[Summary]Diabetic peripheral neuropathy(DPN)is one of the most common complications of diabetes.The blood nerve barrier(BNB)is a barrier structure located in peripheral nerve tissue,protecting nerve tissue from toxic substances in the blood and maintaining material exchange and information transmission between nerves and blood.Studies have shown that changes in BNB may be the initial event leading to the occurrence of DPN.After BNB is destroyed,blood-borne pathogens can directly damage peripheral nerves and cause DPN.This article will review the physiological and pathological characteristics of BNB,the relationship between BNB and DPN,and the research progress in targeting BNB for the treatment of DPN.

[Summary]Diabetic peripheral neuropathy(DPN)is one of the most common complications of diabetes.The blood nerve barrier(BNB)is a barrier structure located in peripheral nerve tissue,protecting nerve tissue from toxic substances in the blood and maintaining material exchange and information transmission between nerves and blood.Studies have shown that changes in BNB may be the initial event leading to the occurrence of DPN.After BNB is destroyed,blood-borne pathogens can directly damage peripheral nerves and cause DPN.This article will review the physiological and pathological characteristics of BNB,the relationship between BNB and DPN,and the research progress in targeting BNB for the treatment of DPN.

Objective The objective of this study was to provide methodological references for the inheritance of the experience of well-known Chinese medicine doctors in the treatment of kidney disease.Methods The study collected medical case data for IgA nephropathy,diagnosed and treated by Professor Yang Nizhi's outpatient department at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2010 to 2020.The data was standardized and divided into three groups:urine and blood,urine turbidity,and renal failure groups.The study utilized the FangNet platform to apply the PageRank algorithm and calculate the THScore of different subgroups of core herbs for IgA nephropathy.The distribution pattern of syndrome differentiation and corresponding herb use regulations were visualized through Python(SciPy package,Clusterheatmap package),and the study explored and verified the drug prescription through exploratory and confirmatory factor analysis based on Pearson correlation coefficient.The weighted least squares estimation mean and variance adjusted(WLSMV)and the oblique rotated GEOMIN method were used with the Mplus software.Results The study included a total of 548 treatments for 145 patients with IgA nephropathy,with heamturia group(54 cases),urine turbidity group(51 cases),and renal failure group(40 cases).Results showed 9 basic syndromes such as Qi deficiency syndrome(91.79%),blood stasis syndrome(77.01%),damp-heat syndrome(66.06%),and Yin deficiency syndrome(38.69%).There are 24 core drugs in total,23 in the urine and blood group,21 in the urine turbidity group,and 16 in the renal failure group.These drugs mainly include qi-tonifying and yang-invigorating drugs,nourishing yin and blood drugs,promoting blood circulation and removing blood stasis drugs,and clearing heat and cooling blood drugs.The regulations for the differentiation and medication of IgA nephropathy(Z-Score>0.5 and P<0.05)were as follows:Huangqi,Shan Zhu Yu,and Tusizi were commonly used in Qi deficiency syndrome;Danshen,Ze Lan,and Shan Zhu Yu were commonly used in blood stasis syndrome;Pu Gong Ying,Shi Wei,Tao Ren,and Tu Fu Ling were commonly used in damp-heat syndrome;and Mo Han Lian,Tai Zi Shen,and Nv Zhen Zi were commonly used in Yin deficiency syndrome.Through exploratory and confirmatory factor analysis,the core drug combination factors for the treatment of IgA nephropathy by Professor Yang Nizhi were obtained as follows:F1(Tusizi,Shan Zhu Yu,Huangqi);F2(White Mao Gen,Xiao Ji,Qian Cao);F3(Nv Zhen Zi,Mo Han Lian,Tai Zi Shen);and F4(Ze Lan,Tao Ren).Conclusion This study analyzed the diagnosis and treatment experience of Professor Yang Nizhi in the treatment of IgA nephropathy by grouping,defining the core syndrome of"Qi deficiency and blood stasis,damp-heat and Yin deficiency",and the core treatment methods of"tonifying Qi,promoting blood circulation,clearing heat,and nourishing Yin"using the PageRank algorithm and Mplus factor analysis.The study provided methodological references for the inheritance of the experience of famous Chinese medicine doctors and promoted the development and utilization of traditional Chinese medicine.

Objective:To investigate the diagnostic value of urine pH, serum uric acid and related clinical indicators in the diagnosis of urinary infection stones, and to construct a prediction nomogram.Methods:The clinical data of 432 patients with urinary calculi admitted to Xuzhou Central Hospital from August 2018 to November 2023 were retrospectively analyzed. The study included 289 males and 143 females, with an average age of (52.72±13.46) years old. Among the patients, there were 98 cases of hypertension, 67 cases of diabetes, and 100 cases of recurrent calculi. Kidney stones were present in 152 cases, ureteral stones in 242 cases, and bladder stones in 38 cases. Urine bacterial culture yielded positive results in 97 cases. According to the results of postoperative stone composition analysis, the two groups were categorized as infection and no-infection stone groups, and the differences in general data between the two groups were compared. Univariate and multivariate logistic regression analysis were conducted to assess the diagnostic value of urine pH, serum uric acid, and related clinical indicators for urinary infection stones. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the clinical significance of urine pH, serum uric acid, and combined indexes in preoperatively diagnosing urinary infection stones, as well as constructing a nomogram prediction model.Results:There were 127 cases of infection stones and 305 cases of no-infection stones. The infection stone group exhibited a higher urine pH value [7.0(6.5, 7.5) vs. 6.0(5.5, 6.5), P<0.001], lower serum uric acid levels [(301.38±70.12) vs. (358.88±88.99) μmol/L, P<0.001], a higher proportion of females [55.1%(70/127) vs. 23.9%(73/305), P<0.001], younger age [(48.36±14.83)vs. (53.12±12.61)years old, P<0.001], a higher proportion of recurrence stones [34.6 %(44/127) vs. 18.4%(56/305), P<0.001], and a higher rate of positive urine bacteria culture[29.9%(38/127)vs. 19.3%(59/305), P=0.016]and nitrite test results [18.9%(24/127)vs. 6.3%(19/305), P <0.001]. Univariate logistic regression analysis revealed that urine pH value, serum uric acid levels, gender, age, recurrent stones, urine bacterial culture, and urine nitrite were associated with urinary infection stones ( P< 0.05). Multivariate logistic regression analysis revealed that urine pH value ( OR= 4.836, 95% CI 3.342-6.997), female gender( OR=2.320, 95% CI 1.286-4.186), recurrent stones ( OR=2.225, 95% CI 1.208-4.101), positive urine bacterial culture ( OR=2.061, 95% CI 1.094-3.883), serum uric acid ( OR=0.992, 95% CI 0.949-0.989), age ( OR=0.969, 95% CI 0.949-0.990) were independent risk factors for urinary infection stones ( P<0.05). The combined diagnostic value of six indicators was the highest, with an AUC of 0.874 (95% CI 0.837-0.911). Following this, urine pH exhibited an AUC of 0.818 (95% CI 0.778-0.858), while serum uric acid had an AUC of 0.704 (95% CI 0.652-0.756). The nomogram model was successfully constructed based on the six indicators. The mean AUC of the ROC curve after 1 000 resamples of the Bootstrap method was 0.864 (95% CI 0.828-0.900), and the calibration curve showed that the predicted curve fit the ideal curve well, with a mean absolute error of 0.005 and a Hosmer-Lemeshow test of P>0.05. Clinical decision curve analysis (DCA) showed that the model had a higher net clinical benefit when the model had a threshold probability value≥0.01. Conclusions:Urine pH and serum uric acid are closely related to urinary infection stones. A nomogram model combining these factors with gender, age, recurrent stones, and urine culture results can effectively predict the probability of infection-related stones, providing significant clinical value.

Objective:To investigate the diagnostic value of urine pH, serum uric acid and related clinical indicators in the diagnosis of urinary infection stones, and to construct a prediction nomogram.Methods:The clinical data of 432 patients with urinary calculi admitted to Xuzhou Central Hospital from August 2018 to November 2023 were retrospectively analyzed. The study included 289 males and 143 females, with an average age of (52.72±13.46) years old. Among the patients, there were 98 cases of hypertension, 67 cases of diabetes, and 100 cases of recurrent calculi. Kidney stones were present in 152 cases, ureteral stones in 242 cases, and bladder stones in 38 cases. Urine bacterial culture yielded positive results in 97 cases. According to the results of postoperative stone composition analysis, the two groups were categorized as infection and no-infection stone groups, and the differences in general data between the two groups were compared. Univariate and multivariate logistic regression analysis were conducted to assess the diagnostic value of urine pH, serum uric acid, and related clinical indicators for urinary infection stones. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the clinical significance of urine pH, serum uric acid, and combined indexes in preoperatively diagnosing urinary infection stones, as well as constructing a nomogram prediction model.Results:There were 127 cases of infection stones and 305 cases of no-infection stones. The infection stone group exhibited a higher urine pH value [7.0(6.5, 7.5) vs. 6.0(5.5, 6.5), P<0.001], lower serum uric acid levels [(301.38±70.12) vs. (358.88±88.99) μmol/L, P<0.001], a higher proportion of females [55.1%(70/127) vs. 23.9%(73/305), P<0.001], younger age [(48.36±14.83)vs. (53.12±12.61)years old, P<0.001], a higher proportion of recurrence stones [34.6 %(44/127) vs. 18.4%(56/305), P<0.001], and a higher rate of positive urine bacteria culture[29.9%(38/127)vs. 19.3%(59/305), P=0.016]and nitrite test results [18.9%(24/127)vs. 6.3%(19/305), P <0.001]. Univariate logistic regression analysis revealed that urine pH value, serum uric acid levels, gender, age, recurrent stones, urine bacterial culture, and urine nitrite were associated with urinary infection stones ( P< 0.05). Multivariate logistic regression analysis revealed that urine pH value ( OR= 4.836, 95% CI 3.342-6.997), female gender( OR=2.320, 95% CI 1.286-4.186), recurrent stones ( OR=2.225, 95% CI 1.208-4.101), positive urine bacterial culture ( OR=2.061, 95% CI 1.094-3.883), serum uric acid ( OR=0.992, 95% CI 0.949-0.989), age ( OR=0.969, 95% CI 0.949-0.990) were independent risk factors for urinary infection stones ( P<0.05). The combined diagnostic value of six indicators was the highest, with an AUC of 0.874 (95% CI 0.837-0.911). Following this, urine pH exhibited an AUC of 0.818 (95% CI 0.778-0.858), while serum uric acid had an AUC of 0.704 (95% CI 0.652-0.756). The nomogram model was successfully constructed based on the six indicators. The mean AUC of the ROC curve after 1 000 resamples of the Bootstrap method was 0.864 (95% CI 0.828-0.900), and the calibration curve showed that the predicted curve fit the ideal curve well, with a mean absolute error of 0.005 and a Hosmer-Lemeshow test of P>0.05. Clinical decision curve analysis (DCA) showed that the model had a higher net clinical benefit when the model had a threshold probability value≥0.01. Conclusions:Urine pH and serum uric acid are closely related to urinary infection stones. A nomogram model combining these factors with gender, age, recurrent stones, and urine culture results can effectively predict the probability of infection-related stones, providing significant clinical value.

BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
Humans ; Female ; Genomics ; Carcinogenesis ; Carcinoma ; Breast Neoplasms ; Cell Transformation, Neoplastic ; Nucleotides ; Tumor Microenvironment

Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).

Objective:To evaluate the clinical effect of embolization of congenital parotid arteriovenous fistula(AVF) using coils and absolute ethanol.Methods:From January 2015 to December 2019, 8 patients with congenital AVF in parotid region were admitted to the Department of Interventional Radiology Shanghai Ninth People’s Hospital. AVF was confirmed by angiography of common carotid artery and vertebral artery through femoral artery puncture with Seldinger technique. Using coaxial microcatheter to reach the fistula via artery or using direct percutaneous puncture to reach the dilated vein and introduced microcatheter to the fistula via puncture needle. Combined detachable coils with fiber coils, and used absolute ethanol to occlude the fistula. Then the outcome was evaluated.Results:There were 7 males and 1 female involved in this study. The average age was 28.5 years (3-58 years). All of the 8 patients were confirmed AVF in parotid region by angiography, five on the right and three on the left. The feeder artery was external carotid artery, and the outflow vein was external jugular vein. Among them, 6 patients used coaxial microcatheter to reach the fistula via artery, 2 patients used direct percutaneous puncture after failure via transarteral approach. All the 8 patients were treated with absolute ethanol, the total amount of which was 17.4 ml on average. After embolization, the external carotid angiography demonstrated that the fistula was completely occluded, the branches of the external carotid artery at the distal end of the fistula were normal, and there was no obvious reflux vein. After the operation, all the patients had no pulsation and tremor. The external jugular vein dilation disappeared in 4 patients. One patient had temporary facial paralysis on the same side of the operation area. The symptoms disappeared three days after treatment. This patient had undergone coils exposed three months after operation. After local debridement, the exposed coils were removed and the wound healed. The 8 patients were followed up for 6-12 months without recurrence.Conclusions:Embolization with coils combined with absolute ethanol is safe and affective treatment for congenital parotid AVF.

Objective:To evaluate the clinical effect of embolization of congenital parotid arteriovenous fistula(AVF) using coils and absolute ethanol.Methods:From January 2015 to December 2019, 8 patients with congenital AVF in parotid region were admitted to the Department of Interventional Radiology Shanghai Ninth People’s Hospital. AVF was confirmed by angiography of common carotid artery and vertebral artery through femoral artery puncture with Seldinger technique. Using coaxial microcatheter to reach the fistula via artery or using direct percutaneous puncture to reach the dilated vein and introduced microcatheter to the fistula via puncture needle. Combined detachable coils with fiber coils, and used absolute ethanol to occlude the fistula. Then the outcome was evaluated.Results:There were 7 males and 1 female involved in this study. The average age was 28.5 years (3-58 years). All of the 8 patients were confirmed AVF in parotid region by angiography, five on the right and three on the left. The feeder artery was external carotid artery, and the outflow vein was external jugular vein. Among them, 6 patients used coaxial microcatheter to reach the fistula via artery, 2 patients used direct percutaneous puncture after failure via transarteral approach. All the 8 patients were treated with absolute ethanol, the total amount of which was 17.4 ml on average. After embolization, the external carotid angiography demonstrated that the fistula was completely occluded, the branches of the external carotid artery at the distal end of the fistula were normal, and there was no obvious reflux vein. After the operation, all the patients had no pulsation and tremor. The external jugular vein dilation disappeared in 4 patients. One patient had temporary facial paralysis on the same side of the operation area. The symptoms disappeared three days after treatment. This patient had undergone coils exposed three months after operation. After local debridement, the exposed coils were removed and the wound healed. The 8 patients were followed up for 6-12 months without recurrence.Conclusions:Embolization with coils combined with absolute ethanol is safe and affective treatment for congenital parotid AVF.

Objective To evaluate the short-term curative effect and the safety of transcatheter arterial chemoembolization (TACE) therapy by using microspheres and lipiodol for hepatocellular carcinoma (HCC).Methods A total of 87 patients with pathologically proved HCC were randomly divided into the study group (n=44,using embospheres of 100-300 μm in diameter together with lipiodol) and the control group (n=43,using gelfoam particles of 350-560 μm in diameter together with lipiodol).Postopertaive biochemical (liver function and AFP) findings and imaging (CT and/or MRI) manifestations were recorded,and the clinical efficacy and adverse reactions were analyzed.Results TACE was performed in all 87 patients.After the treatment,both the disease benefit rate and the postoperative reduction in AFP level in the study group were remarkably better than those in the control group (P＜0.05),but postoperative liver function indexes were not significantly different from the preoperative ones (P＞0.05).The average number of interventional therapy within the follow-up period of 6 months in the study group was smaller than that in the control group (P＜0.05).No statistically significant differences in 6-,12-and 18-month survival rates existed between the two groups (P＞0.05).Conclusion In treating HCC,TACE by combination use of microspheres and lipiodol is safe,its short-term curative effect is more obvious than TACE by combination use of gelfoam particles and lipiodol,and it can reduce the times of interventional procedure.Before TACE,careful planning of the pre-treatment of hepatic artery-portal vein fistula and the superselective catheterization with micro catheter should be taken into consideration.