Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To investigate the relationship between perioperative nutritional risk and venous thromboembolism(VTE)in patients with hip fracture.Methods A total of 379 patients with unilateral hip fracture due to fall or sprain who underwent elective surgery were selected and divided into the non-VTE group(246 cases)and the VTE group(133 cases)according to whether or not VTE occurred during perioperative period.Basic information,surgical and anesthesia records,nutritional risk related indicators,inflammatory indicators and outcome indicators of patients were collected.Multiple Logistic regression was used to analyze the independent influencing factors of perioperative VTE.Receiver operating characteristics(ROC)curves were used to assess the ability to discriminate independent factors,and DeLong test was used to compare area under the curve(AUC).Results Compared with the non-VTE group,the proportion of patients in the VTE group was older,complicated with hypertension,the time to visit hospital more than 2 days,received(hollow/intramedullary nail)internal fixation,perioperative blood transfusion,ASA gradeⅢtoⅣ,and higher nutritional risk screening Table(NRS)-2002 scores on admission and higher postoperative neutrophil/lymphocyte ratio(NLR).Nutritional prognosis index(PNI),hemoglobin(Hb)and prealbumin(PA)at admission and after operation were lower in the VTE group than those in the non-VTE group(P＜0.01).Multivariate Logistic regression analysis showed that PNI was decreased,NRS-2002 scores and PA were increased,and the time of visit hospital was>2 days after internal fixation.American College of Anesthesiologists(ASA)gradesⅢ-Ⅳwere independent risk factors for perioperative VTE of hip fracture(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of NRS-2002 at admission was 0.739(0.692-0.783),and that of PNI at admission was 0.720(0.672-0.765),both of which were better than other influencing factors(P＜0.01).Conclusion NRS-2002 and PNI are good predictors of perioperative VTE in patients with hip fracture.

Objective:To investigate the effects of preoperative pre-rehabilitation on early functional recovery after knee arthroplasty under the multidisciplinary collaboration mode of accelerated rehabilitation surgery.Methods:The clinical data of 51 patients who underwent total knee arthroplasty in the Department of Orthopedics, Jinjiang Hospital from September 2019 to December 2021 were retrospectively analyzed. These patients were divided into an observation group ( n = 24) and a control group ( n = 27). The observation group received pre-rehabilitation before knee replacement surgery, while the control group did not. After completing the admission procedures, patients in the observation group underwent rehabilitation evaluation in the rehabilitation clinic and received individualized rehabilitation training. The control group did not undergo preoperative pre-rehabilitation but underwent the same individualized rehabilitation training as the observation group. The rehabilitation specialist evaluated the patients' rehabilitation scores [hospital for special surgery knee (HSS) score, visual analog scale (VAS) score] at 2 and 5 days after surgery. The main outcome measures included the range of motion (ROM) of the patient's knee joint at 2 and 5 days after surgery, HSS score at 2 and 5 days after surgery, VAS score at 5 days after surgery, the number of days from surgery to discharge, the incidence of postoperative complications, and the rate of outpatient visits after surgery. Results:There was no significant difference in postoperative ROM of the knee joint between the observation and control groups at 2 days after surgery ( P > 0.05). However, there was a significant difference in score of ROM of the knee joint at 5 days after surgery between the two groups [(100.08 ± 7.75) points vs. (88.44 ± 16.09) points, t = 3.34, P = 0.002]. There was no significant difference in HSS score between the two groups at 2 days after surgery ( P > 0.05). However, there was a significant difference in HSS score between the two groups at 5 days after surgery [(62.84 ± 5.78) points vs. (57.09 ± 6.53) points, t = 3.31, P = 0.002]. There was a significant difference in VAS score (exercise) between the two groups at 5 days after surgery [(3.42 ± 1.02) points vs. (5.37 ± 1.15) points, t = -6.39, P < 0.001]. There was no significant difference in the number of days from surgery to discharge between the two groups ( P > 0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P > 0.05). However, there was a significant difference in the rate of outpatient visits between the two groups [7/17 vs. 1/26, χ2 = 4.45, P = 0.035]. Conclusion:Preoperative pre-rehabilitation in the accelerated rehabilitation surgery model under multidisciplinary collaboration can help improve the early function of patients undergoing total knee arthroplasty, reduce the pain of postoperative rehabilitation, improve the postoperative rehabilitation compliance, and ultimately enhance patient satisfaction with the surgery.

OBJECTIVE: To compare the clinical effect of conventional acupuncture combined with pricking and cupping at Jianbo area and conventional acupuncture in the treatment of scapulohumeral periarthritis of frozen stage. METHODS: A total of 66 patients with scapulohumeral periarthritis of frozen stage were randomly divided into a combination group (31 cases) and an acupuncture group (35 cases, 1 case dropped off). Both groups were given functional exercise. Patients in the acupuncture group were treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14) and ashi point on the affected side, once every other day, three times a week, for a total of 4 weeks. On the basis of treatment in the acupuncture group, the patients in the combination group were treated with pricking and cupping at Jianbo area (the area surrounded by the 3 acupoints of Tianzong [SI 11], Naoshu [SI 10] and Jianzhen [SI 9]), once a week for 4 weeks. The University of California-Los Angeles (UCLA) shoulder joint score, visual analogue scale (VAS) score before treatment, after treatment and after 6 months of treatment completion (follow-up) and tenderness threshold before and after treatment, and the clinical effects of the two groups after treatment and in follow-up were evaluated. RESULTS: In the two groups, after treatment and in follow-up, the UCLA shoulder joint scores were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). In the combination group, after treatment and in follow-up, the UCLA shoulder joint score was higher than that of the acupuncture group (P<0.05), and the VAS score was lower than that of the acupuncture group (P<0.05). After treatment, the tenderness thresholds of the two groups were higher than those before treatment (P<0.05), and the tenderness threshold in the combination group was higher than that in the acupuncture group (P<0.05). After treatment and in follow-up, the cured and markedly effective rate of the combination group was 48.4% (15/31) and 51.6% (16/31) respectively, which was higher than 23.5% (8/34) and 23.5% (8/34) of the acupuncture group (P<0.05). CONCLUSION Pricking and cupping in Jianbo area combined with conventional acupuncture can improve shoulder joint function and relieve shoulder joint pain in patients with scapulohumeral periarthritis of frozen stage, and the curative effect is better than that of single conventional acupuncture.
Humans ; Periarthritis/therapy* ; Acupuncture Therapy ; Shoulder Pain/therapy* ; Shoulder Joint ; Acupuncture Points ; Treatment Outcome

OBJECTIVE: Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19). METHODS: This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis. RESULTS: Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals. CONCLUSION Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.
Humans ; Adult ; Middle Aged ; Aged ; COVID-19/epidemiology* ; SARS-CoV-2 ; Case-Control Studies ; China/epidemiology* ; Tea

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.
Humans ; Tandem Mass Spectrometry/methods* ; Irritable Bowel Syndrome/drug therapy* ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Glycosides ; Chromatography, High Pressure Liquid/methods*

DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins. Mechanistically, shikonin inhibited the activation of ataxia telangiectasia mutated (ATM), and to a lesser degree ATM and RAD3-related (ATR), two master upstream regulators of the DDR signal, through inducing degradation of ATM and ATR-interacting protein (ATRIP), an obligate associating protein of ATR, respectively. As a result of DDR inhibition, shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models. While degradation of ATRIP is proteasome dependent, that of ATM depends on caspase- and lysosome-, but not proteasome. Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs. These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin. Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

Objective To determine the epidemiological characteristics of measles in Jinshan District of Shanghai in 2002‒2019. Methods This study was a secondary data analysis using measles surveillance system and epidemiological case reports in Jinshan District from January 2002 through December 2019. Temporal characteristics of the disease onset was determined by a concentration method. ArcGis 10.4 and SaTScan 9.6 software were used for spatiotemporal clustering scanning analysis. Results From 2002 through 2019， a total of 289 cases of measles were reported in Jinshan District， Shanghai， with an average annual incidence of 2.24 per 10⁵. The annual incidence fluctuated from 0 to 11.27 per 10⁵. The highest incidence was recorded in 2005 （11.27 per 10⁵）， followed by a decline； however， there was a rebound in 2008 （5.26 per 10⁵） and 2015 （3.30 per 10⁵）. The concentration M was determined to be 0.62， showing a clear seasonality concentrated in February to May. The spatiotemporal scan found that spatial and temporal clusters were more likely to occur in the areas with higher population density such as Zhujing Town and Shihua Community and between 2002 and 2009. The majority of measles cases were infants and children under the age of 1 and adults aged 20‒39 years. Approximately 66.78% of measles cases reported unknown vaccination history. In addition， in children aged 8 month to 4 years， the vaccination rate of measles-containing vaccines in the domestic migrants was much lower than the local residents （χ²=4.44， P=0.035）. Conclusion The incidence of measles in Jinshan District presents a downward trend. The population affected has a "two-way displacement"， which is concentrated in the more populated areas. It is necessary to strengthen measles surveillance and implement supplementary immunization programs with measles-containing vaccines for at-risk populations.

Objective To evaluate the vaccination of live attenuated varicella vaccine ((VarV) in Jinshan District of Shanghai. Methods Descriptive and analytical epidemiological analysis was carried out using the information of VarV immunization of children born between November 1, 2006 and October 31, 2018 (1-12 years) in the Jinshan District Immunization Program Information System. Results There were 82 584 registered children aged 1-12 years in Jinshan District, and the vaccination rate of VarV at the first dose (VarV1) was 90.95%. The vaccination rate of children in this city was higher than that of migrant children, and the annual vaccination rate of children born in different years was between 59.81% and 99.93%. The vaccination rates in northern, central and southern Jinshan District were 89.25%, 93.27% and 91.39%, respectively. Among the 82 584 registered children, the second dose of VarV (VarV2) vaccination rate was 49.01%. The vaccination rate of children in this city was higher than that of migrant children, and the annual vaccination rate of children born in different years was between 25.94% and 77.14%. The vaccination rates in northern, central and southern Jinshan District were 28.72%, 45.88% and 66.30%, respectively. Conclusion The VarV1 vaccination rate of children aged 1-12 in Jinshan District was higher, but the VarV2 vaccination rate was relatively low. It is necessary to further strengthen publicity in key areas to improve the level of VarV2 vaccination.

BACKGROUND:In perioperative period of total knee replacement in elderly patients, it is crucial to maintain the normal function of blood coagulation. However, many factors may influence coagulation function of patients in perioperative period. Of them, anesthesia is an important factor. Different anesthesia methods wil produce different effects on blood coagulation. Appropriate anesthesia methods should be selected in the clinic to maintain the stability of coagulation function. OBJECTIVE:To explore the effect of application of general anesthesia and epidural anesthesia in elderly knee replacement and the effects on the function of blood coagulation. METHODS:A retrospective analysis was performed on clinical data of 135 elderly patients after total knee replacement in Dongying Hospital of Shandong Provincial Hospital Group from September 2012 to September 2013. Al patients were divided into control group (67 cases;general anesthesia) and observation group (68 cases;epidural anesthesia) according to the mode of anesthesia. Coagulation indexes and D-dimer levels were observed before anesthesia, 6 hours after anesthesia, and 1 day after replacement in both groups. The incidence of deep venous thrombosis was measured and compared between the two groups in 12-month fol ow-up.
RESULTS AND CONCLUSION:Through the statistics and comparison, no significant difference was detected in blood coagulation indexes at different time points in the two groups (al P>0.05). However, significant differences in D-dimer levels were detectable between the two groups at 6 hours after anesthesia and in the morning at 1 day after replacement. D-dimer levels were significantly lower in the observation group than in the control group (al P<0.05). The incidences of deep venous thrombosis were 3%and 21%in the observation and control groups, respectively, showing significant differences (P<0.05). These results suggest that epidural anesthesia during elderly totak knee replacement obtained good effects, and could maintain stable coagulation function.