Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective:To explore the relationship between relapse tendency and psychological craving in fe-male methamphetamine(MA)-dependent young adults,focusing on the roles of self-control and future time per-spective.Methods:A total of 340 MA-dependent young adults from two women's compulsory isolation drug reha-bilitation centers in Sichuan Province were included.Participants were assessed with the Relapse Tendency Ques-tionnaire(RTQ),Obsessive Compulsive Drug Use Scale(OCDUS),Drug Abuser Self-Control Ability Question-naire(DASAQ)and General Future Time Perspective Scale(GFTPQ).The moderated mediation model was ana-lyzed by using the SPSS macro program PROCESS(version4.2).Results:The RTQ scores were positively correla-ted with the OCDUS scores(r=0.45,P＜0.001).The DASAQ scores partially mediated the relationship between the scores of OCDUS and RTQ,accounted for 37.91％of the total effect.The GFTP scores moderated the relation-ship between the scores of the OCDUS,DASAQ and RTQ(β=-0.18,0.19,P＜0.001).Conclusion:The influ-ence of psychological craving on relapse tendency in female MA-dependent young adults exhibits a moderated me-diating effect,suggesting the potential of enhancing self-control and future time perspective for preventing relapse and improving detoxification efficiency.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep

With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.
Ancylostomatoidea/genetics* ; Animals ; Feces ; Hookworm Infections/diagnosis* ; Humans ; Necator americanus/genetics* ; Polymerase Chain Reaction

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.

Objective:To understand the occurrence and the clinical characteristics of meropenem-related central nervous system (CNS) adverse reactions.Methods:Using the hospital information system, the electronic medical records of patients who were hospitalized in the Department of Respiratory, the 305 Hospital of the People′s Liberation Army from January 2016 to December 2021 and received meropenem were collected. Medical records of patients who developed CNS symptoms after meropenem administration were screened and analyzed retrospectively. The data extracted from the medical records mainly included gender, age, infectious diseases, underlying diseases, renal function at admission [serum creatinine, endogenous creatinine clearance (Ccr)] in the patient, the application of meropenem (dose, whether dose was adjusted according to Ccr), and the occurrence (occurrence time, main clinical manifestations, etc.), treatment, and outcome of meropenem-related CNS adverse reaction. The incidence of meropenem-related CNS adverse reactions was calculated, and their clinical characteristics was descriptively analyzed.Results:A total of 636 patients used meropenem during the set period and 17 of them developed meropenem-related CNS adverse reactions, with an incidence of 2.7%. Among 17 patients, 10 were male and 7 were female, aged from 74 to 94 years with a median age of 86 years. Thirteen patients had pulmonary infection (one with urinary system infection) and 4 had acute exacerbation of chronic obstructive pulmonary disease (2 with type Ⅱ respiratory failure); 14 patients had combined renal insufficiency (10 of them had a Cc r <50 ml/min) and 5 had sequelae of cerebral infarction. Ten patients were with Cc r <50 ml/min and 3 of them did not adjust the dose of meropenem according to Ccr, resulting in excessive dosage. The time to onset of CNS symptoms in 17 patients ranged from 1 to 7 days after starting meropenem, with a median time of 3 days. Twelve patients presented mainly with psychiatric disorders (including delirium, agitation, hyperarousal, hallucinations, confusion and sleep reversal, etc.), and 5 with limb or orolingual convulsions. Meropenem was discontinued in all 17 patients after the onset of CNS symptoms and 5 of them were given symptomatic treatments. Symptoms were relieved after 1-7 days in all the patients, with a median time of 3 days. Conclusions:Meropenem-related CNS adverse reactions are more common in elderly patients and patients with renal insufficiency, respiratory failure, and a history of CNS diseases. The main manifestations are mental disorders and convulsions, which mostly occur within one week of drug use. Stopping meropenem in time and receiving appropriate symptomatic treatments contribute a good prognosis in patients.

Objective:To understand the occurrence and the clinical characteristics of meropenem-related central nervous system (CNS) adverse reactions.Methods:Using the hospital information system, the electronic medical records of patients who were hospitalized in the Department of Respiratory, the 305 Hospital of the People′s Liberation Army from January 2016 to December 2021 and received meropenem were collected. Medical records of patients who developed CNS symptoms after meropenem administration were screened and analyzed retrospectively. The data extracted from the medical records mainly included gender, age, infectious diseases, underlying diseases, renal function at admission [serum creatinine, endogenous creatinine clearance (Ccr)] in the patient, the application of meropenem (dose, whether dose was adjusted according to Ccr), and the occurrence (occurrence time, main clinical manifestations, etc.), treatment, and outcome of meropenem-related CNS adverse reaction. The incidence of meropenem-related CNS adverse reactions was calculated, and their clinical characteristics was descriptively analyzed.Results:A total of 636 patients used meropenem during the set period and 17 of them developed meropenem-related CNS adverse reactions, with an incidence of 2.7%. Among 17 patients, 10 were male and 7 were female, aged from 74 to 94 years with a median age of 86 years. Thirteen patients had pulmonary infection (one with urinary system infection) and 4 had acute exacerbation of chronic obstructive pulmonary disease (2 with type Ⅱ respiratory failure); 14 patients had combined renal insufficiency (10 of them had a Cc r <50 ml/min) and 5 had sequelae of cerebral infarction. Ten patients were with Cc r <50 ml/min and 3 of them did not adjust the dose of meropenem according to Ccr, resulting in excessive dosage. The time to onset of CNS symptoms in 17 patients ranged from 1 to 7 days after starting meropenem, with a median time of 3 days. Twelve patients presented mainly with psychiatric disorders (including delirium, agitation, hyperarousal, hallucinations, confusion and sleep reversal, etc.), and 5 with limb or orolingual convulsions. Meropenem was discontinued in all 17 patients after the onset of CNS symptoms and 5 of them were given symptomatic treatments. Symptoms were relieved after 1-7 days in all the patients, with a median time of 3 days. Conclusions:Meropenem-related CNS adverse reactions are more common in elderly patients and patients with renal insufficiency, respiratory failure, and a history of CNS diseases. The main manifestations are mental disorders and convulsions, which mostly occur within one week of drug use. Stopping meropenem in time and receiving appropriate symptomatic treatments contribute a good prognosis in patients.

Objective To investigate the relationship between low serum calcium concentration and hematoma volume in patients with intracerebral hemorrhage.Methods Between January 2012 and October 2014,870 consecutive patients with intracerebral hemorrhage admitted to the Department of Neurosurgery,West China Hospital,Sichuan University were enrolled prospectively.The patients completed laboratory serum calcium concentration and head CT examinations within 24 h after attack,and the baseline data and laboratory findings were collected.According to the normal reference value of laboratory serum calcium concentration,the patients were divided into a hypocalcemia calcium group (<2.1 mmol/L;n=193) and a normal calcium group (2.1-2.7 mmol/L;n=677).Spearman correlation analysis was used to analyze the correlation between the blood serum calcium concentration and the hematoma volume on admission.Results (1) The hypocalcemia group compared with normal calcium group,the proportion of male patients was high (73.6% [n=142] vs.66.0% [n=447]),the median score for Glasgow coma scale was lower (9 vs.11),and the median hematoma volume was larger (33.86 cm3 vs.21.69 cm3).The differences were statistically significant (all P<0.05).(2) Spearman correlation analysis showed that the lower serum calcium level on admission was weakly negatively correlated with the volume of hematoma in patients with intracerebral hemorrhage (r=-0.113,P<0.01).Conclusion The study suggested that the hypocalcemia on admission was mostly males in patients with intracerebral hemorrhage,the condition was serious,the volume of hematoma was larger,and the lower serum calcium concentration was negatively correlated with the hematoma volume.

Objective To investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading. Methods Bovine meniscus explants were subjected to 25%strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release. Results The number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25%abnormal pressure stimulation (n=3, P<0.05). Conclusion HBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.

Objective To investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading. Methods Bovine meniscus explants were subjected to 25%strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release. Results The number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25%abnormal pressure stimulation (n=3, P<0.05). Conclusion HBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.