This study was aimed at understanding the trends in,and scope of,severe fever with thrombocytopenia syndrome(SFTS)in Nanjing,analyzing the spatial distribution pattern,detecting high incidence cluster areas and key popula-tions,and scientifically guiding prevention and control strategies and measures.We obtained data on SFTS cases from 2010 to 2023 in Nanjing from the China Disease Control and Prevention Information System,and described the time,popu-lation,and spatial distribution characteristics.We used joinpoint regression to calculate the annual percentage change(APC)in incidence,then used FleXScan spatial clustering scan analysis to explore spatial clustering areas at the street level.A total of 507 SFTS cases were reported from 2010 to 2023 in Nanjing.The APC was 31.8％(95％CI:22.5％-41.9％,P＜0.001),and the reported incidence in 2023 was 1.42/100 000(134 cases).The seasonal indices from May to August were 2.7,2.1,3.0,and 1.3,respectively,accounting for 76.1％of the total cases.The median age was 66(IQR:55,73)years,which gradually increased from 59 years in 2010-2011 to 68 in 2022-2023(P＜0.001);94.1％of cases were in individuals 45 years or older.Farmers,homemakers/unemployed individuals,and retirees accounted for 90.1％.The epidemic area increased from 11 streets in four districts in 2010-2011 to 58 streets in 11 dis-tricts in 2022-2023.Except for 2012-2013,global spatial autocorrelation analysis showed positive Moran's I values(0.224-0.526,P＜0.001),and FlexScan scan indicated that several streets in Lishui District and Jiangning District were the most likely clusters.Four streets in Pukou District were the secondary clusters from 2018 to 2023,and three streets in Luhe District in 2022-2023 were the secondary clusters(all P＜0.05).The reported incidence of SFTS in Nanjing showed a rapid upward trend,with spread of epidemic areas.The spatial distribution pattern was clustered.Strengthened training in diagnosis and treatment technology and detection ability of medical institutions,surveillance in high-incidence areas,tracing of case flow,and health education of tick and disease prevention knowledge are recommended.

Objective To standardize the management of clinical trials in our hospital,reduce the incidence of protocol deviations,and provide a reference for improving the quality of clinical trials.Methods The healthcare failure mode and effect analysis(HFMEA)method was used to determine the potential failure modes of the current protocol deviation.The frequency,severity and detectability of failure modes were quantified and evaluated.The risk priority number(RPN)was calculated and the corresponding improvement measures were proposed.The RPN values before and after the implementation of HFMEA were statistically analyzed to evaluate the improvement effect.Results After the implementation of HFMEA activities,the RPN values of 14 potential failure modes decreased significantly(P<0.05);The risk level of 12 potential failure modes decreased.The HFMEA team members'ability in finding and solving problems,communication and cooperation were significantly improved.Conclusions The implementation of HFMEA activities contributes to the management of protocol deviation in clinical trials,can effectively reduce the occurrence of protocol deviation,and provides experience for improving the quality of drug clinical trials.

The lingnan liver-soothing and spirit-regulating acupuncture and moxibustion technique,developed by Professor FU Wen-Bin,a renowned traditional Chinese medicine expert in Guangdong Province,represents an innovative achievement in acupuncture therapy for depression-related disorders.Drawing upon the rich legacy of master scholars,meticulous study of medical literature,and over three decades of continuous research and innovation,Professor FU has formulated this technique with profound influence and widespread application.By tracing the developmental trajectory of the Lingnan liver-soothing and spirit-regulating technique,this paper sheds light on its significant guiding principles and reference value for the development of other distinctive acupuncture techniques.Furthermore,it offers insights and inspiration for advancement in various fields of traditional Chinese medicine.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/ β-catenin signaling pathway via targeting PTP1B.

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q₁, Q₃) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q₁, Q₃) of 42 (20, 55) and the median exposure period (Q₁, Q₃) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
Male ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology* ; Incidence ; Family Characteristics

Objective:To evaluate the effectiveness of esketamine during perioperative anesthesia for acute and chronic pain after cesarean section.Methods:One hundred and fifty patients scheduled for elective cesarean section under spinal anesthesia were randomly assigned into 2 equal groups ( n=75) using a random number table: esketamine group (group E) and control group (group C). Subarachnoid block was administered with 9-11 mg of hyperbaric bupivacaine with 0.33% glucose concentration. After the delivery of the fetus, 0.15 mg/kg (1 mg/ml) esketamine was pumped intravenously for 30 min in the group E, while the same dosage of normal saline was administered in the group C. Furthermore, patients received an intravenous patient controlled intravenous analgesia (PCIA) pump after surgery (100 μg sufentanil + 1.25 mg/kg esketamine + 8 mg ondansetron for the group E, 100 μg sufentanil + 8 mg ondansetron for the group C). Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded in the initial time of esketamine administration, and 5, 15 min, and 30 min after administration. The pain Numerical Rating Scale (NRS) score at rest and during coughing were recorded at 2, 6, 12, 24 h and 48 h after surgery. The first analgesic time and cumulative sufentanil consumption were recorded at 0-12 h, 12-24 h, 24-48 h, 0-24 h and 0-48 h after surgery. Moreover, we recorded the incidence of chronic pain at 3 and 6 months after surgery. Results:There were no significant differences in HR, SBP and DBP between the two groups immediately after administration of esketamine and 5, 15 min and 30 min after administration (all P>0.05). At rest or during coughing, the pain NRS score were significantly lower at 2, 6 h, and 12 h postoperatively in group E compared to group C (all P<0.05). The time to first analgesia in group E was significantly longer than the group C [(176.8±18.3)min vs (148.5±16.9)min, P<0.05]. The cumulative sufentanil consumption was significantly lower in group E during 0-12 h, 12-24 h, 0-24 h and 0-48 h postoperatively than in group C (all P<0.05), but there was no statistical significance between the two groups at 24-48 h ( P>0.05). There were no significant difference between the two groups in the incidence of chronic pain at 3 months and 6 months after surgery ( all P>0.05). The incidence of chronic pain in group E was lower than that in group C at 3 months [13.4%(9/67) vs 18.8%(13/69), P=0.392] and 6 months [10.7%(6/56) vs 16.1%(10/62), P=0.391], but the difference was not statistically significant. Conclusions:Perioperative administration of esketamine provided superior short-term analgesia after cesarean section and did not increase the psychotomimetic adverse event rate. However, the development of chronic pain was not restrained.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of moxifloxacin in Chinese healthy adult subjects.Methods A single-center,randomized,open,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of moxifloxacin tablets 0.4 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of moxifloxacin in plasma were determined by liquid chromatography-tandem mass spectrometry.Results The main pharmacokinetic parameters of moxifloxacin in fasting state and high-fat diet states were as follows:Cmax were(2 286.09±802.64)and(1 963.33±474.99)ng·mL-1;t1/2 were(12.32±1.42)and(13.56±1.38)h;AUC0-twere(2.70±0.51)×104 and(2.60±0.55)×104 ng·mL-1·h;AUC0-∞ were(2.88±0.54)×104 and(2.85±0.63)×104 ng·mL-1·h;tmax were 1.50 and 2.00 h.After high-fat diet,the AUC was not significantly changed,Cmax was decreased by 14.12％,and tmax was indistinctively delayed(all P＞0.05).Conclusion Food had no effects on the absorption rate and degree of moxifloxacin.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).