Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

Objective To analyze the incidence and mortality of gastric cancer in countries and territories with different human development index(HDI)levels in 2022,and to understand the burden of gastric cancer globally and in China.Methods Data on gastric cancer incidence and mortality were collected from GLOBOCAN 2022 and HDI data for all countries were obtained from the Human development report 2022.Spearman correlation was applied to examine the associations between the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),mortality-to-incidence ratio(M/I),and HDI for gastric cancer.The Wilcoxon rank-sum test was used to assess the differences in ASIR and ASMR between males and females.Results In 2022,gastric cancer ranked the 5th in both incidence and mortality among all cancer types globally.In China,gastric cancer ranked the 5th in incidence and the 3rd in mortality among all cancer types.The ASIR and ASMR of gastric cancer showed a descending trend from high,very high,medium to low HDI countries and territories.The ASIR of gastric cancer was positively correlated with HDI(rs=0.256,P=0.001),while ASMR showed no significant correlation with HDI(rs=-0.008,P=0.918).The M/I was negatively correlated with HDI(rs=-0.831,P＜0.001).The ASIR and ASMR of gastric cancer in males were significantly higher than those in females globally,in China,and across all HDI groups(all P＜0.05).Globally,both ASIR and ASMR of gastric cancer remained relatively stable before the age of 45,but showed a consistently rising trend after the age of 45.In China,the ASIR and ASMR of gastric cancer exceeded global average level across all age groups.Conclusion The burden of gastric cancer incidence and mortality is higher in very high and high HDI countries and territories compared to medium and low HDI countries and territories.In China,the burden of gastric cancer incidence and mortality is above the global average,highlighting the need for targeted prevention and control measures.

Objective To compare the incidence and mortality of brain and central nervous system(CNS)tumors in countries and territories with different human development index(HDI)in 2022,to make a comparison with the current epidemiological situation in China,and to assess the association between HDI and the incidence and mortality of brain and CNS tumors.Methods The data on brain and CNS tumors from GLOBOCAN 2022 were collected,and HDI data were organized based on the Human development report 2022.Generalized additive model(GAM)was used to analyze the relationships between standardized incidence ratio(SIR),standardized mortality ratio(SMR),mortality-to-incidence ratio(M/I),and HDI.Results The incidence and mortality of brain and CNS tumors increased with age in 2022,with a significant increasing trend in countries and territories with very high HDI.Countries and territories with high and very high HDI had more cases and more deaths,and countries and territories with very high HDI had the highest SIR and SMR.SIR for brain and CNS tumors in China was higher than the global average,while China's SMR was lower.M/I varied among countries and territories with different HDI,with lower M/I in countries and territories with high and very high HDI.HDI had a significant nonlinear effect on SIR(edf=1.740,P＜0.000 1)and M/I(edf=1.809,P＜0.000 1),and a significant linear effect on SMR(edf=1,P＜0.000 1).As HDI increased,SIR and SMR generally showed an increasing trend,while M/I showed a decreasing trend.Conclusion There are significant global differences in incidence and mortality of brain and CNS tumors in patients with different HDI in 2022;increasing HDI can reduce the risk of brain and CNS tumors and improve treatment outcomes,and prevention and control strategies should be made for different age groups and HDI.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

Malocclusion can be treated effectively with fixed orthodontic appliances,but it is difficult to maintain oral hygiene during orthodontic treatment.Dental plaque tends to accumulate on the tooth surface,which in turn results in enamel demineralization and white spot lesions due to the production of acid,causing aesthetic and health hazards to the patients.The prevention of white spot lesions in or-thodontic treatment needs to be addressed urgently.It is a hot topic in the research of orthodontic materials for the prevention of enamel demineralization and white spot lesions by adding different components in orthodontic adhesives.In this paper,the research progress of orthodontic adhesive modification in the prevention and treatment enamel white spot lesions is summarized.

Objective:To explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

The medical and health field has abundant multimode data and open and diverse medical health scenarios,which is one of the most promising fields for the application of artificial intelligence large models.Based on basic hardware,equipment,and model frameworks,the artificial intelligence model is pre-trained,fine-tuned,evaluated,optimised,and utilized through medical texts,medical images,or medical multimode datasets to complete model construction.The large medical and health model has been successfully applied in the fields of auxiliary diagnosis and treatment,medical imaging research,health management,biomedical research,drug research,medical examination and education,but it also faces challenges such as data security risks,moral and ethical risks,and technical risks.In order to regulate the development of artificial intelligence large model technology,some countries have formulated relevant laws,regulations,and standard guidelines.Opportunities and challenges coexist in the field of medical and health cooperation with artificial intelligence,and artificial intelligence large model technology still needs to be continuously optimised and developed to promote deeper integration with the medical and health field.

Robotics ; Robotic Surgical Procedures ; Kidney Transplantation

Objective:To investigate whether salidroside (SAL) improves lung tissue injury in rats with severe pneumonia (SP) through mediating toll-like receptor 4/nuclear transcription factor-κB/NOD-like receptor protein 3 (TLR4/NF-κB/NLRP3) signaling pathway.Methods:Seventy-five Wistar rats were used in this study. Fifteen of them were randomly selected as the sham operation group, and the others were induced by endotracheal infusion of Klebsiella pneumoniae ( Kp) suspension to construct a rat model of SP. After modeling, the rats were randomly divided into four groups with 15 rats in each group: model group, low-dose SAL group (30 mg/kg), high-dose SAL group (60 mg/kg) and dexamethasone (DXMS, 15 mg/kg) group. The sham operation group and the model group were given the same amount of normal saline for seven consecutive days. The wet-dry weight ratio (W/D) of lung tissues in each group was detected. HE and TUNEL staining methods were used to observe the morphology of lung tissues and cell apoptosis. The levels of TNF-α, IL-1β, IL-6, IL-18 and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The expression of TLR4, myeloid differentiation factor (MyD88), NF-κBp65, phosphorylated NF-κBp65 (p-NF-κBp65) and NLRP3 at protein level in lung tissues was detected by Western blot. Results:The rat model of SP was successfully constructed by endotracheal infusion of Kp suspension. Compared with the sham operation group, the model group showed more severe edema of lung tissues, increased W/D value ( P<0.05), loose and incomplete alveolar structure, edema of alveolar wall and thickened alveolar wall, massive inflammatory cell infiltration, increased apoptosis rate as well as higher levels of TNF-α, IL-1β, IL-6 and IL-18 and lower lover of IL-10 in BALF. Moreover, the relative expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues was increased in the model group ( P<0.05). Gradually improved pathological injury of lung tissues, decreased W/D value ( P<0.05), recovered alveolar structure, reduced alveolar wall edema and decreased cell apoptosis rate were observed in the low-dose and high-dose SAL groups as well as the DXMS group as compared with those of the model group. Besides, the three groups also showed decreased levels of TNF-α, IL-1β, IL-6 and IL-18 and increased level of IL-10 in BALF, and inhibited expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues ( P<0.05). DXMS performed better in improving lung injury in rats with SP, followed by high and low doses of SAL ( P<0.05). Conclusions:SAL could reduce cell apoptosis and improve the Kp-induced lung injury in rats. The mechanism might be related to the blockage of TLR4/NF-κB/NLRP3 signaling pathway activation and inhibition of inflammatory factor expression.