Through combing and analysing the relevant records of Chongmai in The Inner Canon of the Yellow Emperor （《黄帝内经》）， the basis for the formation of the concept of Chongmai， its development， and the connotation of its name and reality are examined. It is believed that the concept of Chongmai is based on the observation of arterial pulsation by ancient people， and the practice of pulse diagnosis and blood letting by healing stone， to reflect the importance placed on the entity of the blood vessels， the concept of qi and blood in clinical practice. The name， route and function of Chongmai all reflect the above characteristics. With the development of medical theory and the standardization of the distribution and route of meridians by the three-Yin and three-Yang model thinking， the theory of the twelve meridians has taken a dominant position， and the arterial sites belonging to Chongmai are divided by the twelve meridians， resulting in the intersection and confusion between the positioning of the Chongmai and the twelve meridians in later generations. The independent function and disease characteristics of the Chongmai are becoming increasingly blurred， ultimately leading to a disconnection between the clinical application and theoretical positioning of Chongmai. Based on the high degree of belonging of the human arterial system to Chongmai， and based on the exuberance-decline and excess-deficiency， free and stasis of qi and blood， this article concluded that the connotation of Chongmai as the sea of blood， governs reproduction and menstruation， dominates disease of gynaecology， cold pathogen intruding the body， and mental disease， and formulates corresponding treatment methods， which has a unique value and significance in clinic.

Objective:To investigate the serum metabolites and their metabolic characteristics of patients with optic neuritis.Methods:Case-control study. From January 2021 to January 2022, 9 serum specimens of diagnosed patients with optic neuritis were collected in Department of Neurology from Beijing Tongren Hospital and 9 healthy subjects as the control. Among them, there were 5 females and 4 males in the optic neuritis group, aged (35.8±12.9) years; there were 5 females and 4 males in the healthy control group, aged (32.6±8.6) years. Liquid chromatography-mass spectrometry was used to detect metabolites in serum of healthy control and patients with optic neuritis. The principal component analysis (PCA) and orthogonal partial least-squares discriminination analysis (OPLS-DA) were used to analyze the differential metabolites . The variable importance projection value of OPLS-DA model and the P value of t-test was applied to find the different metabolites. Results:Thirty-seven metabolites were finally identified from serum samples. Four metabolites with variable important in projection (VIP) values larger than 1 and P values less than 0.05 were teased out, three metabolites, LysoPC (P-16∶0), LysoPC (16∶0), LysoPC (P-18∶0) belonge to phospholipid and one metabolite was L-Threonine, they were all down-regulated. The area under curve were 0.951, 0.889, 0.963 and 0.944, respectively. Conclusion:Based on metabonomic analysis, some metabolites in serum have changed, which can provide basis for biomarkers screening of optic neuritis.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

Objective:To assess the utility of whole-genome sequencing (WGS) in predicting Mycobacterium tuberculosis resistance to fluoroquinolones (FQs) and to establish a quantitative relationship between resistant gene mutations and resistance levels. Methods:A total of 296 drug-resistant tuberculosis surveillance strains with various resistance profiles, preserved by the National Tuberculosis Reference Laboratory of the Tuberculosis Prevention and Control Center at the Chinese Center for Disease Control and Prevention between 2013 and 2020, were included as study subjects. The Sensititre? MYCOTBI microplate method and WGS were used to assess the phenotypic and genotypic drug sensitivity of Mycobacterium tuberculosis to ofloxacin and moxifloxacin. Sensitivity, specificity, and concordance (Kappa value) of WGS in predicting fluoroquinolone sensitivity were calculated using phenotypic drug susceptibility testing (DST) results as the gold standard. A summary analysis was conducted on the distribution of drug resistance mutation sites and resistance levels. The paired χ 2 test was used to compare the detection rates between the two methods, with P<0.05 indicating statistical significance. Results:Among the 296 Mycobacterium tuberculosis strains with different resistance profiles, 196 were rifampicin-resistant, 50 were resistant to other drugs, and 50 were fully sensitive. WGS identified 81 strains carrying FQs resistance-related mutations, primarily at gyrA codons 94, 90, and 91. Sensitivity, specificity, and consistency (Kappa value) of WGS in predicting ofloxacin resistance were 86.5%, 98.1%, and 0.87, respectively. For moxifloxacin resistance prediction, these values were 80.0%, 99.5%, and 0.83, respectively. There was no statistically significant difference between the phenotypic DST and WGS detection rates for ofloxacin resistance (30.1% vs 27.4%, χ 2=3.06, P=0.08). However, the phenotypic DST detection rate for moxifloxacin resistance (33.8%, 100/296) was significantly higher than that of WGS (27.4%, 81/296) (χ 2=15.43, P<0.01). Analysis of the distribution of resistance mutation sites and resistance levels showed that different mutation sites corresponded to different minimum inhibitory concentrations (MICs). Multiple mutation combinations, including gyrA_D94G, gyrA_D94Y, and gyrA_D94N were mainly associated with high-level resistance, while gyrA_D94A, gyrA_A90V, and gyrA_S91P were primarily linked to low-level resistance. Conclusion:WGS demonstrates favorable sensitivity, specificity, and consistency in predicting FQs resistance and can partially predict resistance levels.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

Objective:To investigate the relationship between the levels of vascular endothelial growth factor (VEGF) and homocysteine (Hcy) in serum and diabetic retinopathy (DR) and diabetic nephropathy (DN).Methods:A total of 211 patients with type 2 diabetes mellitus (T2DM) who were treated in Beijing Tongren Hospital from February to July 2019 were selected as the case group, including 72 patients with T2DM (T2DM group), 45 patients with DR (DR group), 49 patients with DN (DN group), 45 patients with DR and DN (DR+DN group); 76 healthy people were selected as the control group. The levels of serum VEGF and Hcy were measured in all subjects. The course of diabetes, body mass index, waist to hip ratio, fasting blood glucose, glycosylated hemoglobin (HbA 1c), triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), urinary microalbumin/creatinine (ACR), urinary immunoglobulin G/creatinine (IGU/CR), urinary transferrin/creatinine (TRU/CR), urinary α1-microglobulin/creatinine (α1/CR), serum urea nitrogen, serum creatinine, hypersensitive C-reactive protein (hCRP) and erythrocyte sedimentation rate (ESR) were also observed in the case group. Results:The VEGF level of the T2DM group, DR group, DN group and DR+DN group was 90.02(61.24, 118.52), 124.38(81.50, 170.28), 133.19(78.84, 168.49), 124.08(79.82, 187.33)ng/ml respectively, which were significantly higher than that of the control group 50.31(21.10,67.74)ng/ml(all P<0.05); Compared with the T2DM group, the VEGF level in the DR group, DN group and DR+DN group increased significantly (all P<0.05). The level of Hcy in the DN group and DR+DN group [(12.58±3.66), (11.91±2.42) μmol/L, respectively] was higher than that in the control group [(10.44±2.09) μ mol/L], and the difference was statistically significant ( P<0.05). There was no statistically significant difference in VEGF and Hcy levels in different stages of DR ( U=264.00, t=-0.43, P>0.05). The Hcy level of DN patients in the group of massive proteinuria was higher than that in the group of microalbuminuria [(15.00±1.87) vs (11.79±3.76) μmol/L, t=-2.82, P=0.01].VEGF was positively correlated with ACR, TRU/CR and IGU/CR ( r=0.23, 0.19, 0.17, all P<0.05),while Hcy was positively correlated with serum urea nitrogen, serum creatinine, ACR, TRU/CR, IGU/CR and α 1/CR ( r=0.35, 0.44, 0.22, 0.19, 0.21, 0.29, all P<0.05). Conclusions:The level of VEGF in the serum of DR and DN patients increased, suggesting that VEGF may play a role in the development of DR and DN, but there was no significant difference in the level of VEGF in patients with different stages of DR and different urinary albumin excretion rate of DN.The level of serum Hcy in DN patients increased, and that was higher in massive proteinuria group, suggesting that serum Hcy may have clinical significance in the diagnosis and monitoring of DN.

Objective:To understand the HIV antibody screening results among the preoperative examination patients in Beijing Tongren Hospital from 2008 to 2018.Methods:A retrospective analysis of the HIV antibody screening data of thepreoperative examination patients from 2008 to 2018 in Beijing Tongren Hospital was performed with software SPSS19.0. Trend chi-square was used to analyze the positive rate, age, marital status, household registration and so on.Results:Among the 750 013 clinical patients, 428 (0.057%) cases were screened anti-HIV positive and 370(0.049%) cases were confirmed anti-HIV positive when detected with western blotting.Most of the HIV-infectedindividuals were non-Beijing nationality, accounting for 60.27%.Among the 370 HIV-infected patients, there were 334 males (90.27%) and 36 females (9.73%). The age was distributed mainly between 20-40 years old (62.43%), secondly between 40-60 years old (28.65%).361 (97.57%)HIV-infected cases were transmitted by the sex and the MSM men increased from 2008 to 2018 (trend χ2=7.307, P=0.007). There were 22 cases (5.95%) with HBsAg positive, 11 cases (2.97%) with anti-HCV positive. Among the 159 HIV-positive patients (42.97%) companied with syphilis specific antibody positive, there were 64 cases (17.30%) with TRUST tests positive. Additionally, 178 (48.11%) HIV-infected patientsfirst visited doctors because of ocular disease in the hospital; secondly, 71 (19.19%) HIV-infected patientsfirst visited the dermatology. Conclusions:The number of HIV-infected patientsmarkedly increased from 2008 to 2018. The sexual transmission is still the main pathway for HIV infection, particularly homosexual transmission. Moreover, the results indicate that it is necessary to detect HIV antibody for the ocular disease patients.

Objective:To understand the HIV antibody screening results among the preoperative examination patients in Beijing Tongren Hospital from 2008 to 2018.Methods:A retrospective analysis of the HIV antibody screening data of thepreoperative examination patients from 2008 to 2018 in Beijing Tongren Hospital was performed with software SPSS19.0. Trend chi-square was used to analyze the positive rate, age, marital status, household registration and so on.Results:Among the 750 013 clinical patients, 428 (0.057%) cases were screened anti-HIV positive and 370(0.049%) cases were confirmed anti-HIV positive when detected with western blotting.Most of the HIV-infectedindividuals were non-Beijing nationality, accounting for 60.27%.Among the 370 HIV-infected patients, there were 334 males (90.27%) and 36 females (9.73%). The age was distributed mainly between 20-40 years old (62.43%), secondly between 40-60 years old (28.65%).361 (97.57%)HIV-infected cases were transmitted by the sex and the MSM men increased from 2008 to 2018 (trend χ2=7.307, P=0.007). There were 22 cases (5.95%) with HBsAg positive, 11 cases (2.97%) with anti-HCV positive. Among the 159 HIV-positive patients (42.97%) companied with syphilis specific antibody positive, there were 64 cases (17.30%) with TRUST tests positive. Additionally, 178 (48.11%) HIV-infected patientsfirst visited doctors because of ocular disease in the hospital; secondly, 71 (19.19%) HIV-infected patientsfirst visited the dermatology. Conclusions:The number of HIV-infected patientsmarkedly increased from 2008 to 2018. The sexual transmission is still the main pathway for HIV infection, particularly homosexual transmission. Moreover, the results indicate that it is necessary to detect HIV antibody for the ocular disease patients.

Objective: To evaluate the consistency between prostate biopsy and postoperative pathological grade, analyze the influencing factors that may lead to upgrade or downgrade, and to establish a prediction model. Methods: The clinical data of biopsy GS3+ 3=6(GR1, 330 cases) and GS3+ 4=7(GR2, 340 cases) patients from January 2013 to December 2018 in the first affiliated hospital, College of Medicine of Zhejiang university were retrospectively analyzed. The median age was 67 years old(ranging 35 to 100 years old). The median BMI was 23.74 kg/m²(ranging 16.22-38.74 kg/m²). The Median tPSA was 10.266 ng/ml(ranging 0.017-147.575 ng/ml). The median prostate volume was 29.43 ml(5.92-187.20 ml). The median PSAD was 0.34 (ranging 0.01-4.02). The median percentage of positive puncture cores was 0.25 (ranging 0.08-1.00). There were 161 patients in clinical stage ≤T_1c, 344 patients in T_2a-T_2c and 165 patients in clinical stage ≥T₃. 670 cases all accepted the radical prostatectomy. Consistency of prostate biopsy and radical prostatectomy Gleason grade was recorded. If the postoperative Gleason grade was higher than that in biopsy, it was defined as upgrade. Otherwise, it was defined as downgrade. Multivariate logistic regression model was used to evaluate the influencing factors leading to upgrades in GR1 patients or downgrades in GR2 patients. Nomograms were drawn based on the models with AUC and Horsmer-Lemeshaw test conducted to test the discrimination and calibration of the models. Results: Among the 670 patients included, 165 cases (50.0% of GR1) upgrades and 27 cases (7.9% of GR2) downgrades. PSAD≥0.25(OR=3.015) and clinical stage≥T_2b(OR=7.185)were independent influencing factors for the upgrade in GR1 patients, while PSAD<0.15(OR=4.208) and clinical stage≤T_1c(OR=4.530) were independent influencing factors for downgrade. The nomograms were drawn with the above variables. The AUC of the model (0.781 for GR1 group, 0.741 for GR2 group) and the hosmer-remeshaw test results (P=0.993 for GR1 group, P=0.234 for GR2 group) show that the nomograms have good discrimination and calibration. Conclusions PSAD and clinical stage are independent influencing factors for the upgrade or downgrade. Nomograms may provide help for clinicians to judge the accuracy of prostate biopsy. However, the nomograms still needs to be verified in clinical practice