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γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
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Humans , Receptors, Antigen, T-Cell, gamma-delta , Immunotherapy, Adoptive , T-Lymphocytes , Immunotherapy , Neoplasms/therapyABSTRACT
ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.
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Objective:To investigate the safety and feasibility of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy(VATS) for esophageal cancer and Siewert type I esophago-gastric junction carcinoma.Methods:The patients with middle-lower segment esophageal cancer or Siewert type I esophago-gastric junction carcinoma received minimally invasive esophagectomy between October 2020 and June 2021, and the clinical data was collected and analyzed.Results:26 patients received Ivor-Lewis procedure underwent uniportal VATS, while 45 patients underwent McKeown surgery under multiport VATS. The average operation time of patients in the two groups were(265±110)min and (235±94)min, and the average intraoperative blood loss were(80±57)ml and(105±60)ml. The mean number of lymph nodes removed in the surgery were (19.3±2.9) and 18.6±2.7 respectively in two groups, and the mean length of hospital stay was(7.5±3.5)days and(8.3±2.7)days. The incidence of perioperative complications were not significantly different in two groups. The VAS score of patients received Ivor-Lewis procedure underwent uniportal VATS was lower than that of patients received McKeown surgery in ostoperative day 1, day 3, day 7 and 1 month. The difference was statistically significant in two groups( P<0.05). Conclusion:The Ivor-Lewis procedure under uniportal VATS for esophageal cancer and Siewert type I esophago-gastric junction carcinoma has the advantage of less postoperative pain, and the procedure is feasible in clinical practice.
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Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.
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Objective:To study the clinical characteristics and management strategies of late bleeding after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients with post-pancreaticoduodenectomy hemorrhage (PPH) admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from March 2018 to March 2022 were retrospectively analyzed, including 42 males and 16 females, aged (61.88±11.02) years old. According to the occurrence of intra-abdominal erosion factors (e.g., pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, intra-abdominal abscess), patients were divided into the erosion group ( n=42) and non-erosion group ( n=16). All patients underwent standard lymphadenectomy. Clinical data including the PPH time-point, occurrence of rebleeding, and treatment outcomes were accessed. The management strategies of PPH in the two groups of patients were analyzed. Results:The PPH time-point in the erosion group and non-erosion patients was 8.00 (5.00, 19.25) d and 21.50 (12.75, 26.75) d, respectively ( P=0.001). PPH can occurred within one month after surgery in both erosion and non-erosion groups. In the erosion group, 31 cases (73.81%, 31/42) were treated by re-operation, two (4.76%, 2/42) by interventional radiology and nine (21.43%, 9/42) with conservative protocol, respectively. In the non-erosion group, five cases (31.25%, 5/16) were treated by re-operation, seven (43.75%, 7/16) by interventional radiology and four (25.00%, 4/16) with conservative protocol, respectively. The incidence of re-bleeding is higher in the erosion group [47.6% (20/42) vs 12.5% (2/16), P<0.05]. Clinical manifestations, sites and severity of bleeding, and treatment outcomes were also different in the erosion and non-erosion groups (all P<0.05). Conclusions:The occurrence of intra-abdominal erosion factors can affect the clinical characteristics and treatment strategy of late bleeding after laparoscopic pancreaticoduodenectomy. Surgery remains the treatment of choice for post-pancreaticoduodenectomy hemorrhage either as an urgent or last resort.
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The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.
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Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.
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Objective To investigate the prevalence of Echinococcus infection in small mammals in Shiqu County, Sichuan Province from 2015 to 2020, so as to provide insights into echinococcosis control in Shiqu County. Methods One setting with frequent activity of small mammals was sampled as the survey site from each of 9 townships where human alveolar echinococcosis was hyperendemic, in Shiqu County, Sichuan Province from 2015 to 2020. Two quadrats measuring 50 m × 50 m were assigned in each survey site during the period between July and August from 2015 to 2020 to capture all small mammals in quadrats, and the species of small mammals were identified by morphological characteristics. All captured small mammals were dissected in the field and Echinococcus infection was identified by visual examinations. The affected organs of Echinococcus-infected small mammals were collected, and Echinococcus infection was detected using PCR assay, with Echinococcus species characterized. The prevalence of Echinococcus infection was calculated in small mammals, and the trends in the prevalence of Echinococcus infection were analyzed during the period from 2015 to 2020. In addition, the prevalence of Echinococcus infection was compared in small mammals using visual examinations and PCR assay. Results A total of 2 692 small mammals were captured in the survey sites of Shiqu County from 2015 to 2020, and morphology characterized 1 360 Microtus fuscus (50.52%) and 1 332 Plateau pika (49.48%). The prevalence rates of Echinococcus infection were 35.63%, 19.16%, 21.41%, 8.40%, 7.68% and 4.44% by visual examinations and 18.96%, 5.36%, 5.61%, 4.58%, 3.30% and 0.37% by PCR assay in small mammals in Shiqu County from 2015 to 2020, both showing a tendency towards a decline year by year (χ2 = 215.024 and 117.045, both P values < 0.001). The prevalence of Echinococcus infection was significantly higher in small mammals by visual examinations than by PCR assay during the period from 2015 to 2020 except in 2018 (χ2= 33.597, 21.815, 51.373, 17.268 and 9.537, all P values < 0.01). PCR assay detected a reduction in the prevalence of E. multilocularis infection from 10.21% to 0.37% and a reduction in the prevalence of E. shiquicus infection from 8.75% to 0 in small mammals in Shiqu County from 2015 to 2020, both appearing a tendency towards a decline year by year (χ2 = 117.045 and 43.436, both P values < 0.001). In addition, the prevalence of E. multilocularis and E. shiquicus infections reduced from 15.19% to 0.45% and from 8.23% to 0 in M. fuscus, and the prevalence of E. multilocularis and E. shiquicus infections reduced from 7.76% to 0 and from 9.01% to 0 in P. pika in Shiqu County from 2015 to 2020. Conclusions M. fuscus and P. pika were dominant species of small mammals in Shiqu County, Sichuan Province from 2015 to 2020, and E. multilocularis infection was mainly found in M. fuscus and E. shiquicus infection mainly found in P. pika. The prevalence of Echinococcus infection appeared a tendency towards a decline in both M. fuscus and P. pika year by year during the period from 2015 to 2020.
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The latest guideline about ulcerative colitis (UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall (mechanical barrier) injury with the imbalance between intestinal epithelial cells (IECs) regeneration and death, as well as tight junction (TJ) dysfunction. It is suggested that biological barrier (gut microbiota), chemical barrier (mucus protein layer, MUC) and immune barrier (immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This study aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.
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Rats , Animals , Colitis, Ulcerative/metabolism , Moxibustion , Rats, Sprague-Dawley , Acupuncture Therapy , AcupunctureABSTRACT
Objective To summarize the clinical characteristics of patients with occupational melanosis. Methods Diagnostic data of 69 patients with occupational melanosis was analyzed using retrospective analysis. Results The main occupational hazards for the 69 patients with occupational melanosis were coal tar, petroleum and its fractionated products, pigments and dyes and their intermediates, rubber additives and rubber products. The median length of occupational exposure and disease latency were 8.0 and 6.0 years, respectively, with a highly positive correlation between them (Spearman correlation coefficients=0.962, P<0.01). Skin lesions were mainly found on exposed areas such as the face-to-neck and limbs, prevalence of 94.2% and 75.4% respectively. And 78.3% of patients had skin lesion on more than two sites. The lesions were mostly in the form of irregular flakes (59.4%), with a gray-black color (44.9%). About 43.5% of patients experienced skin itching. Complete blood count, liver function, and kidney function were all within normal ranges. Skin biopsy results showed that epidermal hyperkeratosis, thinning of the spinous layer, liquefaction degeneration of basal cells, increased superficial dermal melanocytes, and infiltration of lymphocytes, histiocytes, and melanocytes around the blood vessels. Reflectance confocal microscopy (RCM) detection showed focal liquefaction degeneration of basal cells in the lesions, with a significant infiltration of melanocytes and inflammatory cells in the dermal papillae and superficial layers. Conclusion The primary target organ of occupational melanocytes is the skin, and no damage to other organs was identified thus far. Results from skin biopsies and RCM examinations can be used for differential diagnosis.
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Objective To investigate the clinical efficacy and safety of fruquintinib combined with sintilimab in the treatment of advanced microsatellite stable (MSS) colorectal cancer. Methods A retrospective study of 44 patients with MSS colorectal cancer treated with fruquintinib and sintilimab was conducted.The patients were divided into the fruquintinib alone (n=22) and fruquintinib combined with sintilimab (n=22) groups.The treatment regimen was as follows: The patients in the fruquintinib alone group consumed oral fruquintinib capsules at 5 mg/d once for three consecutive weeks with a one week stop in 28 day cycles.The patients in the fruquintinib combined sintilimab group were injected intravenously with sintilimab (200 mg) once per three weeks, and fruquintinib was used in the same manner as the fruquintinib alone group. Results The objective response rate (ORR) of the fruquintinib alone group was 9.09%, the disease control rate (DCR) of the fruquintinib alone group was 45.45%.The ORR of the fruquintinib combined with sintilimab group was 18.18%, and the DCR was 63.64%.The median PFS of the fruquintinib alone and fruquintinib combined with sintilimab groups were 4.4 months (IQR: 2.1-8.2) and 6.7 months (IQR: 3.9-12.6), respectively (χ2=4.372, P=0.037).Most of the adverse reactions during the treatment of the two groups were grades 1-2.In addition, no significant difference in the incidence of adverse reactions was found between two groups (P > 0.05). Conclusion Compared with fruquintinib alone, fruquintinib combined with sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy, and adverse drug reactions can be controlled.
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Objective To investigate the prevalence and epidemiological characteristics of taeniasis and cysticercosis among residents in Tibetan agricultural areas of Sichuan Province, so as to provide insights for the prevention and control of taeniasis and cysticercosis. Methods From 2016 to 2022, Kangding City, Daocheng County, Derong County, Ruoergai County and Muli Tibetan Autonomous County were sampled from Tibetan agricultural areas of Ganzi Tibetan Autonomous Prefecture, Aba Tibetan and Qiang Autonomous Prefecture and Liangshan Yi Autonomous Prefecture in Sichuan Province, and 1 to 6 townships were sampled from each county (district), followed by 4 to 7 villages sampled from each township. Primary school children were sampled using a cluster sampling method, and permanent residents at ages of over 16 years were randomly sampled from each village. Participants’ demographics, history of tapeworm excretion during the past year and clinical symptoms and signs of cysticercosis were collected through questionnaire surveys, and participants’ stool and venous blood samples were collected. Taenia eggs were detected in stool samples using the direct smear method, and deworming was performed among taeniasis patients with areca nut-squash seeds. The tapeworm species were identified using a multiplex PCR assay, and serum specific IgG antibody against cysticercus was detected using enzyme-linked immunosorbent assay (ELISA). Results A total of 5 249 respondents participated in the questionnaire survey, including 603 respondents (11.5%) with a self-reported history of proglottids secretion during the past year. A total of 3 976 residents were subjected to stool examinations, and the detection of Taenia eggs was 6.5%. Of 258 participants undergoing deworming, there were 403 cases (94.2%) with excretions of Taenia worms or proglottids. The mean prevalence of taeniasis was 10.9% (439/4 043), and there were gender-, age- and region-specific prevalence rates of taeniasis (χ2 = 36.73, 126.31 and 163.41, all P values < 0.05). Multiplex PCR assays detected 41 cases with T. solium infections (12.5%), 197 cases with T. saginata infections (59.9%) and 91 cases with T. asiatica infections (27.6%) among 329 patients undergoing deworming, and there were region-specific prevalence rates of T. solium, T. saginata and T. asiatica infections (χ2 = 45.39, P < 0.05). In addition, the sero-prevalence of anti-cysticercus IgG antibody was 7.0% (345/4 933), and there were age- and region-specific sero-prevalence rates of anti-cysticercus IgG antibody (χ2 = 13.49 and 51.76, both P values < 0.05). Conclusions Multiple Taenia species are prevalent in Tibetan agricultural areas of Sichuan Province and the sero-prevalence of anti-cysticercus antibody is high among residents. Monitoring and control of taeniasis and cysticercosis should be strengthened.
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Objective To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions. Methods Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman’s rank correlation analysis. Results The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ2 = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ2 = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ2 = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ2 = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ2 = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ2 = 164.07, P < 0.05). Spearman’s rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs (rs = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock (rs = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge (rs = − 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock (rs = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge (rs = −0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals (rs = −0.750, P > 0.05). Conclusions The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.
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Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the "vector" of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.
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Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.
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Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.
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The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.
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OBJECTIVE@#Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis.@*METHODS@#The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5).@*RESULTS@#The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.@*CONCLUSION@#XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.
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Male , Mice , Animals , Stomach Neoplasms/genetics , Drugs, Chinese Herbal/pharmacology , Glycosylation , Cell Line, Tumor , Cadherins/metabolismABSTRACT
The study aims to investigate the anti-hepatic fibrosis and anti-inflammatory activities of palbinone, and to explore the internal regulatory mechanism, so as to lay an active foundation for its development as an anti-non-alcoholic steatohepatitis (NASH) candidate. First, sulforhodamine B (SRB) method was used to detect the effect of palbinone on the proliferation of human hepatic stellate cells LX-2 and rat hepatic stellate cells HSC-T6. Following, in the in vitro hepatic fibrosis cell model that activated by transforming growth factor beta 1 (TGF-β1), quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the inhibitory effect of different concentrations of palbinone on the transcription level and protein expression level of hepatic fibrosis markers. And the regulating mechanism of palbinone on fibrosis-related genes was analyzed at the same time. In addition, in the inflammatory cell model that induced by lipopolysaccharide (LPS) and nigericin, ELISA was used to detect the effect of palbinone on the released interleukin-1β (IL-1β) level. At the same time, Western blot was used to detect the effect of palbinone on the related proteins of inflammatory pathway. The results showed that palbinone could significantly inhibit the proliferation activity of LX-2 and HSC-T6, and their half maximal inhibitory concentration (IC50) values were (375.11 ± 55.45) and (260.27 ± 36.81) nmol·L-1, respectively. In addition, palbinone showed a dose-dependent inhibitory effect on the expression levels of TGF-β1-induced fibrosis-related genes, including collagen type Ⅰ α 1 (COL1A1), TGF-β1, α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP1). Mechanism study showed that palbinone may decrease the expression level of Yes-associated protein (YAP), thereby weakening its activation effect on the downstream fibrosis pathway. In addition, palbinone also exerted an anti-inflammatory effect by inhibiting the activity of nuclear factor kappa-B (NF-κB) signaling pathway and reducing inflammatory factors cysteinyl aspartate specific proteinase-1 (caspase-1) and IL-1β release. In conclusion, palbinone can not only inhibit the proliferation and activation of hepatic stellate cells by inhibiting the expression of YAP, but also inhibit the expression and release of inflammatory factors at the same time. All these studies provide theoretical support for the development of palbinone as an anti-nonalcoholic steatohepatitis drug.
ABSTRACT
OBJECTIVE@#To analyze the femoral head collapse and the operation of osteonecrosis of the femoral head (ONFH) in different Japanese Investigation Commitee (JIC) types, in order to summarize the prognostic rules of each type of ONFH, and explore the clinical significance of CT lateral subtypes based on reconstruction of necrotic area of C1 type and verify their clinical effect.@*METHODS@#A total of 119 patients (155 hips) with ONFH between May 2004 and December 2016 were enrolled in the study. The total hips consisted of 34 hips in type A, 33 in type B, 57 in type C1, and 31 in type C2, respectively. There was no significant difference in age, gender, affected side, or type of ONFH of the patients with differenct JIC types ( P>0.05). The 1-, 2-, and 5-year femoral head collapse and operation of different JIC types were analyzed, as well as the survival rate (with femoral head collapse as the end point) of hip joint between different JIC types, hormonal/non-hormonal ONFH, asymptomatic and symptomatic (pain duration >6 months or ≤6 months), and combined preserved angle (CPA) ≥118.725° and CPA<118.725°. JIC types with significant differences in subgroup surgery and collapse and with research value were selected. According to the location of the necrotic area on the surface of the femoral head, the JIC classification was divided into 5 subtypes in the lateral CT reconstruction, and the contour line of the necrotic area was extracted and matched to the standard femoral head model, and the necrosis of the five subtypes was presented by thermography. The 1-, 2-, and 5-year outcomes of femoral head collapse and operation in different lateral subtypes were analyzed, and the survival rates (with collapse of the femoral head as the end point) between CPA≥118.725° and CPA<118.725° hip in patients with this subtype were compared, as well as the survival rates of different lateral subtypes (with collapse and surgery as the end points, respectively).@*RESULTS@#The femoral head collapse rate and operation rate in the 1-, 2-, and 5-year were significantly higher in patients with JIC C2 type than in patients with other hip types ( P<0.05), while in patients with JIC C1 type than in patients with JIC types A and B ( P<0.05). The survival rate of patients with different JIC types was significantly different ( P<0.05), and the survival rate of patients with JIC types A, B, C1, and C2 decreased gradually. The survival rate of asymptomatic hip was significantly higher than that of symptomatic hip, and the survival rate of CPA≥118.725° was significantly higher than that of CPA<118.725° ( P<0.05). The lateral CT reconstruction of type C1 hip necrosis area was selected for further classification, including type 1 in 12 hips, type 2 in 20 hips, type 3 in 9 hips, type 4 in 9 hips, and type 5 in 7 hips. There were significant differences in the femoral head collapse rate and the operation rate among the subtypes after 5 years of follow-up ( P<0.05). The collapse rate and operation rate of types 4 and 5 were 0; the collapse rate and operation rate of type 3 were the highest; the collapse rate of type 2 was high, but the operation rate was lower than that of type 3; the collapse rate of type 1 was high, but the operation rate was 0. In JIC type C1 patients, the survival rate of the hip joint with CPA≥118.725° was significantly higher than that with CPA<118.725° ( P<0.05). In the follow-up with femoral head collapse as the end point, the survival rates of types 4 and 5 were all 100%, while the survival rates of types 1, 2, and 3 were all 0, and the difference was significant ( P<0.05). The survival rate of types 1, 4, and 5 was 100%, of type 3 was 0, and of type 2 was 60%, showing significant difference ( P<0.05).@*CONCLUSION@#JIC types A and B can be treated by non-surgical treatment, while type C2 can be treated by surgical treatment with hip preservation. Type C1 was classified into 5 subtypes by CT lateral classification, type 3 has the highest risk of femoral head collapse, types 4 and 5 have low risk of femoral head collapse and operation, type 1 has high femoral head collapse rate but low risk of operation; type 2 has high collapse rate, but the operation rate is close to the average of JIC type C1, which still needs to be further studied.