Curcuma zedoaria (commonly known as "E Zhu" in traditional Chinese medicine) is a perennial herb, and its rhizome is used for medical purpose. It is clinically effective for treating various symptoms caused by blood stasis. For oral administration, E Zhu is often combinded with other traditional Chinese medicines to prepare various formulations such as decoctions, pills, and tablets. This allows its medicinal properties to reach the internal organs and meridians, promotes the flow of qi and blood, and dissipates stasis and stagnation. E Zhu is mainly distributed in Guangxi, Sichuan, Zhejiang, Yunnan, and other regions in China. However, cadmium (Cd) contamination has emerged in multiple areas due to the development of battery, smelting, electroplating, and chemical industries. Additionally, the intrinsic Cd-accumulation property of E Zhu coupled with the Cd pollution has rendered a prominent issue during its cultivation and medicinal application, thereby comprimising the safety and efficacy of its clinical use. This paper comprehensively reviewed the absorption and accumulation patterns of Cd in E Zhu and proposed a comprehensive chain of control measures from cultivation to processing and purification, aiming to reduce Cd in E Zhu. These measures are expected to lower the potential risk of low-dose Cd accumulation in the human body and further ensure the safe clinical application of E Zhu as a raw material in traditional Chinese medicine.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Background and purpose:China is a country with high incidence rate and mortality of liver cancer.In 2022,there were approximately 368 000 cases of liver cancer and 317 000 deaths in China.Extending the survival period of liver cancer patients is an urgent issue that we need to address.In recent years,tyrosine kinase inhibitor(TKI)alone or in combination with immune checkpoint inhibitors have achieved good results in the treatment of primary liver cancer.However,most studies did not include the combination of transcatheter arterial chemoembolization(TACE)treatment.We speculate that combining TKI drugs with immune checkpoint inhibitors and TACE therapy may provide greater benefits to liver cancer patients.Therefore,this study aimed to evaluate the short-term efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of liver cancer.Methods:This study is a single arm phase Ⅱ clinical trial approved by the ethics committee of The Third People's Hospital of Yibin(ethical approval numbers:2022009).Inclusion criteria:① Age 18-70 years;② Primary liver cancer confirmed by clinical diagnosis or histopathology;③ Eastern Cooperative Oncology Group(ECOG)performance status score of 0-1;④ China Liver Cancer Staging(CNLC)stage Ⅱb-Ⅲb;⑤ Adequate cardiopulmonary function;⑥ Child-Pugh score≤8 points;⑦ At least one measurable tumor lesion according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)version 1.1.From November 1,2021 to March 1,2024,we recruited 61 patients,of whom 39 met the criteria.Firstly,all enrolled patients received TACE treatment.Approximately one week after the initial TACE procedure,12 mg of anlotinib(adjusted according to tolerance)was administered orally on days 1-14,every 3 weeks;Simultaneously 200 mg of sintilimab was administered intravenously on day 1,every 3 weeks.After completing 2 cycles of treatment,efficacy evaluation was conducted according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)1.1.The primary observation indicators of the study were objective response rate(ORR),and the secondary observation indicators were median progression-free survival(mPFS),disease control rate(DCR)and safety.Results:The ORR of this study was 76.9%,DCR was 94.9%,and mPFS was 9.2 months(95%CI:2.317-16.083).39 cases(100%)had grade 1-2 adverse reactions,15 cases(38.5%)had grade 3 adverse reactions,5 cases(12.8%)had grade 4 adverse reactions,and 1 patient died due to upper gastrointestinal bleeding.In the stage mainly treated with TACE combined with TKI and immunotherapy,the incidence of grade 3-4 adverse reactions was higher compared with the stage mainly treated with anlotinib combined with sintilimab.The vast majority of adverse reactions can be recovered through conventional treatment methods.Conclusion:TACE combined with anlotinib and sintilimab has a definite therapeutic effect and overall safety and controllability in the treatment of CNLC stage Ⅱb-Ⅲb liver cancer.This combination therapy may provide a new treatment model for CNLC stage Ⅱb-Ⅲb liver cancer patients.However,further exploration is needed to address the pain,vomiting,decreased appetite,liver function damage,upper gastrointestinal bleeding,and other issues caused by this treatment mode.

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.

Objective To explore the injury types,associated injuries,and correlations of the lateral meniscus posterior root(LMPR),and to improve the comprehensive understanding of LMPR and its associated injuries.Methods The patients with LMPR who underwent knee MRI examination were retrospectively selected.A total of 223 patients with LMPR injury were classified into 4 types.The integ-rity of the meniscofemoral ligament and the grading of the cartilage injuries in the lateral tibiofemoral compartment were recorded.The relationship between the types of LMPR injury and the lateral meniscus tear locations,as well as lateral meniscus extrusion were analyzed.The relationship between the integrity of the meniscofemoral ligament and lateral meniscus extrusion was analyzed.The correlation between the time to clinical presentation after injury and the grading of the cartilage injuries was analyzed in patients with anterior cruciate ligament(ACL)ruptures.Results The incidence of LMPR injury was 1.02％,with males affected 2.19 times more frequently than females.Among patients with ACL ruptures,the incidence was 13.17％.Both type Ⅰ and type Ⅱ LMPR inju-ries predominantly involved only the posterior root,while type Ⅲ injuries mainly affected the posterior root extending to the posterior horn and body.The incidence of the lateral meniscus extrusion was higher in type Ⅲ LMPR injury than in type Ⅱ.When the menis-cofemoral ligament was not intact,the incidence of the lateral meniscus extrusion increased.In patients with ACL ruptures,a longer time to clinical presentation after injury was associated with more severe cartilage injuries grading in the lateral tibiofemoral compart-ment.Conclusion Males are more susceptible to LMPR injuries than females.The classification of LMPR injuries is correlated with the location of the lateral meniscus tears and the incidence of the lateral meniscus extrusion.The integrity of the meniscofemoral lig-ament is related to the incidence of the lateral meniscus extrusion.The time to clinical presentation after injury is related to the sever-ity of cartilage injury in ACL rupture patients.

Objective To explore the ultrasonic cleaning effect and influencing factors of emergency laparoscopic surgical instruments at night.Methods A total of 698 emergency laparoscopic surgical instruments cleaned by ultrasound at night were selected as the research subjects,and the unqualified ultrasonic cleaning of instruments was statistically analyzed.Univariate and multivariate binary Logistic regression equations were used to analyze the factors that may lead to unqualified ultrasonic cleaning.Results Among 698 ultrasonic cleaning sessions for emergency laparoscopic surgical instruments at night,a total of 55 times(7.88%)were unqualified.The results of univariate and multivariate binary Logistic regression analysis showed that the time from cleaning to the end of surgery≥10 hours,luminal surgical instruments,nonstandard pretreatment,unqualified cleaning water quality,and unqualified cleaning medium were the risk factors that lead to the occurrence of unqualified ultrasonic cleaning of emergency laparoscopic surgical instruments at night(OR>1,P<0.05),while manual+ultrasonic cleaning was the protective factor to avoid the occurrence of unqualified ultrasonic cleaning of emergency laparoscopic surgical instruments at night(OR<1,P<0.05).Conclusion The unqualified rate of ultrasonic cleaning of emergency laparoscopic surgical instruments at night is relatively high,so it should be cleaned as early as possible after the surgery.Before ultrasonic cleaning,manual clean-ing should be carried out as much as possible,especially for luminal surgical instruments that are difficult to clean,standardized pretreatment should be carried out,and qualified cleaning water quality and medium should be selected.