method in the undergraduate probation course of ophthalmology based on the goal of cultivating excellent doctors.Methods:The undergraduates of clinical medicine were randomly divided into experimental group and control group. The control group ( n=50) was given conventional ophthalmology probation teaching, while the experimental group ( n=50) was given ophthalmology probation teaching of improved TBL teaching method. The theoretical examination performance and skill assessment results of students in the two groups were compared, and the subjective evaluation of the students on the teaching was also compared. SPSS 23.0 was used to conduct t-test and Wilcoxon's rank sum test. Results:The theoretical examination performance of experimental group (29.68±4.52) was better than that of control group (27.84±4.33), with significant differences ( P<0.05); the skill assessment results of experimental group (32.88±5.05) were also better than those of the control group (30.88±6.99), with significant differences ( P<0.05); the subjective evaluation of teaching effect in each item of experimental group was better than that of control group ( P<0.05). Conclusion:The improved TBL teaching method can not only improve students' theoretical knowledge and experimental skills, but also improve students' self-study and teamwork ability, which will provide a feasible educational reform plan for achieving the goal of cultivating excellent doctors.

OBJECTIVE: To investigate the effect of hand-transmitted vibration on the subjective symptoms of mine drilling workers. METHODS: A total of 117 mine drilling workers exposed to hand-transmitted vibration were selected as the exposure group, and 46 workers without hand-transmitted vibration exposure were selected as control group by judgment sampling method. The Occupational Epidemiology Questionnaire of Mine Drilling Workers was used to investigate their subjective symptoms. RESULTS: The prevalence of tinnitus, hearing loss, cough and sputum in the exposure group was higher than that in the control group(P<0.05). The occurrence rate of numbness, tingling, self-reported white fingers and cold hands in the exposure group was higher than that in the control group(P<0.05). The total rate of symptoms of hand in the exposure group was higher than that in the control group(38.5% vs 21.7%, P<0.05). The multivariate logistic regression analysis results indicated that hand-transmitted vibration exposure and service length were risk factors of abnormal hand symptoms(P<0.05). CONCLUSION: Occupational hand-transmitted vibration exposure can affect the hand subjective symptoms of mine drilling workers, and the length of service is a synergistic influencing factor.

We present a case of severe COVID-19 in a male newborn. A 22-day infant was transferred to Children's Hospital Affiliated to Zhengzhou University due to "intermittent fever for 18 days". The parents of the infant had been living in Wuhan and returned to Xinyang 9 days before delivery. Suspecting COVID-19 infection, a cesarean section was performed at 38 gestational weeks. The diagnosis of COVID-19 in the mother was confirmed at 2 days postpartum, as well as the father and the grandparents-in-law within 5 days postpartum. The baby developed fever and cough 5 days after birth, and a positive result for the new coronavirus nucleic acid test in the pharyngeal swab was shown 6 days after birth. The fever continued intermittently for 18 days, whilst nasal catheter oxygen inhalation treatment was administered. The percutaneous oxygen saturation decreased to 79% after cessation of oxygen, and the baby was transferred to the hospital for further treatment. After admission, the infant presented with cough, occasional choke, shortness of breath despite nasal catheter oxygen inhalation, increased heart rate, low urine volume, and an enlarged liver 2 cm below the right costal margin. The baby was diagnosed with severe COVID-19 accompanied by anemia, hyperkalemia, pneumonia, and atrial septal defect seen on the echocardiogram. After isolation in an incubator, oxygen inhalation, cardiotonic intervention, blood transfusion and antiviral treatment, the patient made a good recovery, with good breastfeeding, significant resorption of the lung inflammation and no fever or respiratory symptoms. The baby was discharged 14 days after hospitalization, with negative results for nucleic acid test of pharyngeal swab for 2 consecutive times.

Objective:To compare the clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with expanded polytetrafluoroethylene (ePTFE)-covered stent and drug combined with gastroscopy as the secondary prevention of esophageal-gastric variceal bleeding in portal hypertension.Methods:Patients with esophageal-gastric variceal bleeding who received TIPS treatment (ePTFE covered stent) or gastroscopy for the first time as the secondary prevention for portal hypertension at Nanfang Hospital of Southern Medical University through March to July 2017 were selected. One year after the operation, liver function changes, ascites remission rates, incidence of hepatic encephalopathy, re-bleeding rate, average hospitalization frequency and expenses, survival time, as well as the TIPS patency conditions were analyzed in the two groups of patients. 2 test, Kaplan-Meier method and Mann-Whitney U test were used to analyze the data.Results:There were 74 and 66 cases in the TIPS and the drug combined gastroscopy group and the follow-up duration (14.57 ± 0.79) was 12-16 months. One year after surgery, the remission rate of ascites in the TIPS group was higher 57.1% (32/56) than that of the drug combined gastroscopy group (0), and the difference was statistically significant (χ 2 = 2 = 36.73, P < 0.01). The cumulative incidence of hepatic encephalopathy at 1, 3, 6, and 12 months after surgery in the TIPS group was 32.4% (24/74), 37.8% (28/74), 40.5% (30/74), and 40.5% (30/74), respectively. The cumulative incidence of hepatic encephalopathy in the drug combined gastroscopy group was 3.0% (2/66), 3.0% (2/66), 3.0% (2/66), and 6.1% (4/66), respectively. Kaplan-Meier analysis showed that the cumulative incidence of hepatic encephalopathy in the TIPS group was higher than that of the drug combined gastroscopy group (χ 2 = 11.29, P < 0.01). The incidence of severe hepatic encephalopathy ( grade III to IV) at 1, 3, 6, and 12 months after surgery in the TIPS group was 2.7% (2/74), 0, 0, and 0, respectively. The incidence of severe hepatic encephalopathy in drug combined gastroscopy group was 0, and there was no statistically significant difference in development of hepatic encephalopathy between the two groups ( P > 0.05). The re-bleeding rates of TIPS group and drug combined gastroscopy group were 0 and 27.3% (18/66), respectively, and the difference was statistically significant (χ 2 = 22.42, P < 0.01). There was no death reported during the follow-up period between both groups. The hospitalization frequency times (1.45 ± 0.80) in TIPS group was lower than that of the drug combined gastroscopy group times (3.24 ± 1.80), and the difference was statistically significant ( U = -4.52, P < 0.01). Conclusion:In the prevention of esophageal-gastric variceal bleeding, TIPS (ePTFE-covered stent) treatment has the advantages of reducing re-bleeding rate, high ascites remission rate and hospitalizations frequency. In addition, patients treated with TIPS have a higher incidence of hepatic encephalopathy than that of drugs combined with gastroscopy. However, TIPS did not exacerbate the incidence of hepatic encephalopathy, and there was no significant difference in the 1-year survival rate after TIPS and drugs combined with gastroscopy treatment.