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OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin, granulocyte colony-stimulating factor and cytarabine (CAG) regimen in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS CNKI, Wanfang data, VIP, Sino Med, PubMed, Embase, the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th, 2023. Randomized controlled trials (RCTs) about thalidomide combined with CAG regimen (trial group) versus CAG regimen (control group) in the treatment of elderly AML patients were collected, and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally, 7 RCTs were included, with a total of 601 patients, including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z=4.75, P<0.000 01, OR=2.80, 95%CI (1.83,4.28)], complete remission rate [Z=2.82, P=0.005, OR=1.61, 95%CI (1.16, 2.25)], and improving platelet count [Z=2.70, P=0.007, MD=64.02, 95%CI (17.53, 110.51)], vascular endothelial growth factor [Z=13.63,P<0.000 01, MD=-65.17, 95%CI(-74.54, -55.80)], vascular endothelial growth factor receptor [Z=12.03, P< 0.000 01, MD=-499.01, 95%CI (-580.31, -417.71)] and basic fibroblast growth factor [Z=4.17, P<0.000 1,MD=-0.23, 95%CI(-0.35, -0.12)]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z=0.99, P=0.32, OR=0.52, 95%CI(0.14,1.89)], nausea and vomiting [Z= 1.06, P=0.29, OR=0.66, 95%CI (0.30,1.43)], constipation or diarrhea [Z=0.92, P=0.36, OR=0.65, 95%CI(0.26, 1.63)], drowsiness [Z=1.38, P=0.17, OR=0.57, 95%CI(0.26, 1.27)] or myelosuppression [Z=0.88,P=0.38,OR=0.68,95%CI(0.28, 1.62)]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.
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Objective To observe the value of 18F-FDG PET/CT combined with tumor markers for diagnosis of non stageⅠ A limited-stage small cell lung cancer(LS-SCLC).Methods Totally 87 cases of non stage Ⅰ A LS-SCLC(LS-SCLC group),137 of non stage Ⅰ A non-small cell lung cancer(NSCLC,NSCLC group)and 48 cases of pulmonary inflammatory lesions(inflammatory group)were enrolled.Patients'general data,tumor marker levels and PET/CT findings were comparatively analyzed.Logistic regression analysis was performed to evaluate the efficacy of parameters for diagnosing non stage Ⅰ A LS-SCLC.Results There were significant differences of patients'age,neuron-specific enolase(NSE),pro-gastrin-releasing peptide(ProGRP),carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCCA)and cytokeratin-19-fragment(CYFRA21-1),as well as of the maximum lesion diameter,maximum standard uptake value(SUVmax),morphology,spiculation sign,relationship between long axis and bronchus,lymph node fusion and proportion of lymph node with higher SUVmax than primary lesion among 3 groups(all P<0.05).The area under the curve(AUC)of the combination of spiculation sign,NSE>23.5 μg/L,ProGRP>111.8 ng/L,SCCA≤2.5 μg/L and CYFRA21-1≤7.4 μg/L for differentiating LS-SCLC and NSCLC was 0.91,higher than that of each single parameter(all P<0.05).AUC of the combination of SUVmax>8.1,NSE>19.4 μg/L,ProGRP>72.5 ng/L and lymph node fusion for differentiating LS-SCLC and pulmonary inflammatory lesions was 0.99,higher than each single parameter(all P<0.05).Conclusion 18F-FDG PET/CT combined with tumor markers ProGRP and NSE was helpful for diagnosing non stage ⅠA LS-SCLC.
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Objective:To explore the value of 18F-FDG PET/CT combined with pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in diagnosis and differential diagnosis of stageⅠA small cell lung cancer (SCLC). Methods:From June 2017 to October 2021, 113 patients (75 males, 38 females; age 32-79 years) with stageⅠA lung cancer (70 with adenocarcinoma, 25 with squamous cell carcinoma, 18 with SCLC; patients with adenocarcinoma and squamous cell carcinoma were combined into non-SCLC (NSCLC) group) and 30 patients with benign pulmonary nodule (21 males, 9 females; age 37-77 years) from the Affiliated Qingdao Central Hospital of Qingdao University were retrospectively analyzed. All patients were examined by 18F-FDG PET/CT and serum tumor markers associated with lung cancer. Differences of the clinical, imaging and tumor markers data among different groups were analyzed by χ2 test, Fisher exact test and Kruskal-Wallis rank sum test. Independent risk factors were analyzed by logistic regression analysis and ROC curve analysis was used to analyze the value of different predictive factors in diagnosis and differential diagnosis of SCLC. Results:There were significant differences in SUV max, lobulation sign, spiculation sign, calcification, pleural traction sign, ProGRP, NSE and carcinoembryonic antigen (CEA) among SCLC, NSCLC and benign nodules groups ( H values: 14.06-20.54, χ2 values: 8.16-14.95, all P<0.05), in which lobulation sign of SCLC was more than that of benign nodules (12/18 vs 26.7%(8/30); χ2=7.41, P=0.007), spiculation sign (2/18 vs 51.6%(49/95); χ2=10.01, P=0.002) and pleural traction sign (1/18 vs 35.8%(34/95); χ2=6.47, P=0.011) were less than those of NSCLC, SUV max was higher than that of benign nodules (7.4(5.8, 9.0) vs 2.3(1.4, 5.1); H=51.82, P<0.001), ProGRP was higher than that of NSCLC and benign nodules (64.0(40.1, 84.8) vs 38.7(26.9, 47.6), 36.7(29.1, 40.5) ng/L; H values: 36.13, 43.96, P values: 0.002, 0.001) and NSE was higher than that of benign nodules (12.4(10.9, 14.5) vs 7.4(5.4, 11.8) μg/L; H=40.53, P=0.001). When differentiated SCLC from NSCLC, spiculation sign (odds ratio ( OR)=0.043, 95% CI: 0.004-0.450, P=0.009) and ProGRP ( OR=1.083, 95% CI: 1.035-1.133, P<0.001) were independent risk factors for SCLC, and the AUC of the two factors combination was 0.875, with the sensitivity and specificity of 14/18 and 84.2%(80/95). When differentiated SCLC from benign nodules, SUV max( OR=2.706, 95% CI: 1.099-6.662, P=0.030), ProGRP ( OR=1.165, 95% CI: 1.009-1.344, P=0.038) and NSE ( OR=1.639, 95% CI: 1.016-2.645, P=0.043) were independent risk factors for SCLC, and the AUC of the three factors combination was 0.985, with the sensitivity and specificity of 17/18 and 96.7%(29/30). Conclusion:18F-FDG PET/CT combined with tumor markers ProGRP and NSE is helpful to improve the diagnosis and differential diagnosis of stage ⅠA SCLC.
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Objective To investigate the protective effect of geniposide against diabetic rats with skin ulcer and the mechanism.Methods Rats were divided into a normal group,model group,and geniposide subgroups(Gen(L):200 mg/kg;Gen(H):500 mg/kg).Diabetic rats were treated with normal saline or geniposide by intragastric administration(n=6).Treatments were administered once a day,and the wound healing and inflammation of each group were recorded every day.After 7 days of treatment for diabetic skin ulcers,the wound area,tissue sections,TUNEL staining and Western blot were used to quantitatively analyze changes in wound healing,apoptosis,and related regulatory protein expression.Results Compared with the model group,the group receiving orally administered geniposide(200 and 500 mg/kg)showed significantly improved wound healing and increased contraction of the injured area.In terms of skin wound apoptosis in diabetic rats,TUNEL-positive cells were significantly reduced in geniposide subgroups(P<0.05).Geniposide significantly inhibited skin inflammation and promoted wound repair,which may be related to promotion of PI3K and Akt phosphorylation.Conclusions Geniposide promoted skin wound repair in diabetic rats by inhibiting inflammatory responses and apoptosis.
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Objective:To explore the value of 18F-fluorodexyglucose (FDG) PET/CT combined with integrated contrast-enhanced CT on the diagnosis of hepatic epithelioid hemangioendothelioma(HEH). Methods:Six patients (2 males, 4 females, age: (41.0±5.6) years) histopathologically confirmed to be HEH in Qingdao Central Hospital between November 2013 and November 2018 were retrospectively analyzed. All patients underwent 18F-FDG PET/CT dual-phase imaging and three-phase dynamic enhanced scanning with integrated CT. Characteristics of 18F-FDG PET/CT and contrast-enhanced CT images were classified and analyzed. Results:All 6 patients had multi-lesions (30 lesions in total). The capsule retraction sign was found in 16.7% (5/30) lesions, target sign was found in 33.3% (10/30) lesions, and " lollipop sign" was found in 13.3% (4/30) lesions. There were three ways of enhancement showed by CT: mild progressive enhancement, delayed enhancement, and black target sign/white target sign in the portal phase. Among the 30 lesions, 66.7% (20/30) had higher 18F-FDG uptake than liver parenchyma, with maximum standardized uptake value (SUV max) of 4.18±0.64 during routine imaging and 4.23±0.70 during delayed imaging, and the retention index was 0.65(-1.88, 4.60). The rest 33.3% (10/30) showed similar 18F-FDG uptake to liver parenchyma, with SUV max of 2.75±0.52 during routine imaging, and 2.78±0.55 during delayed imaging. The uptake of 18F-FDG increased with time in 22 lesions and decreased in 8 lesions. In the metabolically heterogeneous lesions, the relatively high-metabolization site was also the site with higher peak enhancement; in the lesions with uniform metabolism, the CT enhancement was also uniform. Bilateral pulmonary metastases were found in 2/6 patients. Conclusion:18F-FDG PET/CT dual-phase imaging combined with CT three-phase dynamic enhanced scanning is helpful in accurate diagnosis of HEH and could show extrahepatic metastases.
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Objective:To investigate the role of neurite outgrowth inhibitor (Nogo)-oligodendrocyte myelin glycoprotein (Omgp)/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase (Rock) signaling pathway in acute brain injury of carbon monoxide (CO) poisoning rats and treatment feasibility with Rho kinase inhibitor hydrochloride fasudil.Methods:According to random number table method, 135 healthy male SD rats were divided into three groups: a normal control group, a CO poisoning group and a fasudil treatment group ( n=45). Rat models of acute severe CO poisoning were established in the CO poisoning group and fasudil treatment group by inhalation method in a hyperbaric oxygen chamber. All rats received hyperbaric oxygen therapy for two weeks. Rats in the farsudil treatment group were intraperitoneally injected with hydrochloride farsudil for intervention (15 mg/[kg·d], once a d for 2 weeks), while those in the CO poisoning and normal control groups received the same volume of normal saline. The ultrastructures of rat brain tissues were observed by transmission electron microscopy one week after modeling. Staining intensities of Nogo- and OMgp-positive cells were detected by immunohistochemistry, and those of Rock-positive cells were analyzed by immunofluorescence one d, one week, one month and two months after modeling. The protein expressions of Nogo, OMgp and Rock in brain tissues were detected by Western blotting one d, one week, one month and two months after modeling. Results:In the CO poisoning group, the ultrastructures of brain tissues and blood-brain barrier were damaged obviously, and the changes in nucleus, mitochondria and synaptic structure were obvious; while fasudil treatment could effectively maintain the integrity of ultrastructures and functions of brain tissues, and reduce brain edema. One d, one week, one month and two months after modeling, the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the CO poisoning group were significantly higher than those in the normal control group at the same time point ( P<0.05); the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the fasudil treatment group were significantly lower than those in the CO poisoning group at the same time point ( P<0.05). Conclusion:The activation of Nogo-OMgp/Rho-Rock signaling pathway related molecules (Nogo, OMgp and Rock) is closely related to acute brain injury caused by CO poisoning; hydrochloride fasudil can effectively down-regulate the protein expressions of Nogo, OMgp and Rock, therefore obviously alleviate brain injury after CO poisoning.
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Objective To evaluate the application value of identification on drown by detection 16SrDNA of the diatoms in rabbits' internal organs in summer month of July and winter month of December in YongJiang River of Ningbo. Methods 60 Rabbits were randomly and medially divided into three groups in summer and winter: drowning group, postmortem immersion group and using only lethal aeroembolism as control group. Specimen including heart, liver, lung and kidney from each rabbit were tested with diatom 16SrDNA PCR method. Results Compared with postmortem immersion group, detection rate of diatom 16SrDNA of heart, liver, lung, renal tissue in drowning group was significantly higher than that in summer month of July (P<0.05), In December, the 16SrDNA of the drowning group was detected in heart and lung tissues, There was no significant difference compared with postmortem immersion group (P>0.05) In summer month of July, detection rate of 16SrDNA of heart, liver, lung, renal tissues in drowning group was significantly higher than that in winter month of December (P<0.05). Diatom 16SrDNA of heart, liver, lung, kidney tissues in air embolism group were not detected In summer month of July and winter month of December. Conclusion With the higher detection rate of diatom 16SrDNA in drowning rabbit in summer, the diatom 16SrDNA PCR method can be used for the diagnosis of drowning in Yongjiang River of Ningbo; while in winter , it should be carefully apllied with the lower detection rate of diatom 16SrDNA.
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Type II innate lymphoid cells ( ILC2s) are widely distributed in the blood , intestines, trachea, lung, spleen, liver, animal fat and skin, and involved in the innate immune responses .ILC2s have attracted much atten-tion for its important roles in the conversion of white adipose to beige adipose .Studies have shown that ILC2s are essential for the proliferation and differentiation of adipocyte precursor cells , and they also play a vital role in anti-parasitic infection and allergic inflammation .This review discusses the discovery , differentiation , development , distribution and function of ILC2s, and their relationships with the browning of white adipose tissue for providing valuable references on understanding the pathogenesis , prevention and treatment of obesity and fat metabolism disorders .
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Objective To investigate the effect of acupunctures variable with stages on lumbar intervertebral dise protrusion (LIDP). Methods 98 LIDP patients in our hospital from October, 2014 to July, 2015 were randomly divided into control group (n=49) and observa-tion group (n=49) according to the sequence of first diagnosis time. The control group received routine acupuncture, and the observation group acupunctured at Ouch point and Huantiao point (GB30) with different acupuncture according to manifestations and courses. Modified Yang acupuncture was adopted in acute phase, triple acupuncture was used in remittent phase, and lateral needling was used in the recovery phase. They were both treated once a day, 7 days as a course for 3 courses with 2 days of interval. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and clinical effects were assessed before and 1, 2, 3 courses after treatment. Results Both VAS and ODI scores im-proved after treatment (F>7.12, P4.43, P<0.05). The efficiency was higher in the observation group than in the control group (χ2=5.594, P<0.05). Conclusion Compared with normal acupuncture, the acupunctures variable with stages is more effective on LIDP than routine.
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Aim To determine the possibilities and mechanisms of EGFR, a receptor protein tyrosine kinase associated with many important cellular processes re-sponsible for cardiovascular remodeling in renovascular hypertensive rats. Methods 2K1C hypertensive rats were used in the present study. Blood pressure was measured with the tail-cuff method. LVMI and his-topathological changes in the cardiovascular system were analysed. EGFR expressions of aorta and myocar-dium as well as phosphorylation levels of ERK in hy-pertensive rats were detected by immunohistochemistry and Western blot analysis, respectively. Results Sys-tolic blood pressure was markedly increased 2 weeks after 2K1C surgery. Cardiovascular remodeling induced by hypertension was confirmed by elevated LVMI, pro-liferation of collagen fibers in myocardial interstitium, histopathological changes in cardiovascular system and increased IMT of thoracic aorta 6 weeks after 2 K1 C surgery. Compared with sham rats, EGFR expression in the ventricular myocardium of 2 K1 C rats was signifi-cantly increased at 6 weeks ( P<0. 05 ) , and the EG-FR/GAPDH ratio was higher in 2 K1 C rats with higher systolic blood pressure ( P < 0. 05 ) . Phosphorylation level of ERK 1/2 was upregulated correspondingly in 2 K1 C rats ( P <0. 01 ) . Increased EGFR expression was also found in aortas of 2K1C rats, particularly in tunica intima and media. Conclusion EGFR and its down-stream kinases ERK 1/2 are involved in cardio-vascular remodeling in association with the severity of hypertension in renovascular hypertensive rats.
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Objective To evaluate the efficacy and safety of Sheng-qi-zhuang-yang formula combined with specific immunotherapy (SIT) with standardized house dust mite vaccine on allergic asthmatic children. Methods Participants were 100 children with mild to moderate allergic asthma , who were receiving SIT at Guangdong Provincial Hospital of Chinese Medicine from Jan 2011 to Dec 2013 , who were divided into treatment group and control group. Patients in the treatment group received Sheng-qi-zhuang-yang Decoction combined with SIT while patients in the control group received SIT alone. Asthma symptom scores, respiratory function and related adverse events were compared before and after treatment, between groups. Results The desensitization treatment functions was ahead of time than expected in both groups. There is no significant difference between groups in terms of respiratory function and adverse effects. Conclusion Sheng-qi-zhuang-yang decoction combined with SIT for allergic asthmatic children seems to advance clinical effect without increasing adverse events. Further large scale clinical trial is required to confirm this.
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Objective To investigate the effects of electroacupuncture (EA) on spatial learning and memory ability, long-term potentiation (LTP) and synaptophysin (Syp) levels in the dentate gyrus of the hippocampus.Methods Forty Sprague-Dawley rats were randomly divided into a sham-operated control group, a model group, an EA group and a medication group. A rat model of vascular dementia (VD) was established by repeated ischemia and reperfusion after pretreatment with sodium nitroprusside. EA was applied to the rat homologues of the human "Baihui" (GV20) and "Dazhui" (DU14) acupoints of the rats in the EA group for 20 min, once daily for 10 d.Morris water maze tests were conducted for evaluating the rats,learning and memory ability. LTP in the hippocampal dentate gyrus was recorded as an electrophysiological index for evaluating learning and memory. Antigenic Syp produced in hippocampal tissue was examined with immunohistochemical assays. Results In comparison the with model group, escape latency (EL) shortened and target-platform crossing times increased significantly in the EA and medication groups. After high frequency stimulation the population spike (PS) latency shortened in the EA group compared with the model group, and the excitatory postsynaptic potential (EPSP) slope and PS amplitude increased.All of these differences were statistically significant. Syp positive cells also increased significantly in the EA-treated rats. Conclusions EA can increase Syp expression and improve the learning and memory ability of rats with this model of VD. EA could facilitate the induction and maintenance of LTP in the dentate gyrus of the hippocampus through influencing synaptic transmission.
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Objective To investigate the adjuvant effect of dimo-thylidioctyl ammonium bromide (DDA) and/or DDA-BCG polysaccharide nucleic acid( BCG-PSN), which was combined with a Mycobacterium tuberculosis fusion protein AMM ( Ag 8 5 B - MPT64190-198 - Mtb8.4 ) to boost BCG primed immunization. Methods DDA with or without BCG PSN was mixed with the fusion protein AMM to construct the boosting vaccine. Mice were immunized with BCG and then boosted twice with AMM formulated with the adjuvant DDA with or without BCG-PSN. PBS or BCG vaccination without boosting was used as control. The humoral and cell-mediated immune responses were analyzed by ELISA and ELISPOT. Moreover, the protective efficacy of BCG prime-AMM subunit vaccine boosting against Mycobacterium tuberculosis infection was analyzed. Results With in vitro stimulation of Ag85B and PPD( purified protein derivative) antigen, the number of IFN-γ secreting cells from the mice boosted twice by AMM/DDA/BCG-PSN and AMM/DDA were higher than BCG and PBS group (P <0.05). The CFU in lungs of mice boosted with AMM/DDA/BCG-PSN was less than that of PBS group(P <0.05), while the CFU of AMM/DDA-boosted mice was less than that of BCG and PBS group(P < 0.05).However, fewer lesions were seen in lungs of mice immunized with BCG alone or BCG-prime-AMM/DDA/BCG-PSN boosting than the other groups. Conclusion DDA is an idea adjuvant for tuberculosis subunit vaccine;BCG-PSN might play a role in alleviating the immunity-mediated pathology.
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Objective To investigate the boosting efficiency of a subunit vaccine consisting of the fusion protein Ag85B-Mpt64190-198-Mth8.4 (AMM) , dimethyl-dioctyldecyl ammonium bromide (DDA) and BCG polysaceharide nucleic acid (BCG-PSN) on the primed inoculation with BCG. Methods The AMM subunit vaccine was composed of fusion protein AMM, adjuvant DDA and BCG-PSN. The first mouse experi-mental group was immunized with BCG first, then boosted with the AMM subanit vaccine in the 10th week. The second experimental group was boosted with the AMM subunit vaccine in the 8th week and the 10th week respectively with a two weeks interval after the primed with BCG. Two control groups were treated re-spectively with physiological saline alone and BCG alone. After the primed inoculation, ELISPOT and ELISA were used for the detection of the cell-mediated and humoral immune response in week 14 and week 22 re-spectively. Furthermore, the immunized mice were challenged with live BCG to mimic tuberculosis infection in the 22nd week after the primed inoculation. Subsequently the T cell typing and humoral response were de-tected by flow cytometry and ELISA, respectively. Results ( 1 ) The level of secreting IFN-γ: 14 weeks af-ter the primed inoculation,with the stimulation of the specific antigen-Ag85B, the number of cells secreting IFN-γ in the second experimental group (135±14) was more than BCG alone immunized group (19±16), t = 10. 98, P < 0.01. In the 22nd week, the number of cells secreting IFN-γ in the second experimental group (208±11) was still more than BCG alone group (57±18), t =6.43, P <0.01. (2) The level of humoral immune response: the IgG1 antibody titer in the second experimental group was obviously higher than that in the first experimental group. However, the ratio of IgG2a to IgG1, as the index reflecting the Thl-type immune response, in the experimental group 2 was lower than that in the experimental group 1. (3) The contents of CD4+ CD25+ T cells after challenged with live BCG strain: the first and the second ex-perimental groups were both higher than the BCG alone group (t1 = 3.08, t2 = 3.16, P < 0.05 ). Conclu-sion Boosting the BCG-pfimed mice with tuberculosis AMM subunit vaccine twice can induce higher level of cell-mediated and humoral immune response than BCG alone, which could activate the regulative immune response at the same time.
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Objective To construct protective immunity to Mycobncterium tuberculosis latent infection, a novel fusion protein consisting of HspX, the 190 to 198 peptide of Mpt64 and Ag85B, which were confirmed to be the effective protective antigens mainly expressed in the dormancy and exponential phase of growth, was constructed and its immunogenicity was investigated. Methods Ag85B and Mpt64190-198-HspX sequences were amplified by PCR and cloned into plasmids pET-28a. The fusion protein, Ag85BMpt64190-198-HspX (AMH) was expressed in E. coli BL21 and purified with Ni-NTA resins. C57BL/6 mice were immunized three times at 2-week intervals subcutaneously with AMH formulated with the adjuvant composed of dimethyl-dioctyldecyl ammonium bromide (DDA) and BCG polysaccharide nucleic acid (BCGPSN). Humoral and cell-mediated immunity responses were analyzed at five weeks after the last injection. Results AMH was expressed stably in E. coli and could be purified well by Ni-NTA affinity chromatography. C57BL/6 mice immunized with AMH subunit vaccine generated specific cellular and humoral immunologic response to the stimulation of Ag85B, Mpt64190-198 and HspX. Conclusion It suggested that AMH was a promising candidate antigen of tuberculosis subunit vaccine.
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Freshwater crabs and snails were collected from Ninghai County in Zhejiang Province, and examined respectively for Paragonimus metacercariae and cercariae. Among 97 freshwater crabs found, the prevalence was 11.3% (11/97) with a mean intensity of 1 metacercariae per crab. It was 10.2% (5/49) and 20.2% (4/20) in the groups weighted 5-15 g and 15-25 g respectively, with an average intensity of 1, and no metacercariae were found in weight group of 25-35 g. Two positive crabs were found from 20 crabs with a low weight (