ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome elements in type 2 diabetes mellitus （T2DM） patients based on maximum body mass index （maxBMI） and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients， extracting age， gender， smoking history， alcohol consumption history， duration of disease， HbA1c level， complications， and TCM syndromes， and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight； patients with maxBMI ≥24 kg/m² were classified into spleen-heat syndrome group， and those with maxBMI ＜24 kg/m² were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients， syndrome elements in spleen-heat patients （1034 cases） were primarily located in the spleen （351 cases， 33.95%）， liver （240 cases， 23.21%）， and stomach （139 cases， 13.44%）， while in consumptive-heat patients （144 cases）， they were concentrated in the spleen （57 cases， 39.58%）， liver （34 cases， 23.61%）， and kidneys （17 cases， 11.81%）； regarding syndrome elements of disease nature， spleen-heat patients were predominantly characterized by qi deficiency （481 cases， 46.52%）， phlegm （353 cases， 22.73%）， and dampness （241 cases， 23.31%）， whereas consumptive-heat patients showed more qi deficiency （84 cases， 58.33%） and yin deficiency （44 cases， 30.56%）. After propensity score matching， 132 cases were included in each group， and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups （P＞0.05）， but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients （P = 0.006）. Regarding the risk of complications， spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients （OR=2.04， P=0.010）， while no significant differences were found between groups in the occurrence of microvascular complications （P＞0.05）. ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm， and a higher risk of developing macrovascular complications compared to consumptive-heat patients.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

Objective: To investigate trends of incidence, mortality, and years of life lost (YLL) rate of lung cancer in cancer registration areas of Guizhou Province from 2017 to 2021, so as to provide references for formulating lung cancer prevention and control strategies and reducing the disease burden of lung cancer. Methods: The qualified lung cancer registration data from cancer registration areas of Guizhou Province from 2017 to 2021 were collected, the crude incidence and mortality of lung cancer were calculated by urban/rural areas, genders and ages. The standardized incidence and standardized mortality was calculated using the age structure of the standard population from the Fifth National Population Census in 2000. YLL was calculated using the standard life table from the Global Burden of Disease Study 2019. The disease burden of lung cancer was assessed using incidence, mortality, and YLL rate, and the trend in the disease burden of lung cancer from 2017 to 2021 was calculated using annual percent change (APC). Results : From 2017 to 2021, the crude incidence, standardized incidence, crude mortality, standardized mortality, YLL and YLL rate in Guizhou Province were 53.13/100 000, 37.58/100 000, 42.77/100 000, 29.44/100 000, 98.19 thousand person-years and 10.95‰, respectively. The standardized incidence and standardized mortality of lung cancer were higher in rural areas than in urban areas (39.45/100 000 vs. 34.23/100 000, 30.68/100 000 vs. 27.18/100 000). The standardized incidence and standardized mortality of lung cancer were higher in males than in females (49.34/100 000 vs. 26.47/100 000, 41.31/100 000 vs. 18.28/100 000). The crude incidence and crude mortality of lung cancer increased with age, peaking in the 80-<85 age group (360.84/100 000) and the ≥85 age group (414.85/100 000), respectively. From 2017 to 2021, the standardized incidence demonstrated downward trends in the total population, urban areas and males (APC=-6.590%, -5.829%, and -6.729%, all P<0.05). The standardized mortality demonstrated downward trends in urban areas and females (APC=-3.710% and -5.378%, both P<0.05). The YLL rate also showed downward trends in urban areas and females (APC=-3.957% and -3.631%, both P<0.05). Conclusions From 2017 to 2021, the overall disease burden of lung cancer in registration areas of Guizhou Province showed a decreasing trend. However, the disease burden remained relatively heavier in rural areas and males, with a relatively gradual change.

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

On August 18,2023,the U.S.Food and Drug Administration(FDA)officially approved Regeneron's Pozelimab-bbfg(Veopoz?)for the treatment of complement factor H-related protein 5 deficiency type protein-losing enteropathy(CHAPLE)disease in children aged 1 and above,as well as adult patients.CHAPLE disease is a rare condition.Pazelimab monoclonal antibody is a recombinant monoclonal antibody(immunoglobulin G4 isotype).This antibody works by binding to the terminal complement protein C5,thereby preventing the cleavage of C5 into C5a(an anaphylatoxin)and C5b,and inhibit the activation of the terminal complement pathway.This article provides an overview of Pozelimab-bbfg,including its pharmacological research,pharmacokinetics,clinical studies,safety profile,and more,to introduce the current state of research and the achievements made with this drug.

Progressive ossifying fibrous dysplasia(FOP)is a rare,hereditary,and progressive connective tissue disease characterized by heterotopic ossification(HO)formation in muscles,joints,tendons,and ligaments,leading to major joint stiffness,limited movement,deformity,and severe disability in patients.In August 2023,Palovarotene was approved by the US Food and Drug Administration(FDA)to reduce the formation of HO in adults and children aged 8 years and above for females and 10 years and above for males with FOP.It is currently the only approved curable drug worldwide.Palovarotene is a selective retinoic acid receptor γ(RAR-γ)agonist that reduces the formation of HO by inhibiting bone morphogenetic protein and SMAD 1/5/8 signaling.The pharmacological study,pharmacokinetics,clinical research,and safety are reviewed to comprehensively introduce Palovarotene.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9％NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P＜0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P＜0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.

68Ga-DOTATOC injection is a radiopharmaceutical agent for positron emission tomography localization of somatostatin receptor positive neuroendocrine tumors(NETs)in adult and pediatric patients.68 Ga-DOTATOC binds to cells that express somatostatin receptors(SSTRs),including malignant neuroendocrine cells that overexpress SSTR2 receptor.Gallium-68 is a radionuclide used in positron emission tomography for tumor diagnosis.This paper introduces its the mechanism of action,pharmacokinetics,usage and dosage,clinical evaluation,safety and use in specific populations.