Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Objective:To evaluate the left ventricular diastolic dyssynchrony (LVDD) and its influencing factors early after acute myocardial infarction (AMI) using phase analysis of SPECT gated myocardial perfusion imaging (GMPI).Methods:Bama miniature swines ( n=16) were subjected to establish AMI models. GMPI was performed before and 1 d after AMI to obtain the extent of myocardial perfusion defect (Extent, %) and left ventricular systolic dyssynchrony (LVSD)/LVDD parameters, namely the phase histogram bandwidth (PBW) and phase standard deviation (PSD). Meanwhile, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early to late peak mitral diastolic flow (E/A) were obtained by echocardiography. Independent-sample t test, paired t test and Pearson correlation analysis were used to analyze the data. Results:Sixteen AMI swines were successfully created. Compared to baseline, Extent, LVEDV and LVESV significantly increased on 1 d after AMI ( t values: -11.14, -4.55, -6.12, all P<0.001), while LVEF and E/A significantly decreased ( t values: 10.16, 2.18, P<0.001, P=0.046). GMPI showed that the LVDD parameters PBW and PSD increased significantly on 1 d after AMI when compared to those at baseline((142.25±72.06)° vs (33.06±8.98)°, (56.15±26.71)° vs (12.51±5.13)°; t values: -6.11, -6.60, both P<0.001). There were significant differences between LVSD parameters and LVDD parameters (PBW: (109.06±62.40)° vs (142.25±72.06)°, PSD: (44.40±25.61)° vs (56.15±26.71)°; t values: -2.73, -2.20, P values: 0.016, 0.044). LVDD parameters PBW, PSD were negatively correlated with E/A after AMI ( r values: -0.569, -0.566, P values: 0.021, 0.022), and positively correlated with the Extent ( r values: 0.717, 0.634, P values: 0.002, 0.008). The phase analysis of SPECT GMPI to evaluate LVDD showed good intra-observer and inter-observe reproducibility (intraclass correlation coefficient (ICC): 0.953-0.984, all P<0.001). Conclusions:LVDD occurs early on 1 d after AMI, and can reflect left ventricular diastolic dysfunction. The Extent is correlated with LVDD significantly. Phase analysis of SPECT GMPI is an accurate method to evaluate LVDD and left ventricular diastolic function.

Objective:To investigate the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT metabolic parameters for occult lymph node metastasis (OLM) in non-small cell lung cancer (NSCLC). Methods:A total of 183 patients (72 males, 111 females; age (61.5±8.4) years) who underwent 18F-FDG PET/CT and preoperatively diagnosed with clinical N0 stage (cN0) in Third Affiliated Hospital of Soochow University from January 2013 to December 2018 were retrospectively enrolled. All patients underwent anatomical pulmonary resection with systematic lymph node dissections within 3 weeks after 18F-FDG PET/CT examinations. According to the presence or absence of lymph node metastasis, patients were divided into OLM positive (OLM+ ) group and OLM negative (OLM-) group. Parameters of primary lesions, such as the maximum diameter (D max), tumor sites, morphological features, maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), metabolic total volume (MTV), total lesion glycolysis (TLG), tumor SUV max to liver SUV mean (TLR max), tumor TLG to liver SUV mean (TLR TLG) were analyzed. Mann-Whitney U test and χ2 test were used to compare the parameters between groups. Multivariable logistic regression was used to analyze the independent risk factors for OLM. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of different parameters. Results:Among 183 patients, 25 (13.7%, 25/183) of them were diagnosed as OLM. In OLM+ group, 46 lymph nodes were pathologically positive for metastasis, including 15 N1 disease and 31 N2 disease. D max (2.9(2.3, 3.7) vs 2.3(1.7, 2.8) cm), lobulation ((76.0%(19/25) vs 37.3%(59/158)), SUV max (11.1(7.9, 17.7) vs 4.7(2.3, 9.2)), TLG (41.5(10.2, 91.1) vs 15.6(6.5, 23.8) ml), TLR max (4.7(3.5, 7.6) vs 2.1(0.9, 4.0)) and TLR TLG (18.1(5.0, 44.3) vs 6.1(3.0, 11.4) ml) of the primary lesions in OLM+ group were significantly higher than those in OLM-group ( z values: from -4.709 to -3.247, χ2=13.190, all P<0.05). Multivariable logistic regression analysis showed that TLR max (odds ratio ( OR)=15.145, 95% CI: 3.381-67.830, P<0.001) and D max ( OR=3.220, 95% CI: 1.192-8.701, P=0.021) were independent risk factors for OLM. TLR max yielded the highest area under curve (AUC; AUC=0.794) with the threshold of 3.12, and the sensitivity, specificity, accuracy, positive predictive value and negative predictive value for predicting OLM were 92.0%(23/25), 63.3%(100/158), 67.2%(123/183), 28.4%(23/81) and 98.0%(100/102), respectively. Conclusions:TLR max of tumor is the independent risk factor for OLM in NSCLC patients. TLR max can sensitively predict OLM preoperatively in patients with NSCLC.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

OBJECTIVETo observe the effects of's neck acupuncture combined with swallowing rehabilitation on swallowing function and quality of life in patients with post-stroke pseudobulbar palsy.

METHODSOne hundred patients were randomly assigned in to an observation group and a control group, 50 cases in each one. The patients in the control group were treated with basic pharmaceutical treatment, including neurotrophy medication and free radical scavenging medication as well as swallowing rehabilitation; the patients in the observation group, on the basis of those in the control group, were treated with's neck acupuncture at Fengchi (GB 20), Yiming (EX-HN 14), Gongxue (Extra), Lianquan (CV 23), Wai Jinjin Yuye (Extra), Tunyan (Extra), Zhiqiang (Extra), Fayin (Extra), once a day, five times a week for continuous eight weeks. The Repetitive saliva-swallowing test (RSST), standardized swallowing assessment (SSA) and swallow quality-of-life questionnaire (SWAL-QOL) before and after treatment in the two groups were observed; the relationship between disease location and frequency and efficacy of's neck acupuncture was explored in the observation group.

RESULTSAfter treatment, the RSST, SSA and SWAL-QOL were superior to those before treatment (all<0.01), with more significant results in the observation group (all<0.01). The total effective rate was 91.7% (44/48) in the observation group, which was superior to 75.5% (37/49) in the control group (<0.01). The frequency of disease onset was one in 11 patients and 2 and above in 37 patients in the observation group, and the efficacy of one onset of disease was 100.0% (11/11), which was superior to two and above of onset 89.2% (33/37,<0.01). The number of patients with disease location at cortex and subcortex was 21, while that at capsula interna and basal ganglia was 27 in the observation group, the efficacy of two was similar (>0.05).

CONCLUSIONS 's neck acupuncture combined with swallowing rehabilitation could effectively improve dysphagia and quality of life in patients with post-stroke pseudobulbar palsy. No correlation of lesion locations on acupuncture efficacy is observed, while onset frequency is inversely proportional to efficacy.

Objective To investigate the effects of comprehensive pelvic floor rehabilitation program on pelvic floor muscle strength, female sexual function index (FSFI) score and sexual satisfaction scale for women (SSS-W) score in patients with perimenopausal female sexual dysfunction. Methods The clinical data of 120 patients with perimenopausal female sexual dysfunction were retrospectively analyzed, and all the patients were treated with estrogen and progesterone replacement therapy. Among the patients, 80 patients were treated with Kegel training program (control group), and 80 patients were treated with Kegel training program combined with comprehensive pelvic floor rehabilitation program (treatment group). The pelvic floor muscle strength, FSFI score, SSS-W score, incidence of algopareunia and sexual life frequency were compared between 2 groups. Results The pelvic floor muscle strength after treatment in treatment group was significantly better than that in control group. The Ⅲ,ⅣandⅤgrade of pelvic floor muscle strength in treatment group was in 5, 42 and 33 cases, and that in control group was in 21, 47 and 12 cases, and there was statistical difference (P<0.05). The FSFI scores and SSS-W scores after treatment in treatment group were significantly higher than those in control group:(32.24 ± 3.70) scores vs. (28.51 ± 2.95) scores and (139.80 ± 16.17) scores vs. (122.33 ± 13.75) scores, and there were statistical differences (P<0.05). The incidence of algopareunia after treatment in treatment group was significantly lower than that in control group:10.00%(8/80) vs. 55.00%(44/80), and there was statistical difference (P<0.05). The sexual life frequency after treatment in treatment group was significantly better than that in control group, the 0, 1, 2 and≥3 times/month of sexual life frequency in treatment group was in 0, 8, 20 and 52 cases, and that in control group was in 5, 34, 24 and 17 cases, and there was statistical difference (P<0.05). Conclusions Comprehensive pelvic floor rehabilitation program in patients with perimenopausal female sexual dysfunction can efficiently promote the recovery process of pelvic floor muscle strength, improve FSFI score and SSS-W score, and increase the degree of sexual satisfaction.

Objective To analyze the pathogenesis and prevention and treatment of limb deep venous thrombosis complicated by postoperative gynaecological malignant tumours.Methods A retrospective analysis of 22 cases with limb deep venous thrombosis complicated by postoperative gynaecological malignant tumours in our hospital were analyzed.According to the situation of patients,surgery or conservative treatment was conducted.The clinical efficacy after treatment was observed.Results In 22 cases,6 cases underwent surgical treatment,16 cases underwent conservative treatment.After treatment,18 cases were cured,3 cases were effective,1 case ineffective.After treatment,the TT,Pt,APTT and FBG levels were (24.17 ±2.13)s,(18.25 ±2.13)s,(31.68 ± 10.30)s and (2.26 ±0.52) g/L,which were all better than before treatment,the differences were statistically significant (t =10.362,9.774,12.281,8.462,P =0.028,0.032,0.012,0.029).Followed up for 3 months,no recurrence of LDVT was observed.Conclusion The cases of gynecological malignant tumor have higher risk of limb deep vein thrombosis,we should taken prevention actively,once diagnosed should take effective intervention measures to improve the prognosis.