The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

【Objective】 To explore the effectiveness of using donor plasma reinfusion to flush the leukoreduction system (LRS) chamber during the final reinfusion phase with the Trima Accel automated blood collection system in preventing the reduction of CD4+ and CD8+ T lymphocytes. 【Methods】 A longitudinal and cross-sectional study was designed. CD4+ count<200 cells/μL and CD8+ count<125 cells/μL were considered as the criteria for deficiency. Eighteen first-time platelet donors were followed up. The lymphocyte count was measured at 0, 3-6 and 7-14 times of blood donation in the last 300 days. 170 healthy blood donors who have not donated blood were selected as the control group. According to the cut-off point(October 2021), 88 blood donors who mainly used automatic blood collection system to donate platelet apheresis in the last 365 days(median blood donation times ≥17.5)were divided into three groups(A, B and C)and blood samples were obtained. The time for Groups A, B and C started donating platelet apheresis were as follows: Group A: before October 2019, Group B: from October 2019 to September 2021, Group C: after October 2021. Blood samples were analyzed to obtain blood counts including CD4 + and CD8 + T lymphocytes. Blood samples were analyzed to obtain blood cell counts including CD4+ and CD8+ T lymphocytes. Through a comparative analysis, this study aimed to determine if there are any statistical differences in the detection indices between the follow-up groups with varying frequencies of blood donation, the control group, and groups A, B, and C. This approach was employed to infer the efficacy of donor plasma reinfusion in flushing the leukoreduction system (LRS) chamber for preventing the decline of CD4+ and CD8+ T lymphocytes. 【Results】 Eighteen first-time blood donors who were converted to regular platelet apheresis donors did not show a decrease of CD4 + and CD8 + T lymphocytes in the 5 th and 11 th blood donation (median number of blood donation), and there was no significant difference between the above indexes and those in the 0 th blood donation. Among the previous frequent blood donors, the CD4+ and CD8+ T lymphocyte counts in Group B and Group C are both higher than the standard value, showing no statistical difference from the control group. Among regular blood donors, the CD4+ and CD8+ T lymphocyte counts in groups B and C were higher than the criteria values, and had no statistical difference compared to the control group.The CD4+ T lymphocyte count in Group A was normal, with only one donor in Group A having a CD8+ T lymphocyte count below 125 cells/μL. This donor has donated 281 times of platelet apheresis, and the group he belongs to has started blood donation 2-21 years(median of 5 years) before the adjustment of reinfusion mode. The CD4+ and CD8+ T lymphocyte counts in Group A showed significant differences compared to the control group, with median counts (Group A/Control Group) of 359/521 and 257/372, respectively, P<0.001. In Group A, 0%(0/35) had a CD4+ count below 200 cells/μL, and 2.85%(1/35) of donors had a CD8+ count below 125 cells/μL, which was far lower than the proportion of CD4+ and CD8+ T cell deficiency found in regular apheresis donors by John M. Gansner and Mahboubeh Rahmani. The study showed that the adjustment of the plasma reinfusion mode did not further reduce the T lymphocyte counts in blood donors, but instead further restored the T lymphocyte counts in regular blood donors. This indicated that after the adjustment of plasma reinfusion mode, blood donors might not have lost CD4+ and CD8+ T lymphocytes during blood donation, or only lost a small amount, and can recover even if they donate platelet apheresis frequently. 【Conclusion】 Trima Accel automated blood collection system has a good effect on preventing CD4 + and CD8 + T lymphocytes from being reduced by flushing the LRS chamber with donor plasma.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Objective:To explore the feasibility and clinical effects of unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap in repairing huge pressure ulcers in the sacrococcygeal region.Methods:The study was a retrospective observational study. From June 2020 to April 2023, 15 patients with stage Ⅳ pressure ulcers with sacrococcygeal defect area greater than 10.0 cm×10.0 cm who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 8 males and 7 females, aged from 30 to 86 years. The pressure ulcers before debridement were all accompanied by different degree of infection and necrosis. Debridement and negative pressure sealing and irrigation treatment were performed in stage Ⅰ. After debridement, the skin and soft tissue defect area was 12.0 cm×10.5 cm to 20.0 cm×17.0 cm. After the wound bed infection was controlled, unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap was used to repair the pressure ulcer wounds in stage Ⅱ. The perforator flap area was 12.0 cm×7.0 cm to 16.0 cm×10.5 cm. The donor area wound was sutured directly. After operation, the survival, complications, and wound healing of flap donor area were observed. During regular follow-up, the recurrence of pressure ulcers, the appearance and texture of the flap, and the scars in the donor site were observed.Results:After operation, 1 patient had fluid accumulation under the flap and survived after drainage and dressing change. The flaps of the other patients survived well without infection, local necrosis, and sinus formation under the flap. The wounds in the donor area healed well. All patients were followed up for more than 6 months, and there was no recurrence of pressure ulcers. The appearance of the flap was not bloated, the texture was soft, and the compression resistance and elasticity were good. The donor site wound healed well without obvious scar.Conclusions:The surgical method of repairing giant sacrococcygeal pressure ulcers with unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap is simple and easy to operate. It can repair large defect area with the donor area being sutured directly, which is worthy of clinical promotion.

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.

Machine Learning ; Image Processing, Computer-Assisted/methods*