Abstract: Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in the activation of B cells and granulocytes, operating downstream of B cell and Fcγ receptors, and is considered an attractive target for treating autoimmune diseases. Preclinical investigations have demonstrated that inhibition of BTK activity holds promise as a potential therapeutic strategy for inflammatory immune responses such as autoimmune diseases and allergies. This review provides an overview of the mechanisms by which BTK contributes to immune-related diseases and summarizes current research on the development of BTK inhibitors for treating these conditions, aiming to offer novel insights into non-oncology applications for BTK inhibitors.

Abstract: The differential expression and subcellular localization of single-cell proteins are closely related to the physiological state and pathological mechanisms of the body. The development of single-cell protein in situ imaging methods provides powerful tools for spatial single-cell proteomics research and single-cell protein profiling. This article summarizes the single-cell protein imaging methods developed in recent years, including the circulating immunofluorescence imaging methods based on ordered multi-round antibody incubation, mass spectrometry imaging based on metal element labeled antibodies, fluorescence imaging based on DNA-barcoded antibody, gene encoded fluorescence protein imaging and spectral imaging based on Raman spectroscopy or X-ray spectroscopy, with brief explanation of the imaging principles of these methods. It focuses on the multiple performance, imaging resolution and signal amplification performance of these methods, and analyzes their application characteristics in practical scientific research and clinical work, in the hope of providing some reference for the development of more revolutionary single-cell imaging methods, and promoting the development of biomedical and precision medicine.

Robotic natural orifice specimen extraction surgery for right colon cancer has been conducted with progressive refinements. To facilitate the standardized implementation of this surgical technique, the adoption of rigorous quality control measures is paramount. The present article outlines the key aspects of quality control for robotic natural orifice specimen extraction right hemicolectomy surgery, encompassing the preoperative, intraoperative, and postoperative phases, as well as the training and credentialing requirements for the operating surgeons, with the aim of providing a reference framework to facilitate the safe and reliable implementation and dissemination of this minimally invasive approach for right colon cancer.

Robotic natural orifice specimen extraction surgery for right colon cancer has been conducted with progressive refinements. To facilitate the standardized implementation of this surgical technique, the adoption of rigorous quality control measures is paramount. The present article outlines the key aspects of quality control for robotic natural orifice specimen extraction right hemicolectomy surgery, encompassing the preoperative, intraoperative, and postoperative phases, as well as the training and credentialing requirements for the operating surgeons, with the aim of providing a reference framework to facilitate the safe and reliable implementation and dissemination of this minimally invasive approach for right colon cancer.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m²) vs. (60±15) mL/(min·1.73 m²), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

Bioluminescence is a widespread phenomenon in nature, and luminescent organisms can be found both on land and in the ocean. Among them, luciferase based bioluminescence systems have been widely studied, inspiring the exploration of genetic and epigenetic aspects and the development of a series of related assays for in vivo and in vitro studies. This paper summarizes the recent developments of luciferase based bioluminescence assays in terms of bioluminescence systems, types of luciferases, and the development and application of luciferase bioluminescence assays.

Objective:We employ different regimens of induction therapy in living donor ABO-incompatible kidney transplantation(ABOi-KT) recipients to compare their clinical outcomes during 6 months post-KT.Methods:A retrospective analysis was conducted for the relevant clinical data of 41 ABOi-KT recipients from June 2018 to September 2022.Thirteen recipients on induction therapy of anti-human T lymphocyte porcine immunoglobin(pATG)were enrolled in pATG group; 19 recipients on induction therapy of basiliximab in basiliximab group; 9 recipients on induction therapy of rabbit anti-human thymocyte immunoglobulin(rATG)in rATG group.Differences in age, gender, body mass index(BMI), dialysis modality/duration, sideness of donor kidney, frequency of blood group antibody treatment, dose of rituximab, basic blood group antibody titers of IgG/IgM, and the gender and BMI of recipient's donor were compared for three groups.Immune status was assessed by comparing absolute lymphocyte count before pre-treatment and within 6 months post-KT in recipients under different induction regimens among 3 groups by one-way analysis of variance.Transplant kidney function was assessed by comparing the levels of serum creatinine, estimated glomerular filtration rate(eGFR)and serum urea nitrogen using one-way analysis of variance.The incidence of delayed graft function(DGF), acute rejection(AR)and infection was compared among three groups.Results:Regarding baseline profiles, except for donor age pATG group[(60.23±6.10)years]versus basiliximab group[(51.95±6.97)years]was statistically significant( P=0.002), the differences in the remaining parameters were not statistically significant among three groups(all P>0.05). At Day 1/3/7/10/14 post-KT, absolute lymphocyte counts were(0.17±0.07)×10 9/L, (0.27±0.14)×10 9/L, (0.85±0.40)×10 9/L, (1.05±0.56)×10 9/L and(1.10±0.56)×10 9/L in pATG group and(0.69±0.04)×10 9/L, (0.18±0.21)×10 9/L, (0.57±0.44)×10 9/L, (0.67±0.45)×10 9/L and(0.81±0.46)×10 9/L in rATG group respectively.They were all higher than those in basiliximab group[(0.46±0.18)×10 9/L, (0.67±0.26)×10 9/L, (1.29±0.48)×10 9/L, (1.56±0.49)×10 9/L, (1.75±0.53)×10 9/L]and the differences were statistically significant(all P<0.05). No statistically significant difference existed in absolute lymphocyte count among 3 groups before pre-treatment and after Day 21 post-KT(all P>0.05). At Week 1/2/4/12/24 post-KT, the differences in serum levels of creatinine and urea nitrogen were not statistically significant( P>0.05). At Month 1/3 post-KT, eGFR was(47.24±14.51)and(49.94±14.31)ml·min -1·(1.73 2) -1 in rATG group and they were lower than(67.36±21.60)and(65.00±14.67)ml·min -1·(1.73 2) -1 in basiliximab group with a statistically significant difference( P<0.05). However, at Week 1/2/24 post-KT, no statistically significant difference existed in eGFR among 3 groups( P>0.05). In ATG, basiliximab and rATG groups, DGF(1 case, 1 case, 1 case), AR(2 cases, 2 cases, 1 case)and infection(4 cases, 7 cases, 3 cases)occurred during 6 months post-KT. Conclusions:Through a limited sample of single centers, no statistically significant difference existed in graft function recovery for ABOi-KT recipients on induction therapies of pATG, basiliximab and rATG.And DGF, AR and infections occurred in all three groups.However, there were little inter-group differences.

Objective:To explore the epidemiological characteristics, risk factors, preventions and treatments of recent human parvovirus B19 (HPV-B19) infections in recipients of renal transplantation (RT).Methods:From May 2020 to June 2021, retrospective review was conducted for epidemiological characteristics, treatment protocols, preventions and outcomes of HPV-B19 infected recipients after RT.Risk factors were analyzed using uninfected recipients after RT in the same period as controls.And 78 recipients who were not infected after RT with similar operation time were used as a control group for risk factor analysis.The infection rates of the four liver transplant recipients infected with HPV-B19 during the same period were calculated and compared with those of the kidney transplant recipients.Chi-square test and Fisher's exact test were used for statistical analysis.Results:During the observation period, HPV-B19 infection occurred in 39/368 recipients after RT with an overall infection rate of 10.60%(39/368). In terms of clinical symptoms, all 39 recipients presented with pure red cell aplasia (PRCA). In terms of season of infection, HPV-B19 infections occurred predominantly in autumn and winter [74.3% (29/39) of infections in autumn and winter, including 48.7% (19/39) in autumn]. Comparing the infection rates of different transplant recipients, 4 out of 123 liver transplant recipients were infected with HPV-B19 during the same period.The rate of infection was lower in liver transplant recipients than in RT counterparts (3.25% vs.10.60%, χ2=6.225, P=0.013). Analysis of OR values showed that transfusion of blood products was a risk factor for recent postoperative infection ( χ2=4.806, P=0.028, OR=2.418, 95% CI=1.088-5.373). Conclusions:HPV-B19 infection in renal transplant patients is mainly manifested as PRCA and is more likely than in liver transplant patients.Autumn and winter may be susceptible seasons for HPV-B19 and protection should be increased to prevent infection.Transfusion of blood products is a risk factor for recent HPV-B19 infection after RT, therefore donors should be routinely examined and it is imperative to test the safety of blood products in patients after RT.Thus HPV-B19 infection is well-controlled so that further spread may be prevented to avoid an epidemic outbreak.

Objective:To observe the safety and efficacy of early conversion into a simplified once-daily immunosuppressive regimen of sirolimus plus low-dose extended-release tacrolimus in kidney transplant recipients.Methods:From April 2019 to August 2020, clinical data were collected from 44 recipients (22 pairs) of kidney transplantation. Two kidneys from the same donor were randomly divided into observed and control groups. The immunosuppressive regimen of two groups was the same within 1 month post-transplantation, i. e. tacrolimus plus mycophenolatemofetil (or mycophenolate sodium) and prednisone. Then the immunosuppressive regimen of observed group was switched into a simplified once-daily regimen of sirolimus plus low-dose extended-release tacrolimus and prednisone while control group remained unchanged. The changes of graft function, proteinuria and the incidence of related adverse events were recorded.Results:No inter-group difference existed in serum level of creatinine at Month 1 post-transplantation (163.40±51.57 vs 166.10±49.48 μmol/L). After regimen conversion, serum level of creatinine was slightly lower in observed group than that in control group at Months 3 and 6 post-transplantation (130.10±30.10 vs 134.90±28.97, 121.50±24.96 vs 136.30±27.06). However, there was no statistic difference. The 24-hour urinary total trace protein was slightly higher in observed group than that in control group (331.20±84.21 vs 279.50±80.91 and 209.60±66.02 vs 179.50±37.60 mg/24 h) at Months 3 and 6 post-transplantation. However, there was no statistic difference. No inter-group difference existed in the incidence of drug side effects or other adverse events.Conclusions:In kidney transplant recipients at Month 1 post-transplantation, a conversion of immunosuppressive regimen into a simplified once-daily of sirolimus plus low-dose extended-release tacrolimus can significantly boost patient compliance without an elevated risk of drug side effects or adverse events and offer an advantage of reducing nephrotoxicity.