BACKGROUND:Pressing massage applied to myofascial trigger points(MTrPs)has shown clear effect in relieving pain.However,further research is needed to investigate the effects of different levels of pressure applied during the massage. OBJECTIVE:To investigate the different strength of pressing on MTrPs in rats with chronic pain. METHODS:Sixty SPF-rated male Sprague-Dawley rats were randomly divided into a blank group of 10 rats not involved in MTrPs modeling and 50 rats involved in modeling.The MTrPs model was established in the left medial thigh muscle of rats by blunt strikes combined with centrifugal exercise and 40 rats that met the evaluation criteria after modeling were randomly divided into model group,light press group,medium press group and heavy press group,with 10 rats in each group.The rats in the blank group and the model group were not intervened,while the rats in the light press group,the medium press group and the heavy press group were intervened with a homemade press stimulator with light force(0.3 kg),medium force(0.5 kg)and heavy force(0.7 kg)to MTrPs.The intervention time was 7.5 minutes per session,with one session every other day,totaling seven sessions.Electromyogram,soft tissue tension and mechanical pain threshold were detected by electrophysiological instruments,soft tissue tension tester,and pressure painmeter,respectively.After the intervention,in the blank group,muscle tissue was taken from the inside of the left thigh,while in the other groups,MTrPs tissue was taken.The pathological morphology was observed by hematoxylin-eosin staining,while enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of cyclooxygenase-2,prostaglandin E2 and bradykinin. RESULTS AND CONCLUSION:Compared with the blank group,the model group had lower mechanical pain thresholds,higher soft tissue tone,higher amplitude frequency of spontaneous electrical activity,significant pathomorphological changes,and increased levels of cyclooxygenase-2,prostaglandin E2 and bradykinin(P<0.05).Compared with the model group,the medium press group and the heavy press group showed increased mechanical pain thresholds,decreased soft tissue tension,decreased spontaneous potential frequency amplitude,and decreased levels of cyclooxygenase-2,prostaglandin E2 and bradykinin(P<0.05),and significant recovery on pathomorphological changes.No significant changes in the above indicators were observed in the light press group(P>0.05).Compared with the medium press group,the heavy press group showed better improvement in the above indicators(P<0.05).To conclude,moderate to heavy pressing is often required to alleviate MTrPs pain.

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 develop an intelligent horizontal rotating cell culture device with high modularity,easy operation,easy disinfection,low cost and high stability.Methods The cell culture device consisted of a rotating culture module,a dirve module,a control module and control software,with the shells of all the modules being manufactured by 3D printing.The rotating culture module was composed of a tubular electrospun scaffold,a cell culture chamber,a magnetic coupling rotor and polypropylene pipeline;the drive module was made up of a N20 reduction motor and a magnetic coupling rotor;the control module included an ESP-8266 chip and a printed circuit board;the control software was developed with Blinker IoT platform and C++language.The device was used to culture human intrahepatic bile duct epithelial cells to verify its effects.Results Light microscopy and scanning electron microscopy images showed that a uniform and continuous cell layer was formed on the surface of the tubular electrospun scaffold.Conclusion The intelligent horizontal rotating cell culture device achieves uniform growth of cells on the inner surface of tubular electrospun scaffolds,and can be used as an effective platform for cell culture on tubular scaffolds.[Chinese Medical Equipment Journal,2024,45(9):41-45]

Objective To investigate the clinical effect of anterior cervical discectomy and fusion(ACDF)in the treatment of cervical spondylosis of vertebral artery type(CSA).Methods The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed.There were 25 males and 17 females,aged from 30 to 74 years old with an average of(53.9±11.0)years old.There were 18 cases with single-segment lesions,17 cases with two-segment lesions,and 7 cases with three-segment lesions.The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score(CHE),the Neck Disability Index(NDI)and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months.Results All 42 ACDF patients were followed up for 6 to 30 months with an average of(14.0±5.2)months.The operative time ranged from 95 to 220 min with an average of(160.38±36.77)min,the intraoperative blood loss ranged from 30 to 85 ml with an average of(53.60±18.98)ml.Tow patients had mild postoperative dysphagia,which improved with symptomatic treatment such as nebulized inhalation.CHE score decreased from(4.05±0.96)preoperatively to(2.40±0.70)at 6 months postoperatively(t=12.97,P＜0.05).The number of improved vertigo at 6 months postoperatively was 38,with an im-provement rate of 90.5％.NDI score was reduced from(34.43±8.04)preoperatively to(20.76±3.91)at 6 months postopera-tively(t=1 1.83,P＜0.05).The cervical curvature Cobb angle improved from(8.04±6.70)° preoperatively to(12.42±5.23)° at 6 months postoperatively(t=-15.96,P＜0.05).Conclusion The ACDF procedure has outstanding clinical efficacy in treating CSA.The operation can rapidly relieve patients'episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature.However,it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in pa-tients,and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.
Humans ; Middle Aged ; Receptors, Chimeric Antigen/therapeutic use* ; Retrospective Studies ; Immunotherapy, Adoptive/adverse effects* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Cell- and Tissue-Based Therapy ; Antigens, CD19/adverse effects*

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

Objective:To investigate the efficacy of plasma exchange (PE) in treatment of patients with acute respiratory distress syndrome (ARDS).Methods:Forty-two patients who met the inclusion criteria in the intensive care unit of Chenzhou First People′s Hospital were randomly divided into control group and plasma exchange (PE) group with 21 cases in each group. The control group received conventional treatment; while the PE group received conventional treatment plus PE. The mechanical ventilation time (MVT), length of ICU stay (ICU LOS), 28-day mortality and 90-day mortality of patients were analyzed. The oxygenation index, SOFA score, norepinephrine (NE) dose, C-reactive protein (CRP), procalcitonin (PCT) and IL-6 levels were evaluated before and after treatment.Results:In the control group the oxygenation index, IL-6, PCT and CRP were significantly improved after treatment ( t=-4.50, 2.46, Z=-3.53, t=5.55, all P<0.05), but the SOFA score and NE dose were not significantly changed ( t=1.98, Z=-0.47,all P>0.05). In the PE group, the oxygenation index, SOFA score, IL-6, PCT, CRP were significantly improved and the NE dose was reduced after treatment ( t=2.18, 9.23, 5.26, Z=-3.77, t=7.27 and Z=-2.54,all P<0.05). The oxygenation index, SOFA score, IL-6, CRP were significantly better after treatment and NE dose was lower in PE group than those in the control group ( t=2.18, -2.21, -2.12, -2.61 and Z=-2.11, all P<0.05). Compared with the control group, the MVT(14.0±5.2d vs. 18.4±6.3d), ICU LOS(19.3±4.9d vs. 23.2±7.3d) and 28-day mortality (14.3%(3/21) vs. 42.8%(10/21)) in the PE group were significantly decreased ( t=-2.48, -2.04 and χ2=4.20,all P<0.05). There was no significant difference in the 90-d mortality between the two groups (28.6%(6/21) vs. 52.4%(11/21), χ2=2.47, P=0.208). Conclusion:Therapeutic plasma exchange can significantly reduce the inflammatory response, improve the organ function and reduce the short-term mortality of ARDS patients.

OBJECTIVE: Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. METHODS: A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. RESULTS: We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs. CONCLUSION This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.
Humans ; Hong Kong ; Integrative Medicine ; Critical Pathways ; China ; Constipation/therapy*

Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.