AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective: To investigate the protective effects and mechanisms of acellular nerve allografts (ANA) on motor neurons in the spinal cord anterior horn of sciatic nerve injury ( SNI) rats . Methods: SPF grade male SD rats were randomly divided into normal , model , ANA-bridged (bridge group) , and autologous nerve transplantation groups (autograft group) , with 6 rats in each group . The SNI rat model was established using the right sciatic nerve clamp method for 10 mm . In the bridge group , the ANA was bridged to the two severed ends of the injured sciatic nerve , and in the autograft group , the autologous nerves were flipped head to tail and then bridged to the two se- vered ends . A spectrophotometer was applied to determine the DNA content in normal nerves and ANA . The foot- print test was used to determine the sciatic nerve function index (SFI) of the rats in each group , the wet weight ra- tio of the anterior tibialis muscle was calculated . The morphology and structure of the anterior horn motor neurons of the spinal cord of each group were observed by HE staining. The immunofluorescence and Western blot were used to detect Apaf-1 , Caspase-3 , Bcl-2 , Bax , and Cyt-C proteins expression in the L4-6 segment of the spinal cord . Results: The DNA content in the ANA prepared in this study was significantly lower than that in normal nerves (P < 0. 05) . Compared with the normal group , the SFI and wet weight ratio of the anterior tibialis muscle were re- duced in the model group (P < 0. 001) ; compared with the model group , both SFI and wet weight ratio of the ante- rior tibialis muscle significantly increased in the bridge group and the autografts group ( P < 0. 05 , P < 0. 001) , and the SFI and wet weight ratio of the anterior tibialis muscle in the autograft group were higher than those in the bridge group (P < 0. 001 , P < 0. 01) . The results of HE staining showed that the motor neurons in the anterior horn of the spinal cord of the normal group were structurally intact and had clear cytosolic boundaries; the neurons in the model group were lysed and necrotic , with blurred cytosolic boundaries; the neurons in the bridge group were less lysed and necrotic , but the nuclear translocation phenomenon could still be seen; the neurons in the autograft group were morphologically and structurally intact with clear cytosolic boundaries . Compared with the normal group , the expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins significantly increased in the model group (P < 0. 001 , P < 0. 01 , P < 0. 01 , P < 0. 05) . Compared with the model group , the expression of Apaf-1 , Caspase- 3 , Bax , and Cyt-C proteins significantly decreased (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) ; but the expres- sion of Bcl-2 protein significantly increased in the bridge group and the autograft group (P < 0. 05) . The expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins in the autografts group was lower than that in the bridge group (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) . Conclusion ANA can exert a protective effect on motor neurons in the anterior horn of the spinal cord of SNI rats by improving the morphology and structure of neurons , increasing the ex- pression of Bcl-2 protein , but decreasing the expression of Cyt-C , Bax , Caspase-3 , and Apaf-1 proteins in the spi- nal cord . The mechanism of ANA may be related to the Bcl-2/Cyt-C/Apaf-1-mediated mitochondrial apoptosis sig- naling pathway .

Objective:To evaluate the efficacy of modified splenic arteriovenous shunt surgery at the distal pancreatic tail in combined pancreas-kidney transplantation.Methods:A retrospective analysis was conducted on 24 recipients who underwent combined pancreas-kidney transplantation with the modified splenic arteriovenous shunt at the pancreatic tail from November 2023 to October 2024 (shunt group) and 231 recipients who received conventional splenic artery and vein ligation since 2016 (ligation group). The incidence of perioperative thrombosis and severe adverse events was compared between the two groups using the chi-square test or Fisher's exact test. Independent sample t-tests were performed to assess postoperative pancreatic and renal function recovery as well as blood perfusion in 15 recipients from the shunt group and 20 from the ligation group who underwent CT perfusion imaging (CTP).Results:The incidence of perioperative splenic arteriovenous thrombosis was lower in the shunt group (0) compared to the ligation group (4.76%, 11/231), though the difference was not statistically significant ( P=0.606). One month postoperatively, the shunt group demonstrated significantly lower serum amylase levels than the ligation group (99.61±19.62 vs. 148.20±70.67 U/L, P=0.018). However, at the time of CTP examination, serum lipase (67.87±32.35 vs. 45.11±17.94 U/L, P=0.014) and creatinine levels (131.79±26.41 vs. 112.1±24.98 μmol/L, P=0.034) were significantly higher in the shunt group. Urea nitrogen levels were also significantly higher in the shunt group both one month postoperatively (11.24±4.64 vs. 8.51±3.01 mmol/L, P=0.043) and at the CTP examination (10.41±1.78 vs. 6.87±1.91 mmol/L, P=0.001). Regarding pancreatic perfusion, blood volume in both the pancreatic head (15.99 ± 3.51 vs. 20.67 ± 5.47 ml/100 g, P = 0.024) and tail (17.19±4.24 vs. 27.40±19.80 ml/100 g, P=0.039) was significantly lower in the shunt group. After one minute of splenic artery perfusion, the shunt group exhibited significantly higher splenic artery blood flow (755.85±101.50 vs. 574.00 ± 142.06 ml·min -1· (100 g) -1, P<0.001) and blood volume (58.90 ±19.93 vs. 23.21±17.02 ml/100 g, P=0.007) compared to the ligation group. These differences persisted after two minutes of perfusion (blood flow: 793.83±68.57 vs. 503.78 ± 130.80 ml·min -1· (100 g) -1, P<0.001; blood volume: 64.22±15.74 vs. 34.32±20.39 ml/100 g, P=0.002). For the transplanted kidney, the shunt group had significantly lower blood flow (113.10±28.55 vs. 232.76±113.37 ml·min -1· (100 g) -1, P<0.001), blood volume (28.95±10.79 vs. 38.36±12.38 ml/100 g, P=0.047), and capillary surface permeability (PS) (26.49±16.57 vs. 43.02±20.37, P = 0.042) in the upper pole. Similar reductions in blood flow, blood volume, and PS were observed in the middle dorsal region ( P=0.018, 0.021, and 0.048, respectively) and lower pole ( P<0.001, P=0.048, and P=0.012, respectively). Conclusion:The modified splenic arteriovenous shunt at the pancreatic tail appears to be a safe and effective approach to reducing the risk of pancreatic graft thrombosis. This technique facilitates effective diversion of pancreatic parenchymal blood flow into the splenic vein, alleviating hyperperfusion of the transplanted pancreas. While renal blood perfusion was reduced postoperatively, it did not adversely affect renal function.

Objective:To evaluate the efficacy of modified splenic arteriovenous shunt surgery at the distal pancreatic tail in combined pancreas-kidney transplantation.Methods:A retrospective analysis was conducted on 24 recipients who underwent combined pancreas-kidney transplantation with the modified splenic arteriovenous shunt at the pancreatic tail from November 2023 to October 2024 (shunt group) and 231 recipients who received conventional splenic artery and vein ligation since 2016 (ligation group). The incidence of perioperative thrombosis and severe adverse events was compared between the two groups using the chi-square test or Fisher's exact test. Independent sample t-tests were performed to assess postoperative pancreatic and renal function recovery as well as blood perfusion in 15 recipients from the shunt group and 20 from the ligation group who underwent CT perfusion imaging (CTP).Results:The incidence of perioperative splenic arteriovenous thrombosis was lower in the shunt group (0) compared to the ligation group (4.76%, 11/231), though the difference was not statistically significant ( P=0.606). One month postoperatively, the shunt group demonstrated significantly lower serum amylase levels than the ligation group (99.61±19.62 vs. 148.20±70.67 U/L, P=0.018). However, at the time of CTP examination, serum lipase (67.87±32.35 vs. 45.11±17.94 U/L, P=0.014) and creatinine levels (131.79±26.41 vs. 112.1±24.98 μmol/L, P=0.034) were significantly higher in the shunt group. Urea nitrogen levels were also significantly higher in the shunt group both one month postoperatively (11.24±4.64 vs. 8.51±3.01 mmol/L, P=0.043) and at the CTP examination (10.41±1.78 vs. 6.87±1.91 mmol/L, P=0.001). Regarding pancreatic perfusion, blood volume in both the pancreatic head (15.99 ± 3.51 vs. 20.67 ± 5.47 ml/100 g, P = 0.024) and tail (17.19±4.24 vs. 27.40±19.80 ml/100 g, P=0.039) was significantly lower in the shunt group. After one minute of splenic artery perfusion, the shunt group exhibited significantly higher splenic artery blood flow (755.85±101.50 vs. 574.00 ± 142.06 ml·min -1· (100 g) -1, P<0.001) and blood volume (58.90 ±19.93 vs. 23.21±17.02 ml/100 g, P=0.007) compared to the ligation group. These differences persisted after two minutes of perfusion (blood flow: 793.83±68.57 vs. 503.78 ± 130.80 ml·min -1· (100 g) -1, P<0.001; blood volume: 64.22±15.74 vs. 34.32±20.39 ml/100 g, P=0.002). For the transplanted kidney, the shunt group had significantly lower blood flow (113.10±28.55 vs. 232.76±113.37 ml·min -1· (100 g) -1, P<0.001), blood volume (28.95±10.79 vs. 38.36±12.38 ml/100 g, P=0.047), and capillary surface permeability (PS) (26.49±16.57 vs. 43.02±20.37, P = 0.042) in the upper pole. Similar reductions in blood flow, blood volume, and PS were observed in the middle dorsal region ( P=0.018, 0.021, and 0.048, respectively) and lower pole ( P<0.001, P=0.048, and P=0.012, respectively). Conclusion:The modified splenic arteriovenous shunt at the pancreatic tail appears to be a safe and effective approach to reducing the risk of pancreatic graft thrombosis. This technique facilitates effective diversion of pancreatic parenchymal blood flow into the splenic vein, alleviating hyperperfusion of the transplanted pancreas. While renal blood perfusion was reduced postoperatively, it did not adversely affect renal function.

Objective To explore the changes in cerebral blood flow caused by mandibular retrusion,as well as the impact and potential mechanisms on stroke recovery.Methods 6-week-old SD male rats were selected as experi-mental subjects.The metal cannula was bonded to the rat maxillary incisor for one week,forcing mandibular retru-sion(MR).Cerebral blood flow was detected by laser speckle imaging.Cognitive function was detected by the Morris water.Then,the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO)method for one week.Meanwhile,metal cannulae were then removed in rats to restore the lower jaw's position(MCAO RO),serving as a positive control group.Consequently,rats were randomly divided into the fol-lowing groups:Sham groups,MCAO groups,MCAO MR groups,and MCAO RO groups.Neurological recovery was assessed through the modified neurological severity score(mNSS).The area of cerebral infarction was evalua-ted by using triphenyltetrazolium(TTC)staining.The changes in nerve cells were observed by using hematoxylin eosin(HE)staining.The protein expression level of vascular endothelial growth factor(VEGF)was detected by immunohistochemistry.The protein expression levels of platelet-endothelial cell adhesion molecule(CD31),sirtuin 6(SIRT6),and thioredoxin interaction protein(TXNIP)were detected by Western blot.The mRNA expression levels of SIRT6,TXNIP,and VEGF were determined by qRT-PCR.Microglia activation marker molecule 1(IBA-1)was detected by immunofluorescence.Resluts Because of mandibular retrusion,laser speckle showed de-creased cerebral blood flow,and the water maze showed decreased cognitive function.Compared to other groups,MCAO MR showed a larger ischemic area in TTC staining,while HE staining and neurological scoring showed poo-rer neurological function recovery.Western blot and qRT-PCR showed that the MCAO MR group inhibited the mR-NA and protein expression levels of SIRT6,upregulated the mRNA and protein expression levels of TXNIP,and in-creased the activation of microglia.Conclusion Mandibular retrusion reduces cerebral blood flow and alters cogni-tive function in rats.Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

Background: To enhance perioperative outcomes, a perioperative registry that integrates high-quality real-world data throughout the perioperative period is essential. Singapore General Hospital established the Perioperative and Anesthesia Subject Area Registry (PASAR) to unify data from the preoperative, intraoperative, and postoperative stages. This study presents the methodology employed to create this database. Methods: Since 2016, data from surgical patients have been collected from the hospital electronic medical record systems, de-identified, and stored securely in compliance with privacy and data protection laws. As a representative sample, data from initiation in 2016 to December 2022 were collected. Results: As of December 2022, PASAR data comprise 26 tables, encompassing 153,312 patient admissions and 168,977 operation sessions. For this period, the median age of the patients was 60.0 years, sex distribution was balanced, and the majority were Chinese. Hypertension and cardiovascular comorbidities were also prevalent. Information including operation type and time, intensive care unit (ICU) length of stay, and 30-day and 1-year mortality rates were collected. Emergency surgeries resulted in longer ICU stays, but shorter operation times than elective surgeries. Conclusions The PASAR provides a comprehensive and automated approach to gathering high-quality perioperative patient data.

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

Objective:To explore the clinical efficacy of aspirin plus low molecule heparin for pancreatic thrombosis during simultaneous pancreas and kidney transplantation (SPK).Methods:A total of 129 patients aged 18 years or higher underwent SPK between September 2016 and March 2020.They were divided retrospectively into two groups of aspirin ( n=60) and heparin ( n=69) according to different anticoagulant regimens.The aspirin group received only aspirin 100 mg/d at Day 1 post-operation.The heparin group received subcutaneous injection of enoxaparin 2 000 AxaIU daily for 7 days and followed by aspirin and clopidogrel.Outcomes and complication rates were compared between two groups. Results:All operations were successful without any mortality.In aspirin group, there were 5 cases of pancreatic thrombosis and one patient underwent pancreatectomy.There was no pancreatic thrombosis in heparin group ( P=0.014). There were 8 cases of intestinal anastomotic bleeding in aspirin group and 19 cases in heparin group.Statistically significant inter-group difference existed ( P=0.048). However, no significant inter-group difference existed in delayed recovery or rejection. Conclusions:Heparin anticoagulation can significantly lower the incidence of pancreatic thrombosis after SPK.Despite a higher incidence of intestinal anastomotic bleeding, no serious complication occurs after conservative meaures.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult