OBJECTIVE To evaluate the cost-utility of disitamab vedotin （DV） combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic urothelial carcinoma（UC） with human epidermal growth factor receptor 2 （HER2） expression from the perspective of China’s health-care system.METHODS A cost-utility analysis was performed. A three-state partitioned survival model was constructed based on the RC48-C016 trial with a 1-week cycle length. The long-term health benefits [quality-adjusted life years（QALYs）] and costs of disitamab vedotin combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic UC with HER2 expression were simulated. The simulation time horizon was set to 15 years， and the discount rate was 4.5%. The willingness-to-pay （WTP） threshold was defined as twice China’s per capita gross domestic product（GDP） in 2025 （199 330 yuan/QALY）. The incremental cost-effectiveness ratio （ICER） between the two groups was compared， and one-way sensitivity analysis and probabilistic sensitivity analysis were conducted.RESULTS Compared with platinum-containing chemotherapy regimen， the DV plus toripalimab regimen yielded an additional 1.01 QALYs with an incremental cost of 183 224.45 yuan， and the ICER was 181 728.15 yuan/QALY， which was below the WTP threshold. At the current threshold， the probability that the DV combination regimen had a cost-utility advantage was 79.9%.CONCLUSIONS Taking twice China’s per capita GDP in 2025 as the WTP threshold， DV combined with toripalimab exhibits a cost-utility advantage over platinum-containing chemotherapy as first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma.

OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats.

OBJECTIVE To analyze the trends of potentially inappropriate medication （PIM） among elderly cancer patients in the context of the diagnosis-related groups（DRG）-based medical insurance payment reform.METHODS Relevant data were extracted for elderly inpatients with cancer at a Grade-A Level-Ⅲ hospital from January 2018 to March 2025. Prescribed medications were screened for PIM using the 2024 Chinese Criteria for Identifying PIM in the Elderly and the US 2023 Beers Criteria， and consistency was evaluated. An interrupted time-series （ITS） model was established， with the period from January 2018 to December 2020 designated as the pre-implementation group， and January 2021 to March 2025 as the post-implementation group. The study analyzed the impact of the medical insurance DRG payment reform on per capita hospitalization costs， per capita length of stay， average number of medication specifications per patient， overall PIM incidence， and PIM incidences for target medications among elderly cancer inpatients. To eliminate the influence of baseline characteristics （age， sex）， propensity score matching（PSM） was further applied， followed by an ITS model analysis to assess the impact of the DRG payment reform on the overall PIM incidence among elderly cancer inpatients.RESULTS A total of 16 910 elderly cancer inpatients were included （6 552 in the pre-implementation group， and 10 358 in the post-implementation group）； PIMs occurred in 9 138 patients， with an incidence of 54.04%. PIMs involved 198 types of medications， among which six target medications （including Diclofenac sodium enteric capsules and Oxycodone hydrochloride sustained-release tablets）， exhibited a higher average PIM incidence or a significant trend change； the Kappa value for the consistency evaluation of the assessments by two pharmacists was 0.931 （ P ＜0.001） . After the implementation of DRG， the per capita hospitalization costs showed a downward trend of 103.501 yuan per month （ P ＜0.001）； the per capita length of stay showed a slight upward trend （increasing by 0.052 days per month， P ＝0.017）， but the actual slope （－0.036） was less than 0； there was no significant change in the average number of medication specifications per patient （ P ＝0.193）. The DRG payment reform under medical insurance can produce statistically significant instantaneous impact effects on the PIM incidences among users of Diclofenac sodium enteric capsules， Doxofylline injection， and Cimetidine injection （ P values of 0.041， 0.001， and 0.036， respectively）， a statistically significant long-term trend effect on the PIM incidences among users of Oxycodone hydrochloride sustained-release tablets （ P ＝0.008）， and statistically significant instantaneous shock and long-term trend effects on the PIM incidences among users of Spironolactone tablets （ P values of 0.035 and 0.031） and Aminophylline injection （ P values of 0.009 and 0.031）. Regardless of whether PSM was applied， the overall PIM incidence among patients showed a slight upward trend [an increase of 0.228% per month， P ＝0.001 （without PSM）， or an increase of 0.239% per month， P ＜0.001 （after PSM）].CONCLUSIONS Following the implementation of the DRG payment reform for medical insurance， the per capita hospitalization cost for elderly inpatients with cancer decreases significantly， while the decline in the per capita length of stay slows. The overall PIM incidence shows a slight upward trend， and the trends in PIM incidence vary across different drug formulations.

OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.

[Purpose]To analyze the incidence trend and age,period,cohort effects of brain and other central nervous system tumors(brain tumor)in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of brain tumor from 1972 to 2021 were collected from the Qidong cancer registry database.The crude incidence rate(CR),age-standardized rate by Chi-nese standard population(ASRC),age-standardized rate by world standard population(ASRW)and average annual percentage change(AAPC)were calculated.The age-period-cohort(APC)model was used to analyze the age,period,and cohort effects of brain tumor incidence in Qidong City from 1972 to 2021.[Results]A total of 2 801 cases of brain tumor occurred in Qidong City from 1972 to 2021,including 1 475 male cases and 1 326 female cases.From 1972-1976 to 2017-2021,the CR increased from 1.81/10 5 to 9.28/10 5,the ASRC increased from 2.07/10 5 to 4.96/10 5,and ASRW increased from 2.00/105 to 4.98/105.From 1972 to 2021 the AAPC of CR,ASRC and ASRW were 3.97％(3.53％for male and 4.37％for female),2.02％(1.66％for male and 2.24％for female)and 2.06％(1.63％for male and 2.24％for female)(all P＜0.001).The Wald's Chi-square test of the APC model showed that there were significant differences in the trends of age,period and birth cohort effect of brain tumor risk(all P＜0.05).The age effect showed that the incidence of brain tumor increased with age,starting from the age group of 45～49 years old and reaching a peak of 25.84/10 5 in age group of 75～79 years old(95％CI:21.17/10 5～31.53/10 5).The period ef-fect showed that the risk of recent period was higher than that in the early period using 1992-1996 period as the reference,reaching the highest in 2012-2016(RR=1.64,95％CI:1.38～1.95).The birth cohort effect showed that the highest risk was in 2017-2021 births cohort(RR=11.17,95％CI:4.26～29.26)using 1952-1956 birth cohort as the reference.[Conclusion]The incidence of brain tumor in Qidong City has been rising;and age,period and cohort are the main influencing factors,suggesting that the middle-aged and elderly population should be the focus of brain tumor prevention and control.

[Purpose]To analyze the trends of cervical cancer incidence in Qidong City of Jiangsu Province from 1977 to 2021.[Methods]Based on the cervical cancer registration database in Qi-dong City from 1977 to 2021,the crude incidence rate,the age-standardized rate by the standard Chinese standard population and the world standard population(ASRC and ASRW),the truncated rate of 35～64 years old,the cumulative rate of 0～74 years old,and the cumulative risk were cal-culated;the incidence rates of birth cohorts were analyzed.Joinpoint regression analysis was per-formed with Joinpoint 4.9.0.0 software to calculate the annual percentage change(APC)and the average annual percentage change(AAPC)of cervical cancer incidence.[Results]A total of 2 253 new cases of cervical cancer registered in Qidong City from 1977 to 2021,accounting for 1.62％of the total case numbers of cancer in the whole population,and for 4.03％of the total number of cancers in women.The crude incidence rate was 8.75/105,the ASRC was 4.54/105,the ASRW was 6.01/105,the truncated rate(35～64 years old)was 15.09/105,the cumulative rate(0～74 years old)was 0.63％,and the cumulative risk was 0.63％.The incidence of cervical cancer increased with age from 1977 to 2021.The average incident age was 55.36 years old,with the lowest age of 47.51 years old in 2010.Secular trend analysis showed that the AAPC of the crude incidence of cervical cancer was 6.010％(95％CI:4.951％～7.081％)(P＜0.001),among which the trend decreased from 1977 to 1999,with an APC of-2.507％;and then the trend increased from 1999 to 2017,with an APC of 14.436％(P＜0.001).The rising and falling trend curves of the AS-RC and ASRW were similar to that of the crude incidence.The age group and time period analysis showed that the peak incidence was in the older age groups before 2006,while the peak inci-dence appeared in the age groups of 45～54 years old from 2007 to 2021.The AAPCs in age groups of 25～64 years old demonstrated upward trends(all P＜0.05).The birth cohort analysis showed that the cervical cancer incidence in the 1937-1941 birth cohort was the lowest,and the birth cohort-specific rates in all age groups showed"V-shape"trends.[Conclusion]Long-term monitoring of cervical cancer incidence in Qidong has shown a trend of initially slow decline fol-lowed by a rapid increase,with the peak incident shifting towards younger ages.The rising trends of cervical cancer incidence in last two decades may be associated with the increased HPV infection,suggesting that measures to reduce HPV infection and enhance vaccination should be strengthened.

OBJECTIVE: To establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer. METHODS: Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed. RESULTS: Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer. CONCLUSION In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis ; Humans ; Tooth, Deciduous ; Cone-Beam Computed Tomography ; Space Maintenance, Orthodontic/methods* ; Imaging, Three-Dimensional ; Orthodontic Wires ; Dental Stress Analysis ; Mandible ; Stress, Mechanical

Phantom limb pain (PLP) is a form of neuropathic pain occurring after limb amputation, and its underlying mechanisms remain unclear, posing significant challenges for clinical management. Spinal cord stimulation (SCS), a neuromodulation technique, has shown potential in relieving chronic pain, though its long-term efficacy and safety in treating PLP require further validation. This report presents a case of a 42-year-old male experiencing persistent radiating, lightning-like pain [Visual Analog Scale (VAS) score 8-9], following right upper limb amputation. Preoperative imaging revealed signal loss in the right nerve roots at C₆-T₁. A percutaneous electrode was implanted surgically to achieve full coverage of the painful region. Five days postoperatively, the VAS score dropped to 2-3, and after 1 year of follow-up, the patient continued to experience significant pain relief (VAS 1-2), with complete resolution of depressive symptoms and cessation of analgesic medication. Existing studies suggest that the long-term outcomes of SCS may fluctuate, and attention should be paid to potential complications such as infection and electrode displacement.
Humans ; Phantom Limb/therapy* ; Male ; Adult ; Spinal Cord Stimulation/methods* ; Electrodes, Implanted ; Amputation, Surgical/adverse effects*

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.