ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Objective To compare the efficacy of renal proximal renal artery denervation(pRDN)and full-length renal artery denervation(fRDN)for treatment of hypertension.Methods Fifty-six hypertensive patients were enrolled and randomly assigned to full-length renal artery denervation group(n=25)and proximal renal artery denervation group(n=31).After the procedure,24-hour ambulatory blood pressure monitoring(24 h-ABPM)at 6 months and office blood pressure at 12 months was recorded for statistical analysis.Results The blood pressure at follow-up reduced significantly in both groups,while there was no significant difference between groups.The baseline office blood pressure in fRDN group and pRDN group was(180±15)/(104±10)mmHg and(180±12)/(103±8)mmHg,respectively,which decreased to(142±9)/(82±7)mmHg and(143±10)/(83±6)mmHg at 12 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).The baseline 24 h-ABPM in the two groups was(162±13)/(95±8)mmHg and(160±12)/(94±8)mmHg,respectively,which decreased to(142±11)/(83±7)mmHg and(141±8)/(81±7)mmHg at 6 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).However,there was no significant difference in the reduction of office blood pressure and ambulatory blood pressure between the two groups.No treatment-related adverse events were observed.Conclusions pRDN has similar antihypertensive effect to fRDN.

Objective To explore the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP),and reveal its mechanism of resistance to ceftazidime/avibactam(CZA).Methods CZA-re-sistant CRKP strains initially isolated from the Affiliated Hospital of Xuzhou Medical University from January 2021 to September 2023 were collected.The carriage of 5 carbapenemase genes(blaKPC,blaNDM,blaOXA,blaVIM,blaIMp)were detected with gene amplification method and colloidal gold method.The relative copy number and expression level of Klebsiella pneumoniae(KP)carbapenemase-producing KP(KPC-KP)was detected with real-time quantita-tive polymerase chain reaction(RT-qPCR),mutation sites of KPC mutation strains were analyzed with whole-ge-nome sequencing,and epidemic characteristics of CRKP and resistance mechanism to CZA were analyzed.Results A total of 73 CZA-resistant CRKP strains were isolated,with 37(50.68％)being KPC and NDM co-producing strains,33(45.21％)NDM-producing alone(23 strains producing NDM-5 and 10 strains producing NDM-1),and 3 KPC-producing alone.KP-2842 strain was identified as ST11-type KPC-33 variant,KP-2127 and KP-2189 strains produced KPC-2.Compared with KP ATCC BAA-1705,the copy number of blaKPC in these strains up-regulated by 1.04-3.86 fold,and the expression increased by 6.66-12.93 fold,respectively.Colloidal gold and PCR methods demonstrated good consistency and the ability to detect the enzyme co-producing and KPC-33 variant.Conclusion In this hospital,the resistance of CRKP to CZA is primarily mediated by the metalloenzyme NDM,with co-produc-tion of NDM and KPC being a characteristic of CRKP.High copy number and expression level of blaKPC-2 also con-tribute to CZA resistance.This study identified the KPC-33 variant for the first time in ST11-type CRKP in Jiangsu Province.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.

Epidemiological data and clinical characteristics of patients with tick-borne diseases were analyzed to improve diagnosis and treatment outcomes.The data of 32 patients(epidemiology and clinical characteristics)treated for tick-borne diseases at Beijing Ditan Hospital from January 2013 to June 2023 were retrospectively reviewed.Of the 32 patients,17 were diagnosed with severe fever with thrombocytopenia syndrome(SFTS),5 with Lyme disease,and 10 with rick-ettsial disease.Disease was concentrated from May to Octo-ber each year.There were 14 local cases in Beijing(43.8％),with Pinggu District accounting for the highest proportion(4 cases,28.6％),16 imported cases from other provinces(50.0％),and 2 cases(6.3％)from people living abroad.The median time from disease onset to hospitalization was 8 days and the median length of hospitalization was 10 days.The mean age of patients with tick-borne diseases was 50.16±14.61(range,21-80)years.By occupation,farmers were at the greatest risk of tick-borne diseases(14 cases,43.8％).Erythema migrans(EM)was a typical skin lesion characteristic of Lyme disease,and fever was seen in all three groups,but mainly in patients with SFTS and rickettsial disease,who mainly presented with moderate fever.Decreased WBC and NEUT counts were most commonly seen in SFTS,whereas no WBC ab-normality was seen in patients with Lyme disease.Decreased EOS counts were seen in both SFTS and rickettsial disease,whereas no abnormality was seen in Lyme disease.Decreased PLT counts were typical of SFTS.Patients with rickettsial disease and SFTS showed significant liver damage with markedly elevated ALT and AST levels.Significant myocardial damage with ele-vated CK and CK-MB levels was seen in SFTS.Elevated CRP was mainly seen in rickettsial disease.Elevated PCT counts were mostly seen in rickettsial infections,followed by SFTS.The incidence of tick-borne diseases in Beijing continues to increase an-nually.Since diagnosis is often delayed,vigilant surveillance is key to improve diagnosis.Therefore,detailed epidemiological in-formation of each tick-borne disease based on clinical characteristics is needed to ensure early diagnosis and treatment.

OBJECTIVE: To establish and modify quantitative real-time polymerase chain reaction (qPCR)-based serotyping assays to distinguish 97 pneumococcal serotypes. METHODS: A database of capsular polysaccharide ( cps) loci sequences was generated, covering 97 pneumococcal serotypes. Bioinformatics analyses were performed to identify the cps loci structure and target genes related to different pneumococcal serotypes with specific SNPs. A total of 27 novel qPCR serotyping assay primers and probes were established based on qPCR, while 27 recombinant plasmids containing serotype-specific DNA sequence fragments were constructed as reference target sequences to examine the specificity and sensitivity of the qPCR assay. A panel of pneumococcal reference strains was employed to evaluate the capability of pneumococcal serotyping. RESULTS: A total of 97 pneumococcal serotyping assays based on qPCR were established and modified, which included 64 serotypes previously reported as well as an additional 33 serotypes. Twenty-seven novel qPCR serotyping target sequences were implemented in the pneumococcal qPCR serotyping system. A total of 97 pneumococcal serotypes, which included 52 individual serotypes and 45 serotypes belonging to 20 serogroups, could not be identified as individual serotypes. The sensitivity of qPCR assays based on 27 target sequences was 1-100 copies/µL. The specificity of the qPCR assays was 100%, which were tested by a panel of 90 serotypes of the pneumococcal reference strains. CONCLUSION A total of 27 novel qPCR assays were established and modified to analyze 97 pneumococcal serotypes.
Real-Time Polymerase Chain Reaction ; Serotyping ; Streptococcus pneumoniae/genetics* ; Serogroup

OBJECTIVE: To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL). METHODS: The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis. RESULTS: Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×10⁹/L, bone marrow involvement, high LDH, high β₂-MG levels, Ki-67≥50%, SOX11^-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis. CONCLUSION MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×10⁹/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.
Adult ; Humans ; Male ; Female ; Aged ; Middle Aged ; Lymphoma, Mantle-Cell/pathology* ; Hematopoietic Stem Cell Transplantation ; Retrospective Studies ; Ki-67 Antigen ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Transplantation, Autologous ; Prognosis

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations