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

Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control. Methods: T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability. Conclusion The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.

Objective:To summarize the experience of diagnosis and treatment of unexplained neonatal intestinal perforation.Methods:A case summary was conducted.Intestinal perforation children who showed unclear etiology during surgical exploration in Fujian Children′s Hospital from October 2017 to October 2023 were retrospectively analyzed.The perforation characteristics, pathological characteristics, etiological analysis and surgical methods were analyzed, and the diagnosis and treatment experience was summarized.Results:There were 21 neonates with unexplained intestinal perforation, including 15 boys and 6 girls.There were more full-term infants (12 cases) than preterm ones (9 cases), and more neonates with normal birth weight (12 cases) than those with low birth weight (9 cases).Intraoperative perforation was detected in the ileum in 13 cases and colon in 8 cases.The perforation diameter ranged between 0.5-2.0 cm.Single perforation was detected in 20 cases, and 1 case had two perforations.All patients underwent full-layer multipoint biopsy and enterostomy.Pathological reports after surgery showed that Hirschsprung disease was confirmed in 10 cases, and Hirschsprung disease allied disorders were diagnosed in 8 cases.The remaining 3 cases had normal ganglion cells, and 2 cases of them had spontaneous intestinal perforation, and 1 case had meconium ileus.After operation, 3 cases gave up treatment, 1 case died, and 17 patients were discharged from hospital at the first stage.Nine cases with Hirschsprung disease received radical surgery at the age of 3-6 months.Six out of 8 patients with Hirschsprung disease allied disorders underwent fistula closure surgery after accurate evaluation.Among the 6 children who received fistula closure surgery, 1 case underwent Santulli enterostomy because of inability to defecate and abdominal distension after surgery.Two of the 6 children undergoing fistula closure surgery were still being followed up.Two cases of spontaneous intestinal perforation and 1 case of meconium ileus underwent fistula closure surgery at the age of 3 months, and postoperative defecation was normal.Conclusions:Intestinal neuronal dysplasia, meconium ileus combined with intestinal perforation and spontaneous intestinal perforation should be considered in unexplained neonatal intestinal perforation.It is recommended that enterostomy and multipoint biopsy should be performed to clarify the pathology before further treatment in children with unexplained intestinal perforation.Santulli enterostomy is a feasible staging operation.

Objective:To summarize the experience of diagnosis and treatment of unexplained neonatal intestinal perforation.Methods:A case summary was conducted.Intestinal perforation children who showed unclear etiology during surgical exploration in Fujian Children′s Hospital from October 2017 to October 2023 were retrospectively analyzed.The perforation characteristics, pathological characteristics, etiological analysis and surgical methods were analyzed, and the diagnosis and treatment experience was summarized.Results:There were 21 neonates with unexplained intestinal perforation, including 15 boys and 6 girls.There were more full-term infants (12 cases) than preterm ones (9 cases), and more neonates with normal birth weight (12 cases) than those with low birth weight (9 cases).Intraoperative perforation was detected in the ileum in 13 cases and colon in 8 cases.The perforation diameter ranged between 0.5-2.0 cm.Single perforation was detected in 20 cases, and 1 case had two perforations.All patients underwent full-layer multipoint biopsy and enterostomy.Pathological reports after surgery showed that Hirschsprung disease was confirmed in 10 cases, and Hirschsprung disease allied disorders were diagnosed in 8 cases.The remaining 3 cases had normal ganglion cells, and 2 cases of them had spontaneous intestinal perforation, and 1 case had meconium ileus.After operation, 3 cases gave up treatment, 1 case died, and 17 patients were discharged from hospital at the first stage.Nine cases with Hirschsprung disease received radical surgery at the age of 3-6 months.Six out of 8 patients with Hirschsprung disease allied disorders underwent fistula closure surgery after accurate evaluation.Among the 6 children who received fistula closure surgery, 1 case underwent Santulli enterostomy because of inability to defecate and abdominal distension after surgery.Two of the 6 children undergoing fistula closure surgery were still being followed up.Two cases of spontaneous intestinal perforation and 1 case of meconium ileus underwent fistula closure surgery at the age of 3 months, and postoperative defecation was normal.Conclusions:Intestinal neuronal dysplasia, meconium ileus combined with intestinal perforation and spontaneous intestinal perforation should be considered in unexplained neonatal intestinal perforation.It is recommended that enterostomy and multipoint biopsy should be performed to clarify the pathology before further treatment in children with unexplained intestinal perforation.Santulli enterostomy is a feasible staging operation.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the clinical effect of Beling Weitong granule combined with proton pump inhibitors in senile gastroesophageal reflux disease(GERD).Methods:A total of 186 patients with GERD treated in the Second People′s Hospital of Dujiangyan from January 2020 to December 2021 were retrospectively selected as the study subjects, of which 93 patients received proton pump inhibitor (prilosec) orally (control group) and 93 patients received Beling Weitong granule combined with prilosec orally (combination group). Both groups were treated for 8 weeks. Symptom score, reflux symptom-based questionnaire (GERDQ) score, clinical efficacy, serum levels of gastrin-17 (G-17), motilin (MTL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) before and after treatment and safety were compared between the two groups.Results:After treatment, the symptom score and GERDQ score in the combination group were lower than those in the control group: (8.28 ± 2.57) scores vs. (15.68 ± 3.69) scores, (8.15 ± 2.23) scores vs. (10.50 ± 2.45) scores, there were statistical differences ( P<0.05). The total effective rate in the combination group was higher than that in the control group: 96.77% (90/93) vs. 87.10% (81/93), there was statistical difference ( χ2 = 5.87, P<0.05). After treatment, the levels of serum G-17 and MTL in the combination group were higher than those in the control group, the levels of IL-6 and TNF-α were lower than those in the control group: (7.48 ± 0.96) pmol/L vs. (6.55 ± 0.83) pmol/L, (206.96 ± 37.83) pg/L vs. (184.75 ± 35.69) pg/L, (9.38 ± 1.92) ng/L vs. (14.13 ± 2.04) ng/L, (9.41 ± 1.85) ng/L vs. (12.01 ± 2.11) ng/L, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Beling Weitong granule combined with proton pump inhibitor in the treatment of senile gastroesophageal reflux disease is effective, and it is safe.

Objective:To compare the impact of different portal exposure techniques in the Kasai surgery on children with type Ⅲ. biliary atresia during their different perioperative periods.Methods:A retrospective study was performed on the data of children with type Ⅲ. biliary atresia who underwent Kasai surgery at Fujian Children's Hospital from January 2017 to October 2020. Of 45 children enrolled in this study, there were 24 males and 21 females, aged (71.3±21.0) days. Patients who had left and right branches of the portal vein and the left and right hepatic arteries in the portal area being completely freed and elastically stretched during the Kasai operation were included into the free group ( n=22) and the remaining patients were included in the control group ( n=23). Postoperative hospital stay, postoperative direct bilirubin levels, postoperative complications and transplant-free survival after the Kasai operation were compared between the 2 groups. Results:Postoperative hospital stay of (17.1±4.4) d in the free group was significantly lower than that in the control group (20.1±5.4) d, ( t=2.07, P=0.044). The direct bilirubin level at 3 months after surgery for the control group was 30.0 (109, 108.0)μmol/L, which was significantly higher than that of 14.5 (4.0, 37.5) μmol/L in the free group ( Z=-2.16, P=0.031). Twenty-one patients (91.3%) in the control group had frequent attacks of postoperative cholangitis, compared with 13 patients (59.1%) in the free group. The difference was statistically significant (χ 2=4.69, P=0.030). Eleven surviving patients (47.8%) in the control group did not undergo liver transplantation at one year after surgery, compared with 15 patients (68.2%) in the free group. At two years after surgery, 7 surviving patients (30.4%) in the control group did not undergo liver transplantation compared with 10 patients (45.5%) in the free group. Conclusion:For children with type Ⅲ. biliary atresia, completely freeing the left and right branches of portal vein, and left and right hepatic arteries in the liver portal area, and elastically stretching these vessels to expose the portal area of the liver during Kasai surgery increased surgical safety and reduced hospital stay.

Objective:To investigate the obstetric outcomes of intracytoplasmic sperm injection and frozen-thawed embryo transfer (ICSI-FET) between donor and autologous oocytes.Methods:A retrospective cohort study was conducted to analyze the clinical data of pregnant patients who underwent ICSI-FET in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to January 2020. Totally 73 patients with donor oocytes, and 550 patients who used autologous oocytes in the same period, and the patients were matched at 1∶3 with propensity score matching (PSM), then there were 47 patients in donor group and 131 patients in autologous group. The general conditions and obstetric outcomes were compared among donor group and autologous group. Multivariate logistic regression and linear regression were applied to analyze the factors affecting perinatal complications.Results:The bilateral antral follicle count (3.08±4.78) and basal estradiol level [(71.55±45.29) pmol/L] in donor group were significantly lower than those in autologous group [14.95±6.42, (132.84±74.89) pmol/L, all P<0.001]. The birth weight of singleton in donor group [(2 916.48±537.55) g] was lower than that in autologous group [(3 326.67±503.43) g], and there was significant difference ( P<0.001). There were no significant differences in premature birth rate [21.28% (10/47) vs. 16.03% (21/131), P=0.416] and incidence of hypertensive disorder complicating pregnancy [12.77% (6/47) vs. 7.63% (10/131), P=0.448] between donor group and autologous group, but both of them had an increasing trend in donor group. Oocyte-donated ICSI-FET reduced the birth weight of singleton (MD=-388.225, 95% CI=-625.914--150.537, P=0.002). Conclusion:The perinatal outcome of oocyte-donated ICSI-FET is relatively safe, but the birth weight of singleton is lower than that of self-oocyte ICSI-FET.

Objective:To investigate the obstetric outcomes of intracytoplasmic sperm injection and frozen-thawed embryo transfer (ICSI-FET) between donor and autologous oocytes.Methods:A retrospective cohort study was conducted to analyze the clinical data of pregnant patients who underwent ICSI-FET in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to January 2020. Totally 73 patients with donor oocytes, and 550 patients who used autologous oocytes in the same period, and the patients were matched at 1∶3 with propensity score matching (PSM), then there were 47 patients in donor group and 131 patients in autologous group. The general conditions and obstetric outcomes were compared among donor group and autologous group. Multivariate logistic regression and linear regression were applied to analyze the factors affecting perinatal complications.Results:The bilateral antral follicle count (3.08±4.78) and basal estradiol level [(71.55±45.29) pmol/L] in donor group were significantly lower than those in autologous group [14.95±6.42, (132.84±74.89) pmol/L, all P<0.001]. The birth weight of singleton in donor group [(2 916.48±537.55) g] was lower than that in autologous group [(3 326.67±503.43) g], and there was significant difference ( P<0.001). There were no significant differences in premature birth rate [21.28% (10/47) vs. 16.03% (21/131), P=0.416] and incidence of hypertensive disorder complicating pregnancy [12.77% (6/47) vs. 7.63% (10/131), P=0.448] between donor group and autologous group, but both of them had an increasing trend in donor group. Oocyte-donated ICSI-FET reduced the birth weight of singleton (MD=-388.225, 95% CI=-625.914--150.537, P=0.002). Conclusion:The perinatal outcome of oocyte-donated ICSI-FET is relatively safe, but the birth weight of singleton is lower than that of self-oocyte ICSI-FET.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.