Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective: To analyze the epidemiological characteristics of typhus in China from 1950 to 2021, and discuss the challenges in typhus prevention and control in China and suggest future prevention and control strategies. Methods: Based on the reported data of typhus from 1950 to 2021 in China from the Infectious Disease History Database of China Public Health Science Data Center and the National Notifiable Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, we conducted a descriptive statistical analysis. Mann-Kendall test and circular distribution method were used to analyze the incidence, mortality and case fatality of typhus to reveal the temporal, spatial and population distributions and diagnosis of typhus in China. Results: From 1950 to 2021, a total of 452 965 typhus cases and 7 339 typhus deaths were reported in China, with the cases numbers exceeding 10 000 in 14 years of the 1950s, 1960s and 1980s, respectively. Since 1990s, the reported cases and incidence rate of typhus have decreased dramatically and the most cases were sporadic. However, the reported typhus cases in Anhui, Hubei, Hunan Provinces showed significant uptrends. Although typhus could occur all the year round, but the seasonality was observed with the incidence mainly in summer and autumn. For different provinces from the north to the south, the peaks of typhus' monthly incidence tended to shift to earlier dates. The male to female ratio of the cases was 1.01∶1 (18 529∶18 366). However, more cases occurred in women in recent years. The cases aged ≤9 years accounted for the highest proportion (18.9%), but the number of cases aged ≥50 years showed an upward trend. Most cases were farmers with the proportion increasing year by year. Moreover, the cases in students and scattered-living children also accounted for relatively higher proportions. The median of the interval between onset and diagnosis of typhus was 6 days. Most cases were clinically diagnosed, while the proportion of laboratory-confirmed cases was low and most laboratory cases were confirmed by Well-Felix reaction. Conclusions: Although the incidence and mortality of typhus in China has decreased significantly, the risk for local typhus outbreaks still exists. The prevention and control of typhus still face many challenges. It is indispensable to strengthen the pathogen detection and surveillance for typhus in China.
Child ; Humans ; Male ; Female ; Scrub Typhus/epidemiology* ; Typhus, Epidemic Louse-Borne/epidemiology* ; China/epidemiology* ; Incidence ; Disease Notification

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.
Animals ; Cytochrome P-450 Enzyme System/genetics* ; Drugs, Chinese Herbal ; Glycyrrhiza ; Liver ; Male ; Plant Extracts ; Rats ; Rats, Sprague-Dawley ; Terminalia

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies

Objective: To study the effects of superficial temporal artery and vein as recipient vessels for the free anterolateral thigh flap on the appearance and functions after maxillectomy. Methods: Clinical data of 21 patients with malignant maxillary tumors in Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University from January 2014 to November 2019, who were treated by free anterolateral thigh flap with temporal superficial vessels as the recipient vessels were analyzed retrospectively. There were 18 males and 3 females, with the age ranging from 29 to 73 years old, including 19 cases of squamous carcinoma, 1 case of adenoid cystic carcinoma and 1 case of osteosarcoma. Of those 7 patients underwent primary surgery, 14 patients received resurgery, and 6 patients had a history of postoperative radiotherapy and chemotherapy. Among 14 patients with resurgery, 13 had recurrent ipsilateral second site tumor and 1 had recurrent tumor, and all of them received the maxillectomy and reconstructive surgery with the free anterolateral thigh flap. Patients were evaluated with water swallow test and speech intelligibility score in 1, 3 and 6 months after operation. The data were statistically analyzed with SPSS 22.0 statistical software. Water swallow test results before and after operation were compared using the Wilcoxon rank sum test. The mean speech intelligibility scores before and after operation were compared by the paired t test. Results: Patients were followed up for 10-60 months. All free flaps survived after operation. No diplopia occurred. Breathing, swallowing and speaking functions were normal. No movement disorders caused by the donor of thigh flap. Water swallow test showed no phenomenon of water flowing into the nasal cavity or oral and nasal leakage with level Ⅰ for 4 cases, level Ⅱ for 13 cases, level Ⅲ for 3 cases and level Ⅳ for 1 case. The mean speech intelligibility scores before surgery and 1, 3 and 6 months after surgery were 4.31±0.13, 1.46±0.21, 2.15±0.45 and 2.87±0.76 respectively. There was statistically significant difference in the mean speech intelligibility scores between 1 and 6 months after surgery (F=78.456, P<0.05). Conclusion: It is safe and reliable to use the superficial temporal vessels as recipient vessels for free anterolateral thigh flap in the reconstruction of defect after maxillectomy in malignant tumors, with good outcomes of functions and a satisfactory restoration of outward appearance.
Adult ; Aged ; Female ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Thigh/surgery*

Objective:To explore the compatibility of Panlongqi tablets in the treatment of osteoarthritis. Method:Network pharmacology was used to predict and screen the targets and pathways related to osteoarthritis of 59 compounds in Panlongqi tablets including activating blood circulation and removing stasis group（ACRG），expelling wind-damp group（EWDG）and tonifying liver and kidney group（TLKG）. Through data integration analysis, the characteristics and compatibility rules of this prescription in preventing and treating osteoarthritis were analyzed. Result:The 59 compounds can act on 70 osteoarthritis(OA) related targets, mainly involving inflammatory stimulation response, cell proliferation, cell metabolism, immune regulation and other related processes. Pathway enrichment analysis involved inflammatory response, cartilage degeneration, immune regulation, bone metabolism and other related pathways. Conclusion:The three drugs play different regulatory roles in the pathogenesis of OA, such as inflammation, chondrocyte apoptosis and metabolism, extracellular matrix degradation, and bone metabolism. Among them, promoting blood circulation and removing blood stasis were mainly related to anti-inflammatory and analgesia, the wind-dampening group was mainly involved in regulating immunity and inflammation, and the liver-kidney group was more related to bone metabolism and chondrocyte apoptosis.