OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Septic acute kidney injury (SAKI) is one of the most common complications of sepsis, and the occurrence of acute kidney injury (AKI) indicates that the patient's condition is critical with a poor prognosis. The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow, inadequate renal perfusion, inflammatory response, and microcirculatory dysfunction caused by sepsis, which subsequently leads to ischemia and necrosis of renal tubular cells. Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role. Autophagy is a programmed intracellular degradation process and is a form of programmed cell death. Cells degrade their cytoplasmic components via lysosomes, breaking down and recycling intracellular constituents to meet their metabolic needs, maintain intracellular homeostasis, and renew organelles. During SAKI, autophagy plays a crucial protective role through various mechanisms, including regulating inflammation and immune responses, clearing damaged organelles, and maintaining stability in the intracellular environment. In recent years, the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention. Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy [such as mammalian target of rapamycin (mTOR) signaling pathway, AMP-activated protein kinase (AMPK) signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and Sirtuins (SIRT), autophagy associated factor Beclin-1, and Toll-like receptor (TLR)] are involved in the development of SAKI. Due to the complex pathogenesis of SAKI, current treatment strategies include fluid management, infection control, maintenance of internal environment balance, and renal replacement therapy; however, the mortality remains high. In recent years, it has been found that autophagy plays a critical protective role in sepsis-mediated AKI. As a result, an increasing number of drugs are being developed to alleviate SAKI by regulating autophagy. This article reviews the latest advances in the role of autophagy in the pathogenesis and treatment of SAKI, with the aim of providing insights for the development of new drugs for SAKI patients.
Humans ; Acute Kidney Injury/etiology* ; Autophagy ; Sepsis/complications* ; Signal Transduction

Narrow leaf 1 (NAL1) plays an important role in plant branching, while little is known about the roles of this gene in petunias. In this study, PhNAL1b was cloned from Petunia×hybrida cv. Mitchell Diploid, with a total length of 1 767 bp, encoding a protein composed of 588 amino acid residues and containing the peptidase S64 domain. The PhNAL1b promoter region contained several elements involved in the responses to auxin, jasmonic acid, abscisic acid, and light. The expression analysis showed that PhNAL1b had the highest expression level in roots and the lowest expression level in flowers, and its transcription could be inhibited by decapitation and cytokinin. The subcellular localization analysis showed that PhNAL1b was located in the nucleus and was a nuclear protein. Virus-induced gene silencing was employed to downregulate the expression of PhNAL1b, which resulted in significant increases in branch number and plant height. The results indicated that PhNAL1b played an important role in regulating the branching of petunias. This study lays a foundation for revealing the mechanism of NAL1 in regulating branch development and provides genetic resources for plant architecture improvement.
Petunia/growth & development* ; Plant Proteins/metabolism* ; Diploidy ; Gene Expression Regulation, Plant ; Cloning, Molecular ; Promoter Regions, Genetic

Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment， liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this， this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis （ingredients such as ethanol extract of Euonymus alatus and paclitaxel， as well as compounds such as Ershiwuwei songshi pill and Ganfukang）， clear away heat and toxic material （ingredients such as betulinic acid， total flavonoids from Persicaria perfoliata， as well as compounds such as Pianzaihuang and Kehuang capsules）， and sooth the liver and promote qi circulation （ingredients such as fraxetin and cucurbitacin B， as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction） can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway， reducing inflammatory reactions， and inhibiting the proliferation of hepatic stellate cells.

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA). Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively). Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

Objective This paper focuses on the manufacturing technique of bubble microneedles and temperature-sensitive materials in order to design and prepare a temperature-sensitive reservoir microneedle.The objective is to evaluate the feasibility of addressing the issue of low drug load in traditional Chinese medicine(TCM)external preparations using microneedles.Methods The study involved the utilization of sinomenine hydrochloride as the model drug.The drug,along with the temperature-sensitive material N-isopropylacrylamide,was filled into the cavity of the bubble microneedle made from chitosan.Through positioning and curing processes,a temperature-sensitive sinomenine hydrochloride reservoir microneedle was prepared.The microneedle consisted of a needle body,a positioning layer,a basal layer,and a drug reservoir.The drug load,size,length,mechanical properties,and puncture ability of the prepared reservoir microneedle were measured to characterize and evaluate its drug load and mechanical properties.In addition,the in vitro release characteristics of the microneedles were determined using Franz diffusion cells,while the in vivo release characteristics were evaluated using the percutaneous microdialysis technique.Results The research result demonstrated that the prepared temperature-sensitive reservoir microneedle had a drug load of approximately 5.76 mg/cm2.The exposed needle tip had a conical shape with a height of around 650 μm,exhibiting good mechanical strength and skin puncture ability.The in vitro release tests showed that the microneedle could simulate the temperature of the skin and release the drug in a controlled and gradual manner,displaying characteristics of diffusion and dissolution of the skeleton.Furthermore,compared to conventional external preparations,the reservoir microneedles significantly enhanced transdermal permeation of the drug in the in vivo percutaneous studies.Conclusion The study demonstrated that reservoir-type microneedles prepared using temperature-sensitive materials and bubble microneedle preparation techniques could significantly increase the drug load of microneedles,providing the advantage of microinvasion.

Objective:To explore the HIV-1 drug resistance in patients with HIV/AIDS in Guilin city following the failure of antiretroviral treatment (ART).Methods:Plasma samples were collected from patients in Guilin who had received ART for more than 1 year and had a HIV viral load greater than or equal to 1 000 copies/ml from January 2019 to December 2023, and demographic information was also collected for HIV-1 genotype subtype analysis and drug resistance testing to determine the resistance mutation loci and the susceptibility of the strains to drugs.Results:A total of 766 patient samples with failed ART collection and successful amplification were collected, of which 536 (69.97%, 536/766) were male, with an average age of 53 years; a total of 8 HIV-1 subtypes were detected, with CRF01_AE (80.55%, 617/766), CRF07_BC (11.10%, 85/766) and CRF08_BC (6.92%, 53/766) predominated. The drug resistance analysis showed that the HIV-1 drug resistance rate was 34.86% (267/766), including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitor (PI), with dual resistance to NRTIs/NNRTIs (48.31%, 129/267) and NNRTIs resistance (43.07%, 115/267) predominantly. A total of 37 resistance mutation sites were detected, 14 NRTIs-associated mutation sites mainly included M184V/I (47.57%, 127/267), K65R (18.73%, 50/267), K70E/N/T/G/R (13.11%, 35/267), etc., and 18 NNRTIs-associated mutation sites mainly included K103 N/R (56.93%, 152/267), V179 D/E/T (21.72%, 58/267), G190C/S/Q (17.23%, 46/267), and V106I/M (16.85%, 45/267), etc.; and 5 PIs-associated mutation sites was the highest with L10V/I mutation rate (3.00%, 8/267).Conclusions:HIV/AIDS patients in Guilin have shown favorable outcomes in antiviral therapy, with a relatively low overall incidence of drug resistance. However, it is essential to enhance surveillance to reduce the spread of drug-resistant strains in the future.

ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.