Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica（CMM）. Elucidating hygroscopic mechanisms plays a vital role in formulation design， process optimization， and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms， with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion， tailored to the physical properties of CMM extracts. In recent years， this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties， offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM， analyzes its advantages， disadvantages， and challenges in this domain， and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies， while also offering insights for its broader application in food and polymer materials.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

L-valine is an important branched-chain amino acid widely used in the food, pharmaceutical, and feed industries. Microbial fermentation has become the primary production method for L-valine. However, current industrial production still faces issues such as inefficient carbon flux utilization, imbalance in cofactor supply and demand, and suboptimal fermentation processes, which limit the efficient synthesis of L-valine. To further enhance the production performance of L-valine, In this study, metabolic engineering was conducted for a previously constructed Escherichia coli strain with a high yield of L-valine to optimize carbon flux distribution and balance cofactor consumption. Dual-phase oxygen-controlled fermentation was carried out to enhance L-valine production. Firstly, to address the pyruvate loss, we knocked out multiple competing pathway genes (ldhA, poxB, pflB, frdA, and pta), which resulted in a 48% increase in flask yield of the constructed strain VL-04. Next, we optimized the cofactor supply and demand balance by replacing ilvE with bcd (NADH-preferential) from Bacillus subtilis to construct the strain VL-06, which achieved a flask yield of 22.80 g/L, a further improvement of 25.8%. Subsequently, the fermentation conditions of VL-06 were optimized in a 5 L bioreactor with dual-phase oxygen-controlled fermentation. After optimization, the L-valine production reached 86.44 g/L in 26 h, with a glucose-to-acid conversion rate of 44.08% and a production intensity of 3.32 g/(L·h). This study not only shortens the time for L-valine production but also improves the economic efficiency, providing insights for similar fermentation processes employing dual-phase oxygen control.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Valine/biosynthesis* ; Fermentation ; Bacillus subtilis/genetics*

Analgesia is an important link in the treatment of severe patients after neurosurgery and plays a vital role in improving the prognosis of the patients.Understanding the status quo and influencing fac-tors of pain in severe patients after neurosurgery helps to predict the occurrence of pain,which is crucial for determining the new pain assessment methods and auxiliary analgesic methods and developing novel analgesic drugs.This paper reviews the pain status,pain evaluation and analgesic methods of severe patients after neuro-surgery in recent years so as to understand the pain management current status of the patients with severe neurological conditions and provide reference for the medical staff to implement the analgesic programs.

The goal of gastrointestinal endoscopy anesthesia management is to effectively calm and re-lieve pain while minimizing related adverse reactions and ensuring patient safety.Hypoxemia is the most com-mon adverse event during painless gastrointestinalendoscopy,and severe hypoxemia can cause cardiac and brain accidents.Therefore,how to prevent and reduce the occurrence of hypoxemia isa hot topic in clinical re-search.This article reviews the methods of preventing and reducing hypoxemia in general painless gastrointes-tinal endoscopy,and provides a reference for the selection of appropriate sedation and ventilation strategies for general painless gastrointestinal endoscopy anesthesia.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective To explore the feasibility and operability in identifying the therapeutic dominant stages of traditional Chinese medicine(TCM)based on subdivision model of disease course.Methods The hierarchical Bayesian model was used to differentiate the disease course of 125 cases of premature ovarian failure(POF),and the disease course of POF were divided into the occult stage,diminished ovarian reserve(DOR)stage,premature ovarian insufficiency(POI)stage,and POF stage.An then the paired sample t-test,Pearson correlation analysis and expert in-depth interview were used for the analysis of the therapeutic effects of TCM for POF at various stages.Results(1)Compared with POF stage,DOR and POI stages were frequently intervened by Chinese patent medicine.(2)In DOR(complicated with POI)stage and POF stage,there was significant difference between the degree of TCM intervention and the therapeutic effect(t =-3.70,P＜0.001).(3)The degree of TCM intervention was positively correlated with treatment outcomes in the DOR stage(r = 0.679,P＜0.001),so did in the POF stage(r = 0.432,P＜0.001),but the correlation in the POF stage was slightly lower than that in the DOR stage.(4)The results of in-depth interviews with experts of TCM gynecology showed that in the concealed phase of POF,the prognosis would be most favorable if TCM regulation and intervention were performed.In the DOR stage and POI stage,treatment with Chinese medicine prescriptions usually brought about better curative effect and prognosis.For the patients at POF stage,the therapeutic effect of TCM depended on the patients'compliance and the treatment course,and the effect was relatively not as good as that of the previous stages.Conclusion In the DOR stage and POF stage,the higher the degree of TCM intervention,the better the prognosis will be achieved for the patients treated with western medicine.In the POF stage,the efficacy of TCM intervention is reduced to a certain extent compared with the DOR stage.The results indicated that it is feasible and operable to identify the TCM therapeutic dominant stages based on the subdivision model of disease course.

Objective To investigate the effect of percutaneous endoscopic transforaminal discectomy(PETD)on L5-S1 lumbar disc herniation(LDH)and the influence of iliac crest height on the clinical efficacy.Methods A total of 86 patients treated with PETD for LDH(L5-S1 segment)from February 2019 to February 2018 were selected and grouped according to the relationship between the highest point of the iliac crest and the position of the L4-5 pedicle.Forty-eighty patients with the highest point of the iliac crest located below the upper edge of the L5 pedicle were included in group A;thirty-three patients with the highest point of the iliac crest located between the lower edge of the L4 pedicle and the upper edge of the L5 pedicle were included in group B,and five patients with the highest point of the iliac crest located above the lower edge of the L4 pedicle were included in group C.The operation indexes of the three groups were compared.The visual analogue score(VAS)and Oswestry Disability index(ODI)before and after surgery[preoperative(T0),1 week after surgery(T1),1 month,6 months and 12 months after surgery(T2,T3,T4)]were compared among the three groups.Results There was no difference in operation time and blood loss among the three groups(P>0.05).At T0,there was no difference in VAS score and ODI among the three groups(P>0.05).At T1-T4,when VAS score and ODI of the three groups were lower than that at T0,VAS in group A and B was lower than that in group C(P<0.05),but there was no difference between group A and B(P>0.05).Conclusion PETD has significantly clinical efficacy in the treatment of L5-S1 LDH,and whether the iliac crest height is higher than the level of the lower edge of the L4 pedicle will affect its clinical efficacy.

Objective To explore the distribution patterns of tongue and pulse manifestations and traditional Chinese medicine(TCM)syndrome elements in ischemic stroke(IS)patients of different genders and ages,thus to provide approaches for the prevention and treatment of stroke with TCM.Methods The criteria of six syndrome elements in Diagnostic Scale of Syndrome Elements in Ischemic Stroke were used for the comprehensive identification of syndrome elements in 5 254 cases of inpatients confirmed as IS at the first visit in Shenzhen Traditional Chinese Medicine Hospital from 2017 to 2023.Moreover,the tongue proper,tongue coating,and whose pulse manifestations ranking in the top five in terms of the frequency of occurrence were collected for comparison and analysis.Results(1)For the distribution of TCM syndrome elements in 5 254 cases of IS patients,phlegm-dampness syndrome was the most common syndrome type(3 544 cases,67.5%),and then came qi deficiency syndrome(653 cases,12.4%)and yin deficiency syndrome(453 cases,8.6%).There were statistically significant differences in the distribution of phlegm-dampness syndrome,internal heat syndrome,and yin deficiency syndrome between the male and the female(P＜0.01).And the distribution of phlegm-dampness syndrome,qi deficiency syndrome,internal wind syndrome,and internal heat syndrome in the youth differed from that in the middle-aged and elderly(P＜0.01).(2)The tongue and pulse manifestations in IS patients with the leading six detection rates which ranked in descending order of frequency of occurrence were as follows:dull tongue(1 993 cases,37.9%),dark red tongue(1 907 cases,36.3%),thin and white coating(1 885 cases,35.9%),wiry and slippery pulse(1 714 cases,32.6%),white and greasy coating(1 679 cases,32.0%),and wiry and thready pulse(1 609 cases,30.6%).The detection rates of tongue and pulse manifestations such as light red tongue,thin and white coating in the youth group were significantly higher than those in the middle-aged and elderly group,and the detection rates of dark red tongue,and tooth-marked tongue in the middle-aged and elderly group were significantly higher than those in the youth group,the differences all being statistically significant(P＜0.05).The female patients had higher detection rates of dull tongue,thin and white coating,thin and yellow coating,wiry and thready pulse,and deep and thready pulse than male patients,while the male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,yellow and thick-greasy coating,white and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the females,and the differences were all statistically significant(P＜0.05 or P＜0.01).Higher detection rate of thin and white coating was shown in the youth female than that in the youth male,while higher detection rate of wiry and slippery pulse was shown in the youth male than that in the youth female,and the differences were all statistically significant(P＜0.05 or P＜0.01).The middle-aged and elderly female patients had higher detection rates of dull tongue,thin and white coating,wiry and thready pulse,and deep and thready pulse than the middle-aged and elderly male patients,while the middle-aged and elderly male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,white and thick-greasy coating,yellow and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the middle-aged and elderly female patients,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Phlegm-dampness syndrome,qi deficiency syndrome,and yin deficiency syndrome exert a significant effect on IS,and phlegm-dampness syndrome is the most common syndrome type.Factors such as gender and age have influences on the distribution of TCM syndrome in patients with IS.