Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective:To investigate the clinical features of patients with maintenance hemodialysis (MHD) infected with SARS-CoV-2 and analyze the risk factors of death after SARS-CoV-2 infection, and to provide clinical data for early detection of critically ill patients and timely intervention.Methods:It was a cross-sectional investigation study. MHD patients in the hemodialysis centers of four tertiary hospitals with geographical representation in Shanxi province from December 1, 2022 to January 31, 2023 were enrolled, and the demographic data, dialysis-related indicators, laboratory test results and clinical features of SARS-CoV-2 infection were collected by distributing the questionnaires on SARS-CoV-2 infection, and consulting the hospital medical record system and the outpatient hemodialysis information system. SARS-CoV-2-infected patients were divided into survival group and death group according to whether all-cause death occurred and the differences of baseline data between the two groups were compared. Multivariate logistic regression analysis method was used to analyze the risk factors of mortality in MHD patients infected with SARS-CoV-2.Results:A total of 519 MHD patients were included in this study, with 508 patients (97.88%) infected with SARS-CoV-2, 474 patients in the survival group and 34 patients in the death group. The clinical symptoms of MHD patients infected with SARS-CoV-2 were diverse, and the most common initial symptom was fever (314/508, 61.81%). Other initial symptoms included cough and phlegm in 66 patients (12.99%), fatigue in 66 patients (12.99%), poor appetite in 20 patients (3.94%), dyspnea in 20 patients (3.94%), muscle pain in 14 patients (2.76%) and diarrhea in 8 patients (1.57%). Compared with the survival group, the death group had older age ( t=5.229, P<0.001), high proportions of males ( χ2=12.319, P<0.001) and diabetic nephropathy ( χ2=49.423, P<0.001), and lower levels of red blood cells ( t=-5.060, P<0.001), lymphocyte ( t=-2.614, P=0.011), neutrophil ( t=-5.117, P<0.001), serum albumin ( t=-2.940, P=0.012), serum prealbumin ( t=-3.519, P=0.001), blood phosphorus ( t=-3.309, P=0.002), serum creatinine ( Z=-3.607, P<0.001), total triglyceride ( Z=-2.486, P=0.013), total cholesterol ( Z=-3.291, P=0.001) and low-density lipoprotein cholesterol ( Z=-3.292, P=0.001). Among 508 SARS-CoV-2-infected patients, 194 patients (38.19%) were treated with nonsteroidal anti-inflammatory agents, 154 patients (30.31%) were treated with antibiotics, and 98 patients (19.29%) were treated with antiviral drugs. There were 225 (43.29%) vaccinated patients against SARS-CoV-2. Multivariate logistic regression analysis showed that low red blood cells ( OR=0.256, 95% CI 0.014-0.429), low lymphocytes ( OR=0.487, 95% CI 0.193-0.826), low serum albumin ( OR=0.613, 95% CI 0.329-0.917), older age ( OR=1.227, 95% CI 1.066-1.412) and diabetes mellitus ( OR=1.126, 95% CI 1.025-1.235) were the independent influencing factors of all-cause mortality in MHD patients infected with SARS-CoV-2. Conclusions:The clinical manifestations of SARS-CoV-2 infection in MHD patients are varied. Low red blood cells, low lymphocytes, low serum albumin, elder age and diabetes mellitus are the independent risk factors of death after SARS-CoV-2 infection in MHD patients. Strengthening management of MHD patients especially in the elderly, and improving and correcting anemia and malnutrition in time, may reduce the death risk of SARS-CoV-2 infection in MHD patients.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

A new Schiff base modified MCM-41 molecular sieve(N-MCM-41)was synthesized via post-grafting method with 2-pyridine formaldehyde for efficient removal of lead ions(Pb2+)from aqueous solution.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier transform-infrared(FT-IR)spectroscopy,thermogravimetric analysis(TGA),and X-ray photoelectron spectroscopy(XPS)were employed to characterize the structure,morphology,surface functional groups and chemical states of N-MCM-41.Moreover,the adsorption behavior of Pb2+by N-MCM-41 was systematically studied.Batch adsorption studies revealed that N-MCM-41 showed the maximal adsorption capacity of 101.3 mg/g at 45℃and pH=5.5 under the initial Pb2+ concentration of 80 mg/L after 180 min adsorption.The adsorption process conformed to the Langmuir isotherm model and the pseudo-second-order kinetics model.The adsorption of Pb2+by N-MCM-41 was a spontaneous and endothermic process.Adsorption mechanism analyses suggested that functional groups on N-MCM-41 had strong coordination ability with Pb2+to improve the adsorption capacity.The synthesized N-MCM-41 adsorbent exhibited excellent reusability in five regeneration cycles.Overall,this study showed that the N-MCM-41 had good application prospect to remove Pb2+ from aqueous solution.

This paper summarized the clinical experience of using the method of “returning fire to its origin” for treatment of paroxysmal sympathetic hyperactivity （PSH）. According to the causes and clinical characteristics of PSH， the author believes that the deficiency of kidney qi， and the loss of yin and yang are the basis of the pathogenesis of PSH. Fright causes qi to be chaotic as the triggering mechanism of PSH. The key mechanism of PSH is that the deficiency yang with upper manifestation， and the fire does not return to its origin. The treatment should be nourishing yin and astringing yang， by taking modified Yinhuo Decoction （引火汤） internally， and receiving warm moxibustion as the first choice externally with selected acupoints Guanyuan （CV 4）， Mingmen （GV 4）， and bilateral Yongquan （KI 1）； For prevention， attention should be paid to take care of stomach qi， support healthy qi， and cultivate original qi.

Objective:To explore the application of a role transition shock model based on the teach-back technique in knee arthroplasty nursing teaching.Methods:We assigned 50 nursing student interns practicing in the knee arthroplasty team of Orthopedics Department of Nanjing First Hospital between August 2020 and August 2022 into control group ( n=25, traditional teaching) and observation group ( n=25, teach-back-based role transition shock model teaching) according to the order of admission. At the end of internship, the examination scores, the impact of transition shock on comprehensive abilities, and teaching satisfaction of the students were assessed and analyzed using the t test and Fisher's exact test with the use of SPSS 22.0. Results:Compared with the control group, the observation group scored significantly lower in the physical, psychological, knowledge and skills, and sociocultural and developmental dimensions of the transition shock assessment scale ( P<0.05). The observation group showed significantly higher scores of nurse-patient communication, nursing practice, disease observation, health education, humanistic care, team cooperation, clinical thinking, and emergency response than the control group ( P<0.05). The examination results of the observation group were significantly better than those of the control group ( t=12.31, 11.52, P<0.001). The teaching satisfaction rate of the observation group was significantly higher than that of the control group [100.00% (25/25) vs. 68.00% (17/25), χ2=9.52, P=0.002]. Conclusions:The teach-back-based role transition shock model can help alleviate the transition impact faced by nursing student interns when entering clinical practice, and also improve their comprehensive abilities as well as satisfaction with teaching.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

Objective To objectively evaluate the clinical efficacy and safety of acupuncture in regulating the mood of patients with post-stroke depression(PSD)and explore the possible target of acupuncture intervention.Methods 76 patients with PSD were randomly divided into treatment group and control group.The control group was treated with routine treatment measures for stroke,and the treatment group was treated with acupuncture on this basis.The main acupoints were Shangxing,Baihui,Shenting,Fengchi and Dugu,supplemented by acupuncture on Taichong,Hegu,Quchi,Neiguan,Yanglingquan,Zusanli and Taixi,5 times a week,continuously treated for 4 weeks,followed up on the 90th day after treatment.The levels of serum 5-hydroxytryptamine,norepinephrine and intestinal microflora before and after treatment were compared with the 17 Hamilton Depression Scale scores(HAMD),modified Barthel Index(MBI),and the levels of serum 5-hydroxytryptamine and norepinephrine before and after treatment.Results The HAMD score and MBI index of the two groups after treatment and follow-up were lower than those before treatment.The levels of 5-hydroxytryptamine and norepinephrine in the treatment group after treatment were higher than those before treatment(P<0.01),and significantly higher than those in the control group(P<0.01).After acupuncture,the dominant bacterial groups of Bacteroides,Thick-wall bacteria and Broughter bacteria in patients showed an upward trend(P>0.05).The difference of bacteria before and after treatment was mainly concentrated in signal pathways such as ECM-receptor interaction,and the difference was statistically significant(P<0.01).Conclusion Acupuncture can help patients improve their ability of daily living,and also improve the relative abundance of intestinal flora in PSD patients to a certain extent,so as to regulate the levels of 5-HT and NE to relieve the depression of patients,which is worthy of promotion in clinical practice.