Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

In the study of kidney ischemia-reperfusion injury, rhabdomyolysis induced kidney injury, hyperuricemia induced kidney injury and other diseases, Diaphragma Juglandis Fructus extract has shown various pharmacological effects such as lowering uric acid, anti-inflammatory, anti-tumor, sedative and sedative effects. It can improve kidney function by reducing inflammatory response, inhibiting oxidative stress, regulating related enzyme activity and other mechanisms. At the same time, Diaphragma Juglandis Fructus extract also has hypoglycemic and lipid-lowering effects, which can regulate glucose and lipid metabolism, inhibit inflammatory reaction, and reduce oxidative stress. It has potential application prospects in the treatment of diabetes nephropathy. At present, current research is mostly focused on animal and cellular experiment levels. Although certain achievements have been made, further clinical research is still needed to clarify its effectiveness and safety in the human body, and to further explore the active components to promote its application in the treatment of kidney diseases in clinical practice.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Objective:To analyze clinical data related to mineral and bone disorder(MBD)in elderly maintenance hemodialysis patients and provide a basis for the development of precise clinical treatment strategies.Methods:A total of 267 patients receiving regular hemodialysis at Beijing Huairou Hospital and Huairou District Hospital of Traditional Chinese Medicine between April 2022 and June 2022 were selected and divided into an elderly group(age≥60 years)with 129 patients and a younger group(age<60 years)with 138 patients.Patients' general information, medication use, and laboratory data including routine blood work, blood calcium, blood phosphorus, and intact parathyroid hormone were collected, and a survey questionnaire was conducted to collect data on hyperphosphatemia patients' knowledge about diet and medication use.Differences in the rate of meeting calcium and phosphorus target ranges, medication use, and questionnaire scores were compared between patients in the two groups.Results:(1)The rates of controlled Ca(2.3±0.2)mmol/L, P(1.9±0.6)mmol/L and iPTH[213.5(93.5, 359.9)ng/L]levels in the elderly group were 65.1%(84/129), 43.4%(56/129)and 51.2%(66/129), respectively.There were no statistically significant differences compared with the younger group(all P>0.05). The prevalence of hyperphosphatemia in the elderly group(66/129, 51.2%)was lower than that in the younger group(90/138, 65.2%)( χ2=5.422, P=0.020). (2)Compared with the younger group, the elderly group had lower levels of serum creatinine[(796.6±225.2)μmol/L vs.(1025.6±281.4)μmol/L], uric acid[(416.9±97.0)μmol/L vs.(445.0±106.6)μmol/L], albumin[(37.9±2.9)g/L vs.(39.0±3.0)g/L]and serum phosphorus[(1.9±0.6)mmol/L vs.(2.1±0.6)mmol/l]( t=7.289, 2.238, 2.941, 2.820, P<0.05), and a higher blood glucose level[6.9(5.2, 9.8)mmol/L vs.6.1(4.9, 8.2)mmol/l, Z=2.314, P=0.015]. (3)Compared with the younger group, the elderly group had significantly lower utilization rates of calcium-free phosphate binders[12.4%(16/129) vs.23.9%(33/138)]and calcimimetics[2.3%(3/129) vs.10.9%(15/138)]( χ2=5.895, 7.742, P<0.05, respectively). (4)Compared with the younger group, the elderly group had a lower total questionnaire score(36.8±6.6 vs.39.5±6.0), a lower hyperphosphatemia knowledge score(4.7±3.1 vs.6.0±2.8), a lower diet knowledge score(2.8±2.2 vs.4.0±1.9)and a lower medication knowledge score(2.1±1.9 vs.3.1±1.8, t=3.442, 3.694, 4.677, 4.398, respectively, P<0.05 for all), but had a higher compliance score(17.3±1.9 vs.16.4±2.4, t=3.390, P=0.001). (5)Multivariate Logistic regression analysis indicated that pre-dialysis blood urea nitrogen( OR=1.082, 95% CI: 1.011-1.159, P=0.024)and serum creatinine( OR=1.002, 95% CI: 1.001-1.005, P=0.036)were independent predictors of hyperphosphatemia in elderly hemodialysis patients. Conclusions:Compared with the younger group, the serum albumin and phosphorus levels were lower, the utilization rates of calcium-free phosphate binders and calcimimetics were lower, and the total score of the hyperphosphatemia questionnaire was also lower in the elderly group.However, the compliance score was significantly higher in the elderly group.We should focus on the relevant weak links to bolster diet education and medication management for elderly hemodialysis patients.

Inflammatory diseases are key contributors to high mortality globally and adversely affect the quality of life. Current treatments include corticosteroids or nonsteroidal anti-inflammatories that may cause systemic toxicity and biologics that may increase the risk of infection. Composite nanoparticles that bear not only the drug payload but also targeting ligands for delivery to inflammation sites at lowered systemic toxicity are established in the nanomedicine field, but their relatively large size often leads to systemic clearance. Metal-based nanoparticles with intrinsic anti-inflammatory properties represent attractive alternatives. They are not only designed to be compact for crossing biological barriers (with the nanoparticle serving as a dual carrier and drug), but also support label-free tracking of their interactions with cells. The review commences with an outline of the common inflammatory diseases, inflammatory pathways involved, and conventional drug-loaded nanoparticles for anti-inflammation. Next, the review features the emerging applications of self-therapeutic metal-based nanoparticles (e.g., gold, coper oxide, platinum, ceria, and zinc oxide) for managing inflammatory diseases in animals over the past three years, focusing on therapeutic outcomes and anti-inflammatory mechanisms. The review concludes with an outlook on the biodistribution, long-term toxicity, and clinical translation of self-therapeutic metal-based nanoparticles.

Objective:To evaluate the value of p16 INK4a detected by p16 INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods:Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16 INK4a technology, among them, 902 cases were offered p16 INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16 INK4a staining. Participants with complete LCT examination, HR-HPV test, p16 INK4a staining and histopathological examination results were included in this study. The performance of p16 INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) +] were analyzed. Results:(1) One-thousand and ninety-seven cases with complete data of p16 INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ) + and 34 cases of HSIL (CIN Ⅲ) + were detected. The positive rate of p16 INK4a in HSIL (CIN Ⅱ) + was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16 INK4a as primary screening for HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16 INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16 INK4a for detecting HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + were higher than that of LCT alone or adjunctive HR-HPV ( P<0.01), while the sensitivity were similar ( P>0.05). (4) p16 INK4a staining as secondary screening: p16 INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16 INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions:For primary screening, p16 INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16 INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16 INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.

Objective:To investigate the use of p16 INK4a immuno-stained cytology as the primary screening for cervical cancer prevention. Methods:From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16 INK4a co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16 INK4a test. The performance of p16 INK4a for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16 INK4a were evaluated. Results:The positive rates of HPV test, p16 INK4a co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16 INK4a test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16 INK4a and TCT/HPV test ( P>0.05). The Kappa value of the 2 cytopathologists in interpreting p16 INK4a and TCT was 0.944 and 0.425, respectively ( P<0.05). Conclusions:p16 INK4a for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists′ interpretation of p16 INK4a is small. Therefore, p16 INK4a can be used as a new cervical cancer screen method for its better diagnostic performance.

Objective To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16, 18 with cytology [≥atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+; including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions (r=-0.617, P=0.000), and significant different among normal cervix,LSIL and HSIL+(35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F=25.537, P=0.000). There was no correlation between Ct value of HPV 18 and cervical lesions (r=-0.021, P=0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix , HSIL+and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F=5.087, P=0.007). Among them, LSIL and HSIL+ were significantly lower than normal cervix (P<0.05), but there was no significant difference between LSIL and HSIL+(P>0.05). Conclusion The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis.

Objective To investigate the value of lung ultrasound scores ( LUS ) combined with echocardiography for evaluation of the state of preterm neonatal respiratory distress syndrome ( RDS ). Methods Lung ultrasound and echocardiography were conducted on 43 preterm newborns with RDS. The echocardiographic parameter included the area and velocity of tricuspid regurgitation, patent ductus arteriosus ( PDA ) and pulmonary artery systolic pressure ( PASP ). Correlational analyses of LUS and PASP,or X-ray grading were conducted. LUS difference was compared between the groups with PDA and without PDA. Results ① There was positive correlations between LUS and PASP ( r ＝ 0.647, P ＜0.05),LUS and X-ray grade ( r ＝0.770, P ＜0.05). ②LUS was significant different in different X-ray grade( F ＝ 31.460, P ＜ 0.05). ③ Significant difference was found between the groups with PDA and without PDA( t ＝3.08, P ＜0.05). Conclusions LUS combined with echocardiography can be used as an effective method for early diagnosis,condition assessment and prognosis of RDS,and it is more direct,fast and without radiation.