Objective:To evaluate the effect of cathepsin B(CTSB)/NOD-like receptor pyrin domain containing 3(NLRP3)pathway on the polarization of macrophages induced by LPS.Methods:The well-growing RAW264.7 mouse mononuclear macrophage lines were cultured in vitro and divided into 3 groups(n=6)according to the random number table method:control group(C group),LPS group(L group)and LPS+CA074-me(CTSB inhibitors)group(B group).C group was cultured normally for 24 h,L group was cultured with LPS concentration of 1 μg/ml medium for 24 h.B group was pretreated with CTSB inhibitor CA074-me 30 μmol/L for 1 h before LPS induction,and co-cultured with LPS concentration of 1 μg/ml medium for 24 h.After 24 hours,the morphological changes of the cells were observed by microscope,the concentrations of IL-1β and IL-18 in the supernatant were determined by ELISA.The ex-pressions of cathepsin B precursor(pro-CTSB),mature cathepsin B(mature-CTSB),NLRP3,apoptosis-related speck protein(ASC)and apoptosis-related speck protein-1(caspase-1)were detected by Western blot.The mRNA expression levels of CD32,inducible ni-tric oxide synthase(iNOS),arginase 1(Arg-1)and CD206 were detected by qRT-PCR.The positive expression rates of M1 macro-phage surface marker CD86 and M2 macrophage surface marker CD206 were detected by flow cytometry.Results:Compared with group C,the morphology of cells in groups L and B became larger and pseudopodia appeared.The concentrations of IL-1β and IL-18 in cell supernatant were increased,the expressions of pro-CTSB,mature-CTSB,NLRP3,ASC and caspase-1 were increased,and the expressions of CD32,iNOS mRNA were up-regulated and the positive rates of CD86 and CD206 were increased(P<0.01).Arg-1 and CD206 mRNA in group B were up-regulated(P<0.01).Compared with group L,the pseudopodia of group B were reduced,and the morphology was closer to group C.The concentration of IL-1β and IL-18 in the supernatant,the expression of mature-CTSB,NLRP3,ASC and caspase-1,CD32 and iNOS mRNA and the positive rate of CD86 were down-regulated in group B.The expression of pro-CTSB,Arg-1 and CD206 mRNA and the positive rate of CD206 were increased(P<0.01).Conclusion:Inhibition of CTSB/NLRP3 pathway can reduce the inflammatory response,reduce the LPS-induced polarization of RAW264.7 cells to M1 macrophages,and pro-mote their polarization to M2 macrophages.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To evaluate the effect of cathepsin B(CTSB)/NOD-like receptor pyrin domain containing 3(NLRP3)pathway on the polarization of macrophages induced by LPS.Methods:The well-growing RAW264.7 mouse mononuclear macrophage lines were cultured in vitro and divided into 3 groups(n=6)according to the random number table method:control group(C group),LPS group(L group)and LPS+CA074-me(CTSB inhibitors)group(B group).C group was cultured normally for 24 h,L group was cultured with LPS concentration of 1 μg/ml medium for 24 h.B group was pretreated with CTSB inhibitor CA074-me 30 μmol/L for 1 h before LPS induction,and co-cultured with LPS concentration of 1 μg/ml medium for 24 h.After 24 hours,the morphological changes of the cells were observed by microscope,the concentrations of IL-1β and IL-18 in the supernatant were determined by ELISA.The ex-pressions of cathepsin B precursor(pro-CTSB),mature cathepsin B(mature-CTSB),NLRP3,apoptosis-related speck protein(ASC)and apoptosis-related speck protein-1(caspase-1)were detected by Western blot.The mRNA expression levels of CD32,inducible ni-tric oxide synthase(iNOS),arginase 1(Arg-1)and CD206 were detected by qRT-PCR.The positive expression rates of M1 macro-phage surface marker CD86 and M2 macrophage surface marker CD206 were detected by flow cytometry.Results:Compared with group C,the morphology of cells in groups L and B became larger and pseudopodia appeared.The concentrations of IL-1β and IL-18 in cell supernatant were increased,the expressions of pro-CTSB,mature-CTSB,NLRP3,ASC and caspase-1 were increased,and the expressions of CD32,iNOS mRNA were up-regulated and the positive rates of CD86 and CD206 were increased(P<0.01).Arg-1 and CD206 mRNA in group B were up-regulated(P<0.01).Compared with group L,the pseudopodia of group B were reduced,and the morphology was closer to group C.The concentration of IL-1β and IL-18 in the supernatant,the expression of mature-CTSB,NLRP3,ASC and caspase-1,CD32 and iNOS mRNA and the positive rate of CD86 were down-regulated in group B.The expression of pro-CTSB,Arg-1 and CD206 mRNA and the positive rate of CD206 were increased(P<0.01).Conclusion:Inhibition of CTSB/NLRP3 pathway can reduce the inflammatory response,reduce the LPS-induced polarization of RAW264.7 cells to M1 macrophages,and pro-mote their polarization to M2 macrophages.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

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.

Malignant peripheral nerve sheath tumor (MPNST) is a rare neurogenic malignant tumor. MPNST has aty-pical clinical symptoms and imaging presentations, difficult diagnosis, a high degree of malignancy, and poor prognosis. It usually occurs in the trunk, approximately 20% in the head and neck, and rarely in the mouth. This paper reports a case of MPNST of the tongue. A summary of the clinical features, diagnosis, and treatment of MPNST is presented in combination with a literature review to provide a reference for the diagnosis and treatment of this disease.
Humans ; Nerve Sheath Neoplasms/pathology* ; Neurofibrosarcoma ; Tongue/pathology*

Delayed endolymphatic hydrops （DEH） is a rare disease that causes vertigo and is often misdiagnosed as other vertigo diseases. This article reports on a patient with vertigo who was easily misdiagnosed. The patient was a middle ear cholesteatoma complicated by labyrinthine fistula （LF）; however, his vertigo was episodic vertigo, which could not be explained solely by LF causing labyrinthitis. The possibility of endolymphatic hydrops was suspected, which was confirmed by inner ear magnetic resonance gadolinium imaging. This is the first reported case of middle ear cholesteatoma complicated by LF and DEH. The patient underwent surgical resection of the cholesteatoma and three semicircular canal obstructions at the same time. During two years postoperative follow-up, the patient did not experience a recurrence of vertigo. When diagnosing vertigo diseases, a careful history of vertigo is of utmost importance.
Humans ; Endolymphatic Hydrops/diagnosis* ; Cholesteatoma, Middle Ear/complications* ; Vertigo/complications* ; Labyrinth Diseases/complications* ; Magnetic Resonance Imaging/adverse effects* ; Semicircular Canals

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 application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC).Methods:Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People′s Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed.Results:(1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA 125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H ( P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences ( P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference ( P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion:TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.

Objective:To investigate the clinical significance of the primary tumor size in patients with endometrial carcinoma (EC).Methods:A total of 385 patients with EC admitted to Peking University People's Hospital from January 2006 to December 2016 with complete follow up data were selected, whose tumor size data before biopsy were retrospectively studied.Results:(1) The mean diameter of the primary tumor was (3.6±1.8) cm (range: 1-15 cm). And 48 cases were 0-<2 cm, 78 cases were 2-<3 cm, 92 cases were 3-<4 cm, 73 cases were 4-<5 cm, 94 cases were ≥5 cm. The diameter of the tumor was associated with age <60 years old, premenopause, CA 125≥35 kU/L, non-parturition, poor differentiation, stage Ⅲ-Ⅳ, depth of myometrial infiltration ≥1/2, cervical interstitial involvement, adnexal metastasis and lymph node metastasis (all P<0.05), but not associated with body mass index, hypertension, diabetes mellitus, pathology, lymph-vascular space invasion (all P>0.05). (2) Among the 334 patients underwent lymphadenectomy, 45 (13.5%, 45/334) cases with lymph node metastasis were observed. Stratified analysis showed that lymph node metastasis and recurrence rate of patients with EC gradually increased with the increase of tumor size ( P<0.05). Adopting 2, 3, 4 and 5 cm as cut-off values of tumor size, there were significant differences in the rate of lymph node metastasis and recurrence among them observed ( P<0.05), except for lymph node metastasis rate and recurrence rate when the cut-off value was 2 cm ( P>0.05). (3) An receiver operating characteristic (ROC) curve analysis showed that a tumor diameter of 4.25 cm was the cut-off prognostic value to predict lymph node metastasis and recurrence of EC. Conclusions:Tumor diameter is significantly correlated with lymph node metastasis and recurrence in patients with EC. Tumor size should be considered in determining the scope of surgery and adjuvant therapy.