Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule （补肾活血颗粒， BHG） in treating Parkinson's disease （PD） from the perspecitve of dopamine （DA） homeostasis. MethodsSeventy-two mice were randomly divided into blank group， model group， madopar group and BHG low-， medium- and high-dose groups， with 12 mice in each group. Except for the blank group， all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） for 7 consecutive days to induce a PD model. On the day following the injection， BHG low-， medium- and high-dose groups were administered BHG at doses of 1.25， 2.5， and 5.0 mg/（g·d） by oral gavage， respectively， while the madopar group received madopar tablets at dose of 0.093 8 mg/（g·d） by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test， pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase （TH） in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid （DOPAC） in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 （VMAT2） in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase （ERK）， phosphorylated ERK （p-ERK）， cAMP response element-binding protein （CREB）， phosphorylated CREB （p-CREB） and VMAT2 in striatum. ResultsCompared to the blank group， mice in the model group showed a significant decline in total distance and average speed in the open field test， along with an increase in total resting time； in the pole test， both the time required for the mice to turn completely downward （T-turn） and the total time taken to reach the bottom of the pole （T-total） were prolonged； forelimb grip strength was reduced； in the striatum， the mean optical density of TH， the average fluorescence intensity of VMAT2 protein， and DA content all decreased， while the number of striatal neurons was reduced， and the DOPAC/DA ratio was elevated； the levels of p-ERK/ERK， p-CREB/CREB， and VMAT2 in the striatum significantly decreased （P＜0.01）； transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group， mice in the madopar group and BHG low-， medium- and high-dose groups showed significant improvements in all the above indicators （P＜0.05 or P＜0.01）. Compared to madopar group， the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum （P＜0.05）. Compared to the BHG low-dose group， the BHG high-dose group showed increased total distance and mean velocity， decreased total resting time， T-turn， and T-total， as well as enhanced forelimb grip strength； moreover， the average fluorescence intensity of VMAT2 protein， DA content， p-ERK/ERK， p-CREB/CREB， and VMAT2 levels in the striatum were all significantly elevated （P＜0.05 or P＜0.01）. ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.

Objective:To investigate the effects of medial plantar artery perforator flap in the reconstruction of palmar scar contracture.Methods:This study was a retrospective observational study. From January 2016 to January 2023, 15 patients with palmar scar contracture who met the inclusion criteria were admitted to Guangzhou Peace Orthopedic Hospital, including 12 males and 3 females, aged 15 to 50 years. Before surgery, the Michigan Hand Outcomes Questionnaire (MHQ) scores for the affected hands ranged from 58 to 77, and the total active motion for the affected hands ranged from 190° to 220°. The skin and soft tissue defect area after scar excision on the palmar side of the affected hands was 5.2 cm×3.2 cm to 7.2 cm×6.0 cm. According to the location and area of the wounds, the defects were repaired using either medial plantar artery superficial perforator flaps or combined flaps of the cutaneous perforator of superficial branch of medial plantar artery and medial branch of medial plantar artery deep branch. The area of the harvested flaps was 5.5 cm×3.5 cm to 7.5 cm×6.8 cm. The donor site wounds on the feet were repaired using superficial circumflex iliac artery perforator flaps. Postoperatively, the survivals of the medial plantar artery perforator flaps and superficial circumflex iliac artery perforator flaps were observed. After survival of the flaps, patients were guided for rehabilitation exercises for the affected hands. Regular outpatient follow-up was conducted after surgery to observe the appearance, color, and texture of the medial plantar artery perforator flaps, and the recovery of foot function. At the final follow-up, the two-point discrimination distance of the medial plantar artery perforator flap was measured, the function of the affected hands was evaluated using the trial criteria for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association and the MHQ.Results:Postoperatively, two patients experienced vascular crisis of the medial plantar artery perforator flaps, while the flaps survived after emergency exploration; the medial plantar artery perforator flaps and superficial circumflex iliac artery perforator flaps survived in other patients. Follow-up for 6 to 18 months postoperatively showed that the medial plantar artery perforator flaps had no bulky appearance, similar color and texture to the surrounding skin, and the foot functions such as running and jumping were not affected. At the final follow-up, the two-point discrimination distance of the medial plantar artery perforator flap ranged from 7 to 10 mm, with an average of 8 mm; the affected hand function was rated as excellent in 12 cases and good in 3 cases; the MHQ scores of the affected hand function ranged from 81 to 95, and the patients were satisfied with the postoperative appearance, pain relief, and functional recovery of the affected hand.Conclusions:The medial plantar artery perforator flap is used for the reconstruction of palmar scar contracture. The flap is easy to harvest, and has a high survival rate, resulting in good postoperative recovery of the flap sensation and function of the affected hand, and minimal donor site injury in the foot. It is therefore worthy of clinical promotion.

Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".

There is a close relationship between cardiovascular disease and psychological disease in pathogenesis,treatment and prognosis,but the specific pathological mechanism is not clear.This article explored the understanding of heart failure with anxiety and depression in TCM based on the theory of"deficient qi stagnation",and discussed the pathological mechanism and treatment methods of micro-inflammatory state in heart failure with anxiety and depression in combination with relevant research in both TCM and Western medicine.It is believed that"deficient qi"is the internal factor for the onset of heart failure with anxiety and depression,and"stagnation"is an important pathological condition for the onset.Treatment can be carried out by tonifying qi and blood,nourishing yin and warming yang to replenish"deficient qi",and regulating qi,resolving phlegm,promoting blood circulation,removing blood stasis and promoting diuresis to unblock"stagnation",which can provide theoretical reference for related research and integrated treatment of traditional Chinese and Western medicine on this disease.

There is a close relationship between cardiovascular disease and psychological disease in pathogenesis,treatment and prognosis,but the specific pathological mechanism is not clear.This article explored the understanding of heart failure with anxiety and depression in TCM based on the theory of"deficient qi stagnation",and discussed the pathological mechanism and treatment methods of micro-inflammatory state in heart failure with anxiety and depression in combination with relevant research in both TCM and Western medicine.It is believed that"deficient qi"is the internal factor for the onset of heart failure with anxiety and depression,and"stagnation"is an important pathological condition for the onset.Treatment can be carried out by tonifying qi and blood,nourishing yin and warming yang to replenish"deficient qi",and regulating qi,resolving phlegm,promoting blood circulation,removing blood stasis and promoting diuresis to unblock"stagnation",which can provide theoretical reference for related research and integrated treatment of traditional Chinese and Western medicine on this disease.

Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".

Objective:To investigate the effects of medial plantar artery perforator flap in the reconstruction of palmar scar contracture.Methods:This study was a retrospective observational study. From January 2016 to January 2023, 15 patients with palmar scar contracture who met the inclusion criteria were admitted to Guangzhou Peace Orthopedic Hospital, including 12 males and 3 females, aged 15 to 50 years. Before surgery, the Michigan Hand Outcomes Questionnaire (MHQ) scores for the affected hands ranged from 58 to 77, and the total active motion for the affected hands ranged from 190° to 220°. The skin and soft tissue defect area after scar excision on the palmar side of the affected hands was 5.2 cm×3.2 cm to 7.2 cm×6.0 cm. According to the location and area of the wounds, the defects were repaired using either medial plantar artery superficial perforator flaps or combined flaps of the cutaneous perforator of superficial branch of medial plantar artery and medial branch of medial plantar artery deep branch. The area of the harvested flaps was 5.5 cm×3.5 cm to 7.5 cm×6.8 cm. The donor site wounds on the feet were repaired using superficial circumflex iliac artery perforator flaps. Postoperatively, the survivals of the medial plantar artery perforator flaps and superficial circumflex iliac artery perforator flaps were observed. After survival of the flaps, patients were guided for rehabilitation exercises for the affected hands. Regular outpatient follow-up was conducted after surgery to observe the appearance, color, and texture of the medial plantar artery perforator flaps, and the recovery of foot function. At the final follow-up, the two-point discrimination distance of the medial plantar artery perforator flap was measured, the function of the affected hands was evaluated using the trial criteria for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association and the MHQ.Results:Postoperatively, two patients experienced vascular crisis of the medial plantar artery perforator flaps, while the flaps survived after emergency exploration; the medial plantar artery perforator flaps and superficial circumflex iliac artery perforator flaps survived in other patients. Follow-up for 6 to 18 months postoperatively showed that the medial plantar artery perforator flaps had no bulky appearance, similar color and texture to the surrounding skin, and the foot functions such as running and jumping were not affected. At the final follow-up, the two-point discrimination distance of the medial plantar artery perforator flap ranged from 7 to 10 mm, with an average of 8 mm; the affected hand function was rated as excellent in 12 cases and good in 3 cases; the MHQ scores of the affected hand function ranged from 81 to 95, and the patients were satisfied with the postoperative appearance, pain relief, and functional recovery of the affected hand.Conclusions:The medial plantar artery perforator flap is used for the reconstruction of palmar scar contracture. The flap is easy to harvest, and has a high survival rate, resulting in good postoperative recovery of the flap sensation and function of the affected hand, and minimal donor site injury in the foot. It is therefore worthy of clinical promotion.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.