Objective To investigate the industrial and job changes among fishermen and their impact on economic incomes and schistosomiasis control following fishing ban and withdrawal in Poyang Lake areas, so as to provide insights into formulation of the schistosomiasis control strategy in these areas. Methods One township was selected as the study area from each of Duchang County, Poyang County and Yugan County around the Poyang Lake areas from May to June, 2023, and at least 500 fishermen at ages of 60 years and less were sampled from each township. Questionnaires were allocated to all subjects via the “Questionnaire Star” platform, including demographics, ratio of profits from different production activities before and after fishing ban and withdrawal, contact with infested water before and after fishing ban and withdrawal, and changes in household economic income before and after fishing ban and withdrawal. Subjects’ schistosomiasis examination and treatment data, and development of schistosomiasis hepatic fibrosis and advanced schistosomiasis were collected from 2016 to 2023. The changes in economic incomes, contact with infested water, sero-prevalence of human schistosomiasis, and proportions of schistosomiasis examinations and treatments were compared among study subjects. Results A total of 2 449 fishermen with an average age of (49.55 ± 8.86) years were investigated, including 1 654 full-time fishermen (67.54%) and 795 part-time fishermen (32.46%). The ratios of profits from fishing activities reduced from 88.15% and 34.82% before fishing ban and withdrawal to < 0.01% and 0.03% after fishing ban and withdrawal among full-time and part-time fishermen, while the ratios of profits from other production activities increased. The proportion of full-time fishermen who thought a reduction or a large reduction in their economic incomes was 79.93% (1 322/1 654), which was higher than that (66.79%, 531/795) of part-time fishermen (χ² = 50. 307, P < 0.001), and the proportion of part-time fishermen who thought minor changes in their economic incomes was 15.60% (124/795), which was higher than that (4.11%, 68/1 654) of full-time fishermen (χ² = 96.274, P < 0.001). There was a reduction in the contact with infested water among fishermen following fishing ban and withdrawal, and the proportions of respondents that had no contact, a large reduction in contact and a reduction in contact with infested water were 14.74% (361/2 449), 57.78% (1 415/2 449) and 26.05% (638/2 449), respectively. In addition, the sero-prevalence of schistosomiasis, and proportions of schistosomiasis examinations and treatments decreased from 9.79%, 87.14%, and 97.80% in 2016 to 4.38%, 53.16%, and 71. 51% in 2023 among fishermen in Duchang County, Poyang County and Yugan County (χ² = 6.944, 865.194, 238.953, all P values < 0.01), and the prevalence of schistosomiasis liver fibrosis and advanced schistosomiasis was 42.64% (826/1 937) and 6.08% (149/2 449) among study subjects, respectively. Conclusions Industrial and job changes among fishermen are beneficial for schistosomiasis control after fishing ban and withdrawal in Poyang Lake areas; however, there is an increased difficulty for management of fishermen due to an increase in number of migrant labors and other factors.

ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction （SQDHD） on diabetic kidney disease （DKD）， with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group （n=10） and a modeling group （n=50）， with 43 mice successfully modeled. The successfully modeled mice were further allocated into model， low-， medium-， and high-dose （4.68， 9.36， and 18.72 g·kg^-1， respectively） SQDHD， and dapagliflozin （0.13 mg·kg^-1） groups. The drug treatment groups were administrated with corresponding agents by gavage， and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip， respectively. Serum creatinine （Scr） and blood urea nitrogen （BUN） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff （PAS） staining. The fluorescence intensity of reactive oxygen species （ROS） in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions （Fe²⁺） and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 （GPX4） and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter （xCT）， as well as the arachidonic acid metabolic pathway-related proteins， including ACSL4， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins， including solute carrier family 7 member 11 （SLC7A11） and GPX4， as well as arachidonic acid metabolism-related factors （ACSL4， LPCAT3， and ALOX15） in the renal tissue. ResultsCompared with the normal group， DKD model mice exhibited a decrease in body weight （P<0.01）， increases in levels of blood glucose （P<0.01）， 24-hour urinary protein， Scr， and BUN （P<0.01）， along with severe pathological changes， such as mesangial cell proliferation， basement membrane thickening， tubular atrophy， and interstitial inflammatory cell infiltration. In addition， the modeling elevated the levels of Fe²⁺， MDA， LPO， and ROS （P<0.01）， lowered the GPX4 and xCT levels （P<0.01）， raised the ACSL4， LPCAT3， and ALOX15 levels （P<0.01）， down-regulated the mRNA levels of GPX4 and SLC7A11 （P<0.01）， and up-regulated the mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01） in the renal tissue. Compared with the model group， low-， medium-， and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight （P<0.01）， decreases in levels of blood glucose （P<0.01）， 24-hour urinary protein， and Scr （P<0.01）， alleviated pathological changes in glomeruli and tubules， and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe²⁺， MDA， LPO， and ROS levels （P<0.01）. The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT （P<0.01）， decreased levels of ACSL4， LPCAT3， and ALOX15 （P<0.05， P<0.01）， and down-regulated mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01）. ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels， inhibiting lipid peroxidation， up-regulating GPX4 expression， and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.

ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction （SQDHD） on diabetic kidney disease （DKD）， with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group （n=10） and a modeling group （n=50）， with 43 mice successfully modeled. The successfully modeled mice were further allocated into model， low-， medium-， and high-dose （4.68， 9.36， and 18.72 g·kg^-1， respectively） SQDHD， and dapagliflozin （0.13 mg·kg^-1） groups. The drug treatment groups were administrated with corresponding agents by gavage， and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip， respectively. Serum creatinine （Scr） and blood urea nitrogen （BUN） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff （PAS） staining. The fluorescence intensity of reactive oxygen species （ROS） in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions （Fe²⁺） and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 （GPX4） and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter （xCT）， as well as the arachidonic acid metabolic pathway-related proteins， including ACSL4， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins， including solute carrier family 7 member 11 （SLC7A11） and GPX4， as well as arachidonic acid metabolism-related factors （ACSL4， LPCAT3， and ALOX15） in the renal tissue. ResultsCompared with the normal group， DKD model mice exhibited a decrease in body weight （P<0.01）， increases in levels of blood glucose （P<0.01）， 24-hour urinary protein， Scr， and BUN （P<0.01）， along with severe pathological changes， such as mesangial cell proliferation， basement membrane thickening， tubular atrophy， and interstitial inflammatory cell infiltration. In addition， the modeling elevated the levels of Fe²⁺， MDA， LPO， and ROS （P<0.01）， lowered the GPX4 and xCT levels （P<0.01）， raised the ACSL4， LPCAT3， and ALOX15 levels （P<0.01）， down-regulated the mRNA levels of GPX4 and SLC7A11 （P<0.01）， and up-regulated the mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01） in the renal tissue. Compared with the model group， low-， medium-， and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight （P<0.01）， decreases in levels of blood glucose （P<0.01）， 24-hour urinary protein， and Scr （P<0.01）， alleviated pathological changes in glomeruli and tubules， and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe²⁺， MDA， LPO， and ROS levels （P<0.01）. The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT （P<0.01）， decreased levels of ACSL4， LPCAT3， and ALOX15 （P<0.05， P<0.01）， and down-regulated mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01）. ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels， inhibiting lipid peroxidation， up-regulating GPX4 expression， and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.

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.

Objective To explore the effect of health education based on interactive 3D-modeling of intracranial artery on interventional diagnosis and treatment for patients with intracranial artery stenosis.Methods A total of 70 patients requiring interventional diagnosis and treatment due to intracranial artery stenosis admitted to our department in 2022 were enrolled,and randomly divided into observation group and control group,with 35 cases in each group.Their stenotic sites of intracranial arteries included the vertebral and middle cerebral arteries.The observation group received the preoperative conventional education mode combined with interactive 3D-modeling to carry out health education,while the control group got the unified education sheet and slides to carry out routine preoperative health education.A self-made publicity and education effectiveness rating scale was used to score before and after the publicity and education,and their scores of awareness of intracranial artery stenosis,awareness of treatment plans,and satisfaction with medical treatment were compared between the 2 groups.Results Before the health education,there was no statistical differences in their awareness scores concerning intracranial vessels(normal intracranial arteries,intracranial arterial occlusion,and vascular stenosis treatment)between the 2 groups patients.After the implementation of education,the awareness scores of intracranial vessels were elevated in both groups,but the awareness scores of the normal intracranial artery,intracranial artery occlusion,vascular stenosis treatment,and treatment satisfaction were significantly higher in the observation group than the control group(P＜0.05).Moreover,the patients with middle cerebral artery and vertebral artery stenosis from the observation group obtained obviously higher propaganda score than those from the control group(P＜0.05).Conclusion The health education model combined with 3D-modeling can improve the patient's awareness of the diagnosis and treatment of intracranial artery stenosis,promote their satisfaction of medical treatment,and thus increase their compliance and the rate of interventional diagnosis and treatment,and then finally,prevent strokes caused by intracranial artery stenosis.

Objective To investigate the effect of anti-angiogenic drug Sitravatinib combined with poly(adenosine diphosphate[ADP]-ribose)polymerase inhibitor(PARPi)Niraparib on mucosal melanoma cell lines and its possible mechanism.Methods The CCK8 assay was used to detect the maximal half inhibitory concentration(IC50)of Sitravatinib and Niraparib targeting at mucosal melanoma(MM)cell lines.CompuSyn was used to detect the Combination Index(CI)in different concentrations of the two drugs.Flow cytometry was used to detect the effect of drugs on cell apoptosis.Colony formation assay was used to detect the effect of drugs on cell proliferation.Western blot was used to detect the protein expressions and RT-qPCR was used to detect mRNA expression.Results CI values was respectively 0.19 and 0.15 for Sitravatinib(2 μmol/L)in combination with Niraparib(20 μmol/L)in a human vaginal maligant melanoma cell line(HMVII)and a metastasis inguinal lymph node of vulvar malignant melanoma cell line(GAK).Compared with the control group and single-drug groups,the cell proliferation of the combination group was significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).The cell apoptosis rate was signifi-cantly increased(P＜0.01 or P＜0.001).The protein and mRNA expression of apoptosis-related biomarkers signifi-cantly increased(P＜0.001);In addition,the protein and mRNA expression of cell autophagy biomarkers signifi-cantly increased(P＜0.01 or P＜0.001).The protein expression of DNA damage marker significantly increased.Moreover,compared with the control group,The expression of radiation sensitive protein 51(RAD51)recombinase in the Sitravatinib single-drug group and combination group significantly reduced.As the dose of Sitravatinib gradu-ally increased up to 2 μmol/L,the protein and mRNA expression of RAD51 both significantly reduced(P＜0.05 or P＜0.01),the mRNA expression of BRCA1 and BRCA2 also significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).Conclusions Sitravatinib combined with Niraparib inhibits the proliferation of mucosal melanoma cells,induces cell apoptosis and promotes autophagy.The mechanism is potentially related to the inhibition of ho-mology-dependent recombination repairs(HRR).

R-spondin2 (Rspo2) is a member of protein family RSPOs, which can be coupled to receptor 4/5 (leucine-rich repeat-containing g protein-coupled receptor 4/5, LGR4/5), cell surface transmembrane E3 ubiquitin ligase ZNRF3/RNF43 (zinc and ring finger 3/ring finger protein 43), heparan sulfate proteoglycan (heparan sulfate proteoglycans, HSPGs) and the IQ motif (IQ gap 1) containing GTP enzyme activating protein 1, regulating the Wnt/β-catenin signaling pathway, which is the most widely studied signaling pathway and directly related to basic bone biology. Any problem in this pathway may have an impact on bone regulation. In recent years, it has been found that Rspo2 can act on osteoblast, osteoclast and chondrocytes through Wnt/β-catenin, and take part in occureace and development of some bone diseases such as ossification of the posterior longitudinal ligament (OPLL), osteoarthritis (OA) and rheumatoid arthritis (RA), so the study of Rspo2 may become a new therapeutic direction for bone-related diseases. Based on the latest research progress, this paper reviews the structure and main functions of Rspo2, the mechanism of Rspo2 regulating Wnt/β-catenin signaling pathway and its influence on skeletal system, in order to provide new ideas and ways for the prevention and treatment of bone-related diseases.

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.